Effects of zinc, copper, and manganese supplementation of high-concentrate ration on gastrointestinal absorption of copper and manganese in Holstein calves. Sixteen Holstein bull calves were fed a high-concentrate ratio supplemented with zinc, copper, and manganese, alone or in combination, for 10 wk. After 6 days of preliminary feeding of chromic oxide, fecal grab-samples were collected for 6 days. Calves were slaughtered, and samples of the contents of the reticulo-rumen, omasum, abomasum, small intestine, cecum, and large intestine were analyzed for chromic oxide, copper, and manganese. Absorption along the gastrointestinal tract, measured by comparison of one segment with the previous segment, indicated net secretion of copper in the abomasum but net absorption from the rest of the tract. The exception was that net secretion into the reticulo-rumen was associated with low dietary copper. Net secretion of manganese was mainly in the small intestine and cecum in all treatments. A higher proportion of copper apparently was absorbed when this mineral was supplemented in the ration. However, absorption of manganese was decreased slightly when manganese was supplemented in the ration. Reabsorption of manganese in the large intestine was probably greater than that of copper.


Fatty acids of vegetative cells and spores of Bacillus licheniformis. Lipids were extracted from vegetative cells and spores of Bacillus licheniformis. Vegetative cells were grown in nutrient broth and spores on nutrient agar. Total lipid approximated 2.89% of the dry weight of vegetative cells and 2.09% of the dry weight of spores. The fatty acids were prepared as methyl esters and analyzed by gas chromatography and mass spectrometry. There were six fatty acids in concentrations greater than 5% of the total lipid in both spores and vegetative cells, but only palmitic acid was common to both. Fatty acids from vegetative cells in quantities of 5% or more of the total lipid material were lauric, myristic, palmitic, palmitoleic, and linoleic acids. Fatty acids from spores in concentrations greater than 5% of the total lipid were isopentadecylic, palmitic, Carbon-17 iso, and three other long or branched chain fatty acids which were not identified. Spores contained more long and branched chain fatty acids with odd numbers of carbon atoms than did vegetative cells.


Hydroxyproline in serum as a homeostatic index for calcium in cattle. Hydroxyproline, calcium, magnesium, phosphorus, and alkaline phosphatase values were determined in serum over 24 h in Holstein cows. The cows represented two age groups and three percents of diet calcium. Hydroxyproline followed a cyclic pattern dipping at 0800 and 1600 h after milking at 0500 and 1530 h. Phosphorus showed a 24 h rhythm peaking at 1600 h. No other time effects were demonstrated. Hydroxyproline and alkaline phosphatase were both lower in the older cows, indicating a decreased calcium mobilization from bone with age. There was a correlation coefficient of only .20 between serum calcium and hydroxyproline. The calcium concentration in serum was maintained within a narrow range presumably as a result of homeostatic mechanisms involving bone resorption, i.e. the release of calcium and hydroxyproline may indicate the degree of homeostasis required to maintain serum calcium.


Peripheral plasma determinations of prostaglandin E in asthmatics. Prostaglandins, unsaturated fatty acid derivatives with diversified pharmacologic activity, have recently been implicated in the pathophysiology of reversible airway disease. This study attempted to elucidate baseline prostaglandin E (PGE) plasma levels in asthmatics and the change in these levels after stimulation by a beta-adrenergic agent. Fourteen stable, ambulant patients with reversible airway disease and 28 nonatopic control subjects were studied. All had baseline PGE levels performed. The asthmatics were asked to abstain from all medication for 10 hr prior to evaluation. After baseline evaluation consisting of plasma PGE determination, pulmonary function test, blood pressure, and heart rate, 375 mug of aerosolized terbutaline sulfate was administered to 8 of the asthmatics plus 4 of the nonatopic control subjects; the above measurements were repeated at 15, 30, and 60 min after administration. There was a statistically significant difference in baseline plasma PGE levels between the asthmatics (PGE = 432 +/- 81) and the nonatopic control subjects (PGE = 89 +/- 9) (p less than 0.002). Following terbutaline administration, there was no significant change observed in PGE levels in asthmatic or in control individuals (asthmatics: 0 min, 570, 15 min, 513, 30 min, 514, 60 min, 608; normal subjects: 0 min, 138, 15 min, 137, 30 min, 143, 60 min, 214). In summary, we observed a significant difference in baseline PGE levels between asthmatic and nonatopic control persons. No change, however, was noted in PGE levels after beta-adrenergic receptor stimulation. This observation is consistent with the current hypothesis that beta-adrenergic agents act independently of prostaglandins to increase adenyl cyclase and modify bronchiole smooth muscle tone.


Allergens in bee venom. I. Separation and identification of the major allergens. Honeybee venom was separated into seven fractions by gel filtration on Sephadex G-75. Allergenic activities of these fractions were assessed by the paper disc radioallergosorbent test (RAST) with a panel of sera from 24 individuals who had systemic reactions to bee stings, 7 who had large local reactions, and 10 control subjects who had reactions of 5 cm or less following bee stings. Three fractions were identified by enzyme or direct hemolytic activity. Twenty-nine of 31 sera from patients having either systemic or large local reactions to bee stings were positive when radioallergosorbent tested with whole bee venom; 22 were positive to phospholipase A, and 28 were positive to both fractions 1 and 2. Thirteen sera combined most strongly with fraction 1, 12 sera most strongly with fraction 2, hyaluronidase, and three sera about equally with fractions 1, 2, and 3. Reactions with other fractions were much weaker. Fractions 1 and 2 were potent inhibitors of RAST with whole venom in the sera reacting most strongly with fractions 1 or 2, respectively. Fraction 3, phospholipase A, and commercial bee venom phospholipase A were significantly less potent inhibitors with the sera tested. In the cases in which IgE antibody bindings to fractions 1, 2, and 3 were of similar magnitude, inhibitions of RAST using the various fractions both on the discs and as inhibitors demonstrated substantial cross-reactivity between the fractions. These results strongly indicate that by using RAST with human sera from bee sting-sensitive individuals, fraction 1, the high molecular materials, and fraction 2, hyaluronidase, are the major allergens in honeybee venom. Phospholipase A appears to be of secondary importance.


The effects of topical saline and isoproterenol on nasal airway resistance. Following determination of baseline nasal airway resistance (NAR) in human subjects, phosphate-buffered saline (PBS) was aerosolized into each nostril and NAR measurements repeated 8 times in 15 minutes. The mean maximal NAR increase in 102 subjects was 22.5% (SD +/- 24.5%) with no significant difference between atopic and nonatopic persons. Hay fever patients did not show significantly increased responsiveness to PBS while symptomatic. During 242 repeat challenges with PBS in 67 asymptomatic subjects, NAR increased over 50% in 24 tests. Following a series of 6 PBS challenges at 15-minute intervals, 10 of 71 subjects had more than a 100% increase in NAR over initial baseline values. Administration of PBS on cotton pledgets, pipetting PBS into the nose, or even just inserting a nasal speculum produced greater increases in NAR than the usual aerosol method. Intranasal atropine effectively blocked PBS-induced increases in NAR, suggesting parasympathetic stimulation as a mechanism. Isoproterenol increased NAR over 100% in 27 of 53 subjects, with no significant difference among rhinitic, asthmatic, and nonatopic individuals. This effect was inhibited by propranolol. Isoproterenol administration to 12 ragweed-sensitive subjects 15 minutes prior to ragweed challenge produced a variable inhibition in NAR responses or no protection at all. Thus the direct effects of isoproterenol on the nasal vasculature tend to outweigh those expected from inhibition of mediator release under the conditions of this study.


Evaluation of exercise-induced bronchospasm in the adult asthmatic. It has been shown that most asthmatics respond to exercise with bronchospasm. This study was undertaken to develop a safe and reliable method for quantifying exercise-induced bronchospasm in the asthmatic adult. Five normal adult volunteers and 12 stable asthmatics were exercised to 80% of their predicted maximal heart rate according to a multistage branching treadmill protocol. Their responses in terms of forced expiratory volume in 1 sec (FEV1) and maximum midexpriatory flow rate (MMEFR) at 5, 15, and 30 min after exercise were assessed, while standing, with a Jones Pulmonar II waterless spirometer. This submaximal stress test was chosen because 80% of predicted maximal heart rate could be obtained by all individuals and allowed the asthmatics to exercise long enough for inducible bronchospasm to occur. Audible wheezing was induced in 100% of the asthmatics and in none of the nonasthmatics. In the normal individuals, FEV1 and MMEFR increased signficantly during the postexercise period. When compared to normal subjects, the 12 asthmatic patients demonstrated a significant reduction in FEV1 an MMEFR (deltaFEV1 : 5 min, -300; 15 min, -304; o9 min, -208 ml; -18%, -17%, and -15%; deltaMMEFR: 5 min, -15; 15 min, -9; 30 min, -1L/M; -23%, -18%, and -6%) (p less than 0.01). The use of a rigidly controlled exercise stress with a cardiovascular endpoint in the measurement of FEV1 and MMEFR in the postexercise period appears to be a useful tool in assessing the presence and severity of exercise-induced bronchospasm in the adult asthmatic.


Measurement of plasma prostaglandins during exercise-induced bronchospasm. Bronchospasm following exercise is a phenomenon which occurs in most patients with reversible airway disease. The pathophysiologic mechanism leading to this bronchoconstriction with exercise has not yet been defined. Recently, prostaglandins have been implicated in the etiology of asthma. The purpose of this investigation was to determine changes in plasma prostaglandins occurring during exercise-induced asthma. Eight ambulant asthmatics were chosen for baseline pulmonary spirometry and peripheral venous blood prostaglandin E and F levels. The asthmatics were then exercised to 80% of their age-predicted maximal heart rate via a multistage branching treadmill protocol. At 5, 15, and 30 min following exercise, pulmonary spirometry was again performed and peripheral venous blood collected at the indicated times. Clinical bronchospasm as characterized by audible wheezing and greater than 15% decrease in FEV1 and MMEFR was obtained in all of the asthmatics. Peripheral PGE and PGF2alpha determinations following this exercise protocol were not altered significantly: (PGE: 0 min, 238; 5 min, 185; 15 min, 248; 30 min, 256 pg/ml); (PGF2alpha: 0 min, 50; 5 min, 24; 15 min, 25; 30 min, 17 pg/ml) (p less than 0.1). In summary, no significant change in peripheral blood prostaglandin E and F2alpha levels as determined by radioimmunoassay was noted at the time of exercise-induced bronchospasm.


Dietary interviewing by computer. An experimental approach to counseling. A computer-based dietary counseling system was tested by sixty-four volunteers from the Boston area. Most of the patients seemed to benefit from their interaction with the computer, and the two participating nutritionists frequently found that the program was useful as an antecedent to their own one-to-one sessions with the patients.


Comprehensive evaluation of fatty acids in foods. IX. Fowl. An extensive survey of the post-1960 literature on the lipids of fowl has been completed. This review shows that the total lipid content of chicken tissues increases with age. The fatty acid composition of both chicken and turkey tissues reflects the fatty acid composition of the dietary fat. The fatty acid composition data for dark meat, light meat, or skin of all classes of chicken --broiler-fryer, roaster, and stewing hen--raised on diets equivalent to commercial feed were combined into single tissue-type fatty acid profiles. Similar profiles were also established for roaster-fryer turkey, young tom turkey, and young hen turkey. Breed, sex, and environmental temperature showed only minor effects on the tissue fatty acid compositions. Young chicken flesh contains less fat than that of stewing hens, turkeys, and other fowl, which all have approximately equal total fat content. White meat of chicken and turkey contains the least amount of fat, and the skin of all birds contained the largest amount, duck and goose skin containing the greatest of all. Tables of the total fat and fatty acid composition of tissue and tissue composites of fowl are given. Studies on chicken and turkey tissues were sufficiently numerous that the computed fatty acid compositions in the tables are considered reliable representation of market birds. Data for goose, duck, partridge, pheasant, pigeon, and quail were computed from sparse information and should be viewedas provisional guides.


Fate of DDT and parathion in grapes processed into arak, an alcoholic beverage. Arak, the national alcoholic drink in Lebanon, was prepared from grapes to which either DDT or parathion had been added. Samples of the nine fractions produced from the fermentation and distillation steps were analyzed for DDT and parathion and their respective metabolites. DDT degraded to DDD during the fermentation step resulting in a sharp decrease in DDT level. The two distillation steps contributed to a further decrease in the DDT level so that the final product contained less than 2% of the amount found in the fresh grape juice. Although the concentration of DDD increased sharply during fermentation, it also decreased to a negligible level during the subsequent distillation procedure. Parathion was more stable than DDT during the fermentation and first distillation steps. However, the second distillation process caused a sharp decline in its level and the Arak contained only about 6% of the residues present in the fresh juice, paranithophenol being the only metabolite detected.


Contributions to ecological chemistry CXII1. Balance of conversion of buturon-14C in wheat under outdoor conditions. The urea herbicide buturon (N-[p-chlorophenyl]-N'-methyl-N'-isobutinyl-urea), 14C-labeled, was sprayed on winter wheat as an aqueous formulation (2.98 kg/ha) under outdoor conditions. Upon harvest (three months after application), a total of 49.2% of the applied radiocarbon was recovered: 2.0% in the plants, 46.9% in the soil, and 0.3% in the leaching water (depth greater than 50 cm); less than 0.1% was in the grains (0.464 ppm). Only about half of the radioactivity present in plants could be recovered under mild extraction conditions; about half of this was unchanged buturon. In straw and husk extracts, the following metabolites were identified by gaschromatography/mass spectrometry:N-(p-chlorophenyl)-N-methyl-O-methyl-carbamate (metabolite I), N-phenyl-N'-formyl-urea (metabolite II), two unstable metabolites giving (p-chlorophenyl)-isocyanate upon purification (metabolites III and IV), N-(p-chlorophenyl)-N'-methyl-N'-isobutenylol-urea (metabolite V), p-chloroformanilide (metabolite VI) and biologically bound p-chloroaniline (metabolite VII). In the root and basal stem extract, the following metabolites were identified by gas chromatography/mass spectrometry: N-(p-chlorophenyl)-O-methyl-carbamate (metabolite VIII) and N-(p-chlorophenyl)-N'-methyl-urea (metabolite IX).


Movement and metabolism of S-benzyl O,O-diisopropyl phosphorothiolate (Kitazin P) and O-ethyl S,S-diphenyl phosphorodithiolate (edifenphos) in various types of soils. Movement and Metabolism of 32P and 35S-double labeled Kitazin P (S-benzyl O,O-diisopropyl phosphorothiolate) and 35S-labeled edifenphos (O-ethyl S,S-diphenyl phosphorodithiolate) were examined with three types of soils, sandy loam, alluvial clay loam, and volcanic ash loam. Vertical movement of both the compounds in soil column was different with soil types, and the order of mobility in soil column was as follows: sandy loam greater than alluvial clay loam greater than volcanic ash loam. Persistence of edifenphos in soil was shorter than that of Kitazin P. Main degradation products at the initial stage of metabolism were S,S,S-triphenyl phosphorotrithiolate, O,O-diethyl S-phenyl phosphorothiolate, S-phenyl dihydrogen phosphorothiolate and diphenyl disulfide in edifenphos and O,O-diisopropyl hydorgen phosphorothioate in Kitazin P. Sulfur atom of Kitazin P was found in sulfuric acid at a minor level through dibenzyl disulfide and toluene-alpha-sulfonic acid, and that of edifenphos was converted to sulfuric acid through diphenyl disulfide and benzenesulfonic acid. Kitazin P under flooded condition of alluvial clay loam was slightly more persistent as compared with upland condition. Sterilized condition of Kitazin P did not cause any appreciable degradation throughout the experimental period, but such condition did not necessarily prevent the degradation of edifenphos.


Variations in fluorescence characteristics of intact human crystalline lens segments as a function of age. Fluorescence spectra of human lenses were examined as a function of age. The relative intensity in the blue-green area was red shifted with age. Absorption and scatter produce a substantial contribution to this shift. Some change, however, was the result of a true fluorescence intensity shift. In the lower blue region a true independent red shift was found in the nucleus, but not in the cortex. In the upper blue region, true red shift in the nucleus was not significant with fluorescence excited at 400 nm but was significant with fluorescence excited at 375 nm; the shift was well defined in the cortex. This pattern is consistent with age-related accumulation of multiple fluorogens or fluorogen precursors in the lens with relative concentration differences in nucleus and cortex.


Gerontological data of C57BL/6J mice. II. Changes in blood cell counts in the course of natural aging. A group of 1,052 C578L/6J mice -- 296 males and 756 females - was kept under well defined, clean, conventional conditions from the age of 6 weeks until natural death. At regular time intervals several hematological values were examined from 50 to 60 randomly selected animals of each sex and statistically evaluated. The hematological investigations did not reveal any important sex-related differences. A significant gradual decrease of the RBC counts and hemoglobin content was observed during the life-span. Lymphocyte and total WBC counts were subject to considerable variation. They decreased in the first two-thirds of life and increased in the last third. Neutrophils remained rather stable and exhibited an increasing trend in the higher age. The relative level of lymphocytes decreased signficantly in favour of neutrophils during natural aging.


A clinical comparison of tests of organicity in elderly patients. The quantification and standardization of observations of clinically significant organicity in the elderly is possible through the administration of specific cognitive tests. In this study, four organicity tests were evaluated on a geriatric medical/surgical patient group, with the SPMSQ yielding the best correlation with a clinical diagnosis of organicity. The SPMSQ is also recommended for its ease of administration, brevity, quantitative output, and straight-forward interpretation. The FHT produces an increment of improvement in the identification of organic groups, thus serving as a useful second test. The MSQ, while longer and slightly more complex, is roughly equivalent to the SPMSQ. The MFD test, the most lengthy and complex of the four instruments used, did not add sufficient additional information for this sample to warrant its inclusion in a testing regimen. Accurate diagnosis is critical for the geriatric patient if excessive morbidity and mortality are to be avoided, and unnecessarily long hospital stays are to be reduced. The availability of a short, easily administered test like the SPMSQ can effectively improve the assessment of the elderly patient at little additional cost to the clinician.


The effects of age and genotype upon the jaw-jerk reflex in inbred mice. The threshold of the jaw-jerk reflex to electrical stimulation of the hard palate was measured in a cross-sectional design using C57BL/6J and DBA/2J mice at 2, 8, 20, 25, and 30 mo of age, in order to assess CNS sensitivity as a function of increasing age. The thresholds of DBA/2J mice were higher than those of C57BL/6J mice at all ages tested. No age-related changes in threshold were observed in mice of either strain.


Relations of age and personality dimensions to cognitive ability factors. The relation between three cognitive ability factors - Information Processing Ability (IPA), Manual Dexterity (MD), and Pattern Analysis Capability (PAC) - and three personality dimensions - Anxiety, Extraversion, and Openness to Experience - were examined in three age groups. Subjects were 969 male volunteers ranging in age from 25 to 82. Subjects high in anixety scored lower on all three cognitive factors; subjects open to experience scored higher on IPA and PAC; and introverted subjects scored higher on PAC. Most of these effects remained when the education and socio-economic status were held constant in covariance analyses. Older subjects performed less well than younger ones on MD and PAC, but not on IPA. While personality has some influence on cognitive performance, the declines with age in performance on some cognitive tasks are not mediated by personality.


Solution shift performance in the elderly. Seventy-two elderly adults were presented a concept problem which varied as a function of type of solution shift (reversal or nonreversal) and stimulus materials (compact designs, distributed designs, or distributed foods). Both trials to criterion and postshift error patterns were analyzed. Results indicated that stimulus materials affected postshift performance and that the elderly do respond in a dimensional fashion under some circumstances. Examination of individual protocols revealed that a rigidity notion would not account for the difficulty the elderly experienced when solution was shifted. Several alternative explanations were offered for the failure of many volunteers to solve the postshift problem.


Categorization behavior in aging subjects. Age changes in categorization and conceptual styles were studied using an object-sorting task in 276 subjects representing 7 age groups: 5, 6, 7, 19-21, 60-69. 70-79, and 80-89. Significant age effects (p less than 01) were found in the analysis of variance for four of six measures; there were no significant sex or interaction effects. Strong quadratic trends were found for number of ungrouped objects, % relational-thematic responses, and % categorical-inferential responses; oldest groups' responses were similar to children's. A linear trend was found for number of groups. There was no significant age effect for category breadth. Use of descriptive-analytic categories by the elderly was negligible compared to younger subjects.


Attitudes toward aging as a function of in-service training and practitioner age. Age differences in attitudes toward aging were investigated as a function of a 3-hour training program with 322 women (18-74 years) from various geriatric health care and social service contexts. Using a quasi-experimental pre- and posttest design, sites were randomly divided into initial experimental and control groups, with all control participants receiving training following the research program. Results indicated few instances of unfavorable attitudes toward aging in any age group, with younger women evidencing less cynicism toward aging, less social distance from the aged, and slightly less stereotyping. Training appeared to result in less cynicism, stronger endorsements of family and public responsibility, and slightly greater anxiety. No Age X Pretest/Posttest interactions were found. The results are discussed in terms of their implications for service provider-client interaction, the correspondence of attitudinal and behavioral change, and appropriate instruments for assessing program impact.


A re-examination of widowhood and morale. Previous research has suggested widowed status to be associated with lower morale or life satisfaction. The effects of marital status on morale relative to five covariates (health, income, age, family interaction, and employment status) were examined with 232 widowed and 363 married women aged 45-74, drawn in a multistage stratified area probability sample of Los Angeles County. Analysis of covariance was utilized with a six-item, factor analyzed measure of morale. Parallel analyses were performed for each of three ethnic groups (blacks, Mexican-American, and white) to examine specific ethnic patterns. In the total sample, poor health was associated with significantly lower morale among widowed than among married women. The analysis with age showed the widowed group catching up and surpassing their married peers on morale at higher ages. Controlling for income and employment status eliminated differences between the marital status groups on morale scores. Higher family interaction was positively associated with morale in both groups, but married women were consistently higher on morale regardless of level of interaction. Most ethnic differences were not significant, but family interaction appeared to be crucial among Mexican-American widows. The findings suggest that lower morale scores found among the widowed may be partly attributable to other factors commonly associated with this status and not due to the role of widowhood per se.


Report from the National Institute on Aging: the research grant support mechanism. Most NIH support of research on aging has been in the area of the biomedical sciences, followed by behavioral and social sciences. Research project and program project grants are the primary mechanisms available to the NIA for support of research on aging. The grant process for aging research begins with preparation and review at the applicant institution. The process of review at NIH proceeds from referral to an intitial review group for peer review and NIA for possible funding, NIA staff review, the National Adivisory Council on Aging review, and concludes with NIA funding action. The primary mode of applicant appeal of a negative decision by NIA on an application is reapplication.


[Possible immunologic factors in natural selection of the sexes]. The foetal graft is protected from immunological rejection by the trophoblastic barrier, antigenically neutral. A deficiency of this protective barrier puts the highly antigenic egg contents in direct contact with the maternal organism. The formation of maternal antibodies, and the rejection reaction of the egg graft due to it, probabally explains certain miscarriages. We think that the male fetus must, in these cases, be more antigenic with regard to the graft carrying maternal organism, than the female fetus. A study of 222 pregnancies, with repeated spontaneous miscarriages confirms the clear preponderance of girls, among the non-premature and well-formed children born, and the efficiency of H.C.G. in protecting threatened pregnancies with male fetus.


The cytochemical demonstration of prostatic acid phosphatase using a new substrate, phosphorylcholine. Prostatic acid phosphatase (PAP), an acid phosphatase specific to the prostate gland, is demonstrated cytochemically for both light and electron microscopy with a new substrate phosphorylcholine. Lead ion is used as capture agent for liberated phosphate ion in a modified Gomori medium. PAP is demonstrated in the tubuloaveolar epithelial secretory cells of the rat ventral prostate gland. In the apical portion of the cell it is found in secretory granules and in the matrix of multivescular bodies. In the Golgi area it is localized in Golgi cisternae, Golgi related vacuoles and multivescular bodies. Evidence is presented that PAP is not a lysosomal enzyme, as are other acid phosphatases, and that phosphorylcholine is a highly specific substrate for PAP. As based on the role of pentavalent nitrogen on substrate structure, it is apparent that PAP is to other acid phosphatases what the cholinesterases are to other esterases.


[Leukocyte reactions "in vitro" to human spermatozoa in infertile females]. Leucocyte migration test was done in 55 couples facing fertility problems for detection of antispermatozoal cellular hypersensitivity. In 29 cases out of 55, the sterility was unexplained and in 26 cases out of 55, various infertility factors were found. In this study, wife's leucocytes separated on Ficoll-Urografin gradient were incubated (4.10(6) per capillary) with washed fresh husband's spermatozoa suspended at 7.10(6)/ml in M 199 and 20 p. 100 fetal bovine serum. The results were read after 18h. Two kinds of migration inhibition were found: 1) Specific wives leucocyte migration inhibition in 4 out of 55 cases, all of them unexplained infertility cases. 2) Leucocyte migration inhibition not related to wife's immunity state and possibly due to a direct effect of a toxic or inhibitory property of some husband's spermatozoa in 22 out of 55 cases, 11/19 cases with known male factors, and 11/36 cases without any male factor. In the follow up, only 1 woman out of the 22 couples with husband's spermatozoal inhibitory factor was pregnant later, while in the group of 29 women in which normal leucocyte spreading was found, 8 women conceived later. No woman out of the 4 suspected of antispermatozoal delayed hypersensitivity have conceived. Attention must be paid to the possible role of delayed hypersensitivity to sperm in unexplained infertility and also to the occurrence of spermatozoal toxic factor and its possible implications on human infertility.


Variation in the autoradiographic technique: I. Emulsion-developer combinations assessed by photometric measurement of single silver grains. Five commonly used developers (Acufine, Rodinal, Dektol, D19 and Microdol X) and two popular nuclear gel emulsions (Kodak NTB-2 and Ilford L4) were tested in combinations for adequacy of development characteristics and the distribution of silver particle (grain) size measured by means of a reflectance microphotometer. All developer-emulsion combinations had some range of development time during which maximum development was accomplished with no occurrence of background grains, with the exceptions of the combinations of NTB2-Acufine and NTB2-D19. Ilford L4 emulsion obtained the narrowest grain size distribution with Rodinal and Acufine, followed by Dektol, and D19. The narrowest size distribution for Kodak NTB2 emulsion was achieved with D19 followed by Acufine, Dektol and Rodinal. Microdol-X had undesirable effects on the integrity of the individual grains of both emulsions. The criteria are discussed for selecting the most advantageous emulsion-developer system for the particular mode of evaluation (visual, photometric, television camera) to be applied to the finished autoradiographic specimens.


[Toxoplasmosis and interruption of pregnancy. Results of 21 parasitologic examinations]. Mouse inoculations were carried out after 21 pregnancies had been terminated for acquired toxoplasmosis. Only one positive result was obtained.


A comparative ultrastructural localization of concanavalin A, wheat germ and Ricinus communis on glomeruli of normal rat kidney. Three lectins, concanavalin A, peroxidase labeled wheat germ and peroxidase labeled Ricinus communis have been utilized to determine the localization of various saccharide determinants in the glomerulus of the normal rat kidney. In order to obtain a homogeneous penetration of the lectins throughout the whole section, various technical parameters were studied. Only with concanavalin A, a diffuse labeling of the endoplasmic reticulum was obtained. With the three lectins, the basement membrane, mesangial matrix and the cell coat of the three cell types in the glomerulus were labeled. Differences in the labeling of the capillary wall were also noted.


[Perineal echotomography. A new method of objective measurement of the cervix]. Perineal echotomography is a method for measuring the dilatation of the cervix and is a good measure of the cervix during pregnancy. It permits visualization of the bag of waters, the presentation of the fetus and of the low-lying placenta.


Factors affecting the incomes of men and women physicians: an exploratory analysis. Income differences between men and women physicians are analyzed using data from the Americal Medical Association's 1973 Eighth Periodic Survey of Physicians. While women tend to possess less favorable professional characteristics in terms of income-earning potential, the returns to many characteristics associated with higher incomes are greater for women than for men. Additional evidence on differences in weekly hours worked is presented in an effort to explain the lower incomes of women doctors.


The demand for dental care: a study of consumption and household production. Within the context of a Becker-type consumer's choice model, this paper reports an empirical study of the demand for dental care for approximately 1,000 households. The unique feature of the study is that waiting time and travel time as well as price and other traditional economic variables are entered into the regression analysis. Generally, the results confirm our expectations derived from theory, but elasticities with respect to all of the above-mentioned determinants of demand were small. In addition, some of the subtle predictions of the theory could not be confirmed.


[Attempt at evaluation of the risk of mortality in utero]. An analysis was made of the obstetric history of 1,360 patients who were delivered in 1971. It involved 3,185 pregnancies. The aim of the study was to evaluate the risk of spontaneous termination of the pregnancy, worked out from its demographic aspect. Several ideas are worthy of consideration. The risk of spontaneous intra-uterine death is cumulative, sharply increased by a repetition of such cessation of pregnancy. The same patients often undergo intentional abortion repeatedly. The respective risks of spontaneous and provoked interruption of pregnancy have been studied in greater detail as a function of parity.


The suppressive effect of the interferon on the ability of mouse spleen cells synthesizing IgE to sensitize rat skin for heterologous adoptive cutaneous anaphylaxis. Mouse spleen cells which are synthesizing IgE can sensitize rat skin for HACA. When such cells are treated with mouse interferon, their ability to sensitize rat skin is reduced or completely inhibited. Two hundred PRD50 units of interferon reduced HACA reactions by more than 50%; 600 units gave complete inhibition. Interferon may act by inhibiting IgE synthesis and/or release.


[Ligation of the internal iliac arteries in cases of placenta accreta]. Three cases of excessive hemorrhage in the third stage due to Placenta accreta are described. The authors preferred to treat these cases by ligation with catgut of the internal iliac arteries instead of hysterectomy, because the patients were young and likely to want more children. The results were very satisfactory: The hemorrhage was controlled in each case. By mean of arteriography, hysterography, and endometrial biopsy they were able to show that the I.I. arteries became patent after 3-4 months, and all the uterine functions were completely restored. Two pregnancies with normal delivery, occurred out of these 3 cases.


Effects of C-reactive protein on platelet function. II. Inhibition by CRP of platelet reactivities stimulated by poly-L-lysine, ADP, epinephrine, and collagen. It was recently demonstrated that C-reactive protein (CRP)4 inhibits the response of human platelets to heataggregated human gamma-globulin and thrombin and that this inhibition is characterized by a dose-dependent reduction in aggregation, activation of platelet factor 3 (PF3), and release of beta-glucuronidase. In the present experiments, CRP was found also to inhibit the ability of washed human platelets to aggregate in response to poly-L-lysine (PLL); in these experiments, the magnitude of the inhibitory effect was dependent upon the m.w. of PLL used as the stimulating agent, and was more effective with low (15,000 daltons) than with high (400,000 daltons) m.w. polymers. CRP similarly inhibited ADP- and epinephrine-stimulated platelet aggregation in platelet-rich plasma (PRP), and this was characterized by relatively minimal suppression of the primary wave  of aggregation. CRP also inhibited the platelet aggregation induced by collagen in PRP, although it had no effect upon the adherence of platelets to collagen. Finally, CRP inhibited the activation of PF3  and the release of serotonin during stimulation of platelets with ADP, and this inhibition was temporally related to the onset of the secondary wave of aggregation. These experiments extend the platelet reactivities inhibited by CRP,  show that CRP expresses its inhibitory capacity in platelet-rich plasma as well as upon isolated platelets, raise the possibility that CRP exercises its effects by inhibiting or interfering with the release and/or utilization of endogenous platelet ADP, and support the concept that CRP plays an important role in the control of platelet responsiveness to a variety of stimuli during acute inflammatory reactions.


Metabolic studies of guinea pig basophilic leukocytes in short-term tissue culture. I. Measurement of histaminesynthesizing capacity by using an isotopic-thin layer chromatographic assay. Mature circulating guinea pig basophils, purified to comprise 25% or more of leukocytes, have been successfully maintained in short-term tissue culture for up to 72 hr. These cells were found to retain the ability to synthesize histamine, as assayed by a new isotopic-thin layer chromatographic assay which can reliably detect as little as 0.5 pg of 3H-histamine. Cell-associated, newly synthesized histamine was detectable as early as 1 hr of culture, was substantially increased at 6 hr, and reached maximal levels at 24 hr, when it accounted for approximately 6.5% of total cell histamine. Newly synthesized histamine was still detectable at 48 and 72 hr of culture. Histamine synthesis was decreased by lwoering the concentration of histidine in the culture medium, and was markedly reduced by all the specific histidine dedarboxylase (HDC)3 inhibitors tested, but not by alpha-methyl-DOPA, pyrilamine maleate, or metiamide. Increasing the concentration of pyridoxal phosphate, the HDC coenzyme, above that normally present in culture medium resulted in only an equivocal increase in the amount of newly synthesized histamine, whereas aminoguanidine, an inhibitor of histaminase, had no detectable effect. Uptake of exogenous histamine by cultured basophils was trivial compared to histamine synthesis. Both newly synthesized and previously manufactured, nonisotopic, histamine seemed to be stored in the same pool, as the same proportion of both was released by concanavalin A (Con A). Cellular histamine was largely conserved, with little or no spontaneous release into the medium of detectable isotopic or nonisotopic histamine. These techniques provide a model for studying granulocyte metabolic processes in vitro, and should assist in the direct investigation of a variety of their physiologic functions.


Immunologic cross-reactions between the specifically localizing cells (SLC) generated in response to sheep RBC and the red cells of other species. Some of the lymphoid cells selectively incorporating radioactive thymidine 3 days after primary immunization with SRBC which are capable of specifically localizing in the lymph nodes of adoptively immunized syngeneic recipients challenged with SRBC (SLC-SRBC)2 are also capable of specifically localizing in lymph nodes challenged with the red blood cells of a varieth of other mammalian species. The one nonmammalian RBC tested, CRBC, failed to cross-react with SRBC by this parameter even qualitatively, although it remains possible that a feeble cross-reaction might be demonstrated with large enough experimental groups. As expected, the magnitude of the observed cross-reactions seems to vary inversely with the phylogenetic distance between the species, with ORBC showing the strongest cross-reaction (41 to 49%), ARBC showing the weakest (8 to 13%), and BRBC and HRBC occupying intermediate positions (13 to 20%). Cross-reaction between secondary anti-SRBC antibodies and the red cells of the other species were weak and inconstant, suggesting that the observed cross-reactions of specific localization may involve T cells more than B cells. During the course of these studies, it was also possible to verify experimentally our impression that with existing methods of selectively labeling SLC it is possible to study the phenomenon of specific localization using only one population of labeled cells, providing certain essential controls are employed.


Leukocyte-derived complement inhibitor. IV. The functional properties of C1 bound to erythrocytes pretreated with leukocyte culture supernatant. E, pretreated with leukocyte cultures supernatant (ES), binds C1 through C1q; ES and EIgM that bind the same amount of C1 as measured in a hemolytic assay have the same uptake of 125I-C1q; ESC1q and EIgMC1q, carrying the same number of molecules of CUq per cell, have the same uptake of CUr and CUs; soluble immune compleses prevent the binding of C1 and C1q to ES. The activity of C1 bound to ES is impaired; ESC1 can react with C4 but not with C2. The C4 turnover and the C1 ING turnover by ESC1 are reduced so that ES-bound C1 is protected from destruction by C1 ING. These modifications are fully reversed when C1 is transferred from ES to EA:C1 recovers its ability to react with C2, and C1 INH. Thus the C1s activity can be modulated inside the C1 molecular complex upon binding of C1q to a lymphocyte product. In addition, the 125I-C1q uptake is proportional to the amount of IgM hemolysin used to sensitize E; it has, however, an exponential relationship to the amount of IgG or S used to sensitize E. The ratio of 125I-C1q uptake towhole C1 uptake measured in a hemolytic assay is lowerthan 2. This indicates that one molecule of IgM is sufficient to bind one molecule of C1q on E, that several molecules of IgG or S are required to bind one molecule of C1q, and that one molecule of C1q is sufficient to create a lytic site on E.


The metabolism of IgE. Studies in normal individuals and in a patient with IgE myeloma. IgE metabolic turnover studies with purified radioiodinated IgE were performed in normal individuals and in a patient with IgE myeloma. The validity of the turnover studies was established in several ways, including comparisons of radioiodinated IgE turnover with the turnover of endogenously labeled 14C-IgE and with the turnover of infused unlabeled IgE in a patient with hypogammaglobulinemia. The geometric mean serum IgE concentration in 73 normal adults was 96 ng/ml with a 68% confidence interval of 24 to 386 ng/ml. Metabolic turnover studies in 10 control individuals disclosed a geometric mean total circulating IgE of 4.1 mug/kg, a mean percentage of the total exchangeable IgE in the intravascular space of 41%, a mean half-time of survival of IgE of 2.7 days, a mean fractional catabolic rate of 94% of intravascular pool per day, and a geometric mean synthetic rate of 3.8 mug/kg/day. IgE has the lowest synthetic rate and highest fractional catabolic rate of the five major classes of immunoglobulin molecules. In contrast to these normal values, a patient with IgE myeloma had a serum IgE comcentration of 42 mg/ml, a total circulating IgE of 1.7 g/kg, and a synthetic rate of 270 mg/kg/day. Furthermore, although the synthetic rate was vastly increased, the survival time was prolonged and the fractional catabolic rate was decreased to 5.1 days and 16 to 22% of the intravascular pool per day, respectively. These data are compatible with the concept that IgE is catabolized in part by a mechanism common to all immunoglobulin classes and in part by a unique mechanism not available to other immunoglobulins. At very high IgE serum concentrations, such as those encountered in patients with IgE myeloma, the unique mechanism would be saturated and only the catabolic pathways available to all immunoglobulins would be available to IgE.


Inhibition of normal allogenic lymphocyte mitogenesis by a soluble inhibitor extracted from human colonic carcinoma. Soluble extracts from human colonic tumors (STE) and from their hepatic metastases (SHME) were found to be unable to induce a proliferative response among normal allogenic lymphocytes. However, addition of these tissue extracts to cultures stimulated with various mitogens resulted in an almost complete inhibition of lymphocyte DNA synthesis. Nevertheless, they did not reduce the unstimulated lymphocyte spontaneous proliferation. Control experiments have shown that normal or nonmalignant tissues do not affect the lymphocyte  reactivity to mitogens. The specific immunosuppressive evvect was found to be irreversible and to block lymphocyte activation at an early stage. The inhibitor was soluble (not sedimented at 220,000 times G for 2 hr) and not nonspecifically cytotoxic. STE was slso found to induce morphologic alterations resulting in blastlike cell production. However, no mitotic figures were seen, even after colchicin treatment. It is suggested that STE might contain molecular component(s) which would exert a double effect: 1) trigger metabolic alterations responsible for the blast-like cell induction, and 2) inhibit the lymphoproliferative response. The significance of such a mechanism is discussed in conection with the nonspecific immunosuppression caused by a tumor and the immune unresponsiveness against the tumor itself. A preliminiary characterization of this tumor material has shown that its molecular weight was about 70,000 and that it is not related to carcinoembryonic antigen or alpha-fetoprotein.


Early and late contact sensitivity reactions in guinea pigs senstitzed to oxazolone. Inbred strain 2 and random-bred guinea pigs injected oxazolone in incomplete or complete Freund's adjuvant showed contact reactions within an hour after topical application when tested 3 weeks post-sensititization. The application when tested 3 weeks post-sensitization. The time for appearance of skin reactions at 5 days post-sensitization was 8 to 24 hr, more along classic delayed-type hypersensitivity lines. Immune serum harvested several weeks after sensititazation was effective for passive transfer of early skin reactivity, while serum at 5 to 10 days was not. Lymph node cells taken 5 days after sensitization of donors could transfer only the late skin reactivity to histocompatible recipients; lymph nodes taken at 15 days did not contain cells capable of such transfers. The heterogeneity of mechanisms involved in the production of contact dermatitis suggested by these results provides new approaches to studies in this area of allergy research.


Xenogenization of rat erythroid cells by lymphatic leukemia virus: its role in induction of autoimmune hemolytic anemia. Newborn rats given injections of low doses of Friend lymphatic leukemia virus subsequently developed hemolytic anemia characterized by production of antierythrocyte autoantibody. Electron microscopy showed C-type virus particles budding from the cell membrane not only of lymphoid cells but also of erythrocyte percursor cells in bone marrow and spleen, suggesting that the erythroid cells were infected by the virus. In addition, erythrocyte precursor cells expressed virus-induced cell surface antigens detected by cytotoxicity tests. Normal syngeneic rats preimmunized with a Friend lymphatic leukemia virusinduced tumor and subsequently inoculated with bone marrow, spleen cells, or reticulocyte-rich fraction derived from other rats injected with high doses of the virus at birth produced cytotoxic antibody to the virus-induced tumor and antierythrocyte autoantibody. In contrast, rats subsequently inoculated with virus-infected thymus or lymph node cells produced cytotoxic antibody but not antierythrocyte autoantibody. These results indicate that "xenogenization," previously shown for tumor cells and normal lymphoid cells, is also observed for rat erythroid cells and, further, that xenogenization of erythroid cells by Friend lymphatic leukemia virus is one of the most important factors in induction of autoimmune hemolytic anemia.


Activation of the alternative complement pathway by water-insoluble glucans of streptococcus mutans: the relation between their chemical structures and activating potencies. Water insoluble, sticky glucan was synthesized by reacting glucosyltransferase obtained from the sulture filtrate of cariogenic Streptococcus mutans OMZ 176 on sucrose. This glucan (OMZ 176 glucan), that consisted of the backbone chains of consecutive alpha-1, 3 glucosidic linkages (65%) and the side chain of alpha-1, 6 glucosidic bonds (35%), showed an ability to activate the alternative pathway of the complment system in human serum. Water soluble glucans synthesized from the reaction of glycosyltransferases of S. mutans strain AHT, FA-I, and Ingbritt with sucrose, that have a high content of alpha-1,6 and a low content of alpha-1, 3 glucosidic linkages, were less effective to activate the complement system. Sephadex (G-25) and Dextran (T-2,000 and T-40), that consisted exclusively of alpha-1, 6 glucosidic linkages, did not significantly activate the complement system. Controlled Smith degradation products of OMZ 176 glucan, composed of the alpha-1, 3 linked glucose backbone chain alone, lost its activity. From these results it was concluded that both backbone chain of alpha-1, 3 glucose units and branched alpha-1, 6 glucose units were essential for the OMZ 176 glucan to activate the alternative pathway of the human complement system.


Mechanism of the growth-promoting effect of serum albumin on concanavalin A-activated lymphocytes: protective effect of the plasma proteins. The concentration of concanavalin A (Con A) required for optimal growth of lymphocytes is 10 to 20 times greater in the presence of plasma than in the presence of serum albumin (BSA). This shift in Con A requirement is mainly caused by Cohn fractions III and IV, which bind and probably remove free Con A. Aymphocytes, once they are activated by Con A, lose all proliferative activity unless protected by certain proteins. Cohn fraction VI and beta-lactoglobulin were found to be most effective in protecting the cells. The protective proteins do not promote growth; only BSA promotes growth of Con A-activated lymphocytes. The mechanism of the growth-promoting effect of BSA on Con A-activated lymphocytes was investigated. The continous presence of BSA in the culture medium durdly reduces, whereas protein-free medium abolishes, growth. The mechanism of the growth-promoting effect of BSA is not concerned with regulating the uptake of Con Aby lymphocytes. Red blood cells, crenated by washing in protein-free medium, revert immediately to their normal globular shape by the addition ofBSA or FAFBSA, whereas the protective proteins fail to do so, indicating a direct effect of BSA on the external surface of the erythrocyte membrane and presumably also of the lymphocyte. The hypothesis is proposed that BSA promotes growth by conveting total structural integrity to the cell surface membrane of Con A-treated lymphocytes.


Chemotactic and bactericidal capacities of human newborn monocytes. We evaluated the chemotactic and bactericidal capacities of human cord blood monocytes, and the ability of cord lymphocytes and sera to generate chemotactic (LDCF) and opsonic factors for monocytes. Our results suggest that the intrinsic locomotive capacity, and the receptor system for LDCF, are adequately developed in the newborn monocyte. Moreover, newborn lymphocytes appear to produce adequate amounts of LDCF, capable of attracting adult monocytes. Poor chemotaxis was observed only when cord monocytes were exposed to supernatants of cord lymphocytes, which suggests that both contribute to this abnormal response. An inhibitory factor for which only cord monosensitivity of monocytes and strength of chemotactic factor between adults and newborns would explain these results. Bactericidal capactiy of cord monocytes against Escherichia coli K-12 opsonized by either cord or adult serum was comparable to that  of adult monocytes.


Solubilization of IgA immune precipitates by complement. The complement (C) system can solubilize immune precipitates prepared with antibodies of the IgG class, and apparently also of the IgM class. This paper shows that C can also solubilize immune precipitates prepared with two different antigen-binding IgA myeloma proteins. Immune precipitates were prepared with a) mouse myeloma protein TEPC 15 and PC-KLH, and b) mouse myeloma protein MOPC 315 and DNP-BSA. The precipitates could be solubilized by fresh mouse serum, but not by zymosan- or heat-inactivated serum. The rate of solubilization was not affected by the removal of of Ca++ ions. These results verify that the C-mediated solubilization effect can proceed entirely via the alternative C pathway, and lend increased support to the view that the effect is a general phenomenon, not restricted to a particular antibody class or type of antigen.


Generation of a neutrophil chemotactic agent by spermatozoa: role of complement and regulation by seminal plasma factors. The interactions of polymorphonuclear leukocytes, spermatozoa, seminal plasma, and serum have been examined in an in vitro leukocyte chemotaxis system. Bovine or human spermatozoa have no neutrophil chemotactic activity alone, but generate potent activity when incubated with serum. Generation of this activity requires magnesium, but not calcium ions and is blocked by pre-heating the serum. Chemotactic activity is generated normally in serum deficient in immunoglobulins or C4, but is not produced in serum deficient in C3. Thus, spermatozoa activate complement via the alternative pathway. The chemotactically active agent has been identified as the low m.w. C5 cleavage product (C5a) on the basis of heat stability, gel filtration characteristics, and specific inhibition by anti-serum to C5. The spermatozoal constituents responsible for complement activation are largely heat stable, resistant to diisopropyfluorophosphate and on gel filtration compise a heterogeneous group of large m.w. materials. Bovine seminal plasma has no neutrophil chemotactic activity alone; considerable activity, however, is generated by incubating low, but not high concentrations of seminal plasma with serum. The chemotactic agent produced in serum is C5a. Bovine seminal plasma also contains potent heat labile inhibitors of chemotaxis. Two distinct inhibitors differing in m.w. (50 to 100,000 and 15,000) and heat stability have been isolated. The inhibitors appear to act directly on the neutrophil rather than on the chemotactic factor. Human seminal plasma exhibits slight chemotactic activity alone but does not generate significant additional activity on incubation with serum. In contrast to the inhibitory activity of bovine seminal plasma, the human material contains heat-stable, nondialyzable factors which enhance the neutrophil chemotactic response. These studies document a specific mechanism for the directed migration of polymorphonuclear leukocytes toward spermatozoa. The findings may provide an explanation for  the observed in vivo leukocyte accumulation in the female genital tract in association with spermatozoa and seminal plasma. The biologic significance of this phenomenon relates to potential leukocyte-spermatozoa interaction which may influence the likelihood of fertilization.


Large-scale isolation of Dane particles from plasma containing hepatitis B antigen and deomnstration of circular double-stranded DNA molecule extruding directly from their cores. A method was developed to isolate, on a large scale, Dane particles from five liters of pooled plasma of asymptomatic carriers of hepatitis B antigen. It involved three successive ultracentrifugation procedures; the final preparation was more than 98% pure in Dane particles. Purified Dane particles had the density of 1.23 to 1.24 g/cm3. The concentration of nucleic acids in the preparation containing purified Dane particles was too low to be detected either by chemical or by spectrophotometric method. However, a circular double-stranded DNA molecule extruding directly from the core of Dane particles was clearly demonstrated by elelctron microscopic observations. The cores of Dane particles (hepatitis B core antigen; HBCAg) were prepared by treating the Dane particle preparation with mercaptoethanol and Nonidet P-40. They were sufficient both in purity and amounts to allow the determination of antibody to HBCAg by an immune adherence hamagglutination method.


Specific antisera produced by immunization with precipitin lines. Individual plasma proteins were precipitated, identified and isolated on the basis of line immunoelectrophoresis. A monospecific antibody response was induced by immunization of rabbits with less than 50 ng of precipitated antigen. Preservation of monospecificity was obtained by reimmunization with precipitates developed against the specific antisera.


Enrichment of PHA transformed lymphocytes in samples containing mixed populations. A dextran density gradient centrifugation method has been used to separate PHA transformed lymphocytes from nontransformed lymphocytes obtained from rat blood. Fifty-four percent of the transformed lymphocytes were recovered in the fraction at a density of 1.0620 g/ml. Eighty-five percent of the cells in this fraction were transformed cells while the remainder were non-transformed lymphocytes.


The fibrous proteins of stratum corneum. The proteins of cow snout stratum corneum can be extracted in part with Tris buffer, pH 9.0, containing 6 M urea. Sodium dodecyl sulfate (SDS)-polyacrylamide gel electrophoresis shows that about half the extracted material migrates as prekeratin when the extract is treated with both SDS and mercaptoethanol; only trace amounts of the proteins migrating as prekeratin are seen when SDS alone is used. The urea extract gives precipitin lines to an antibody against prekeratin. After exhaustive extraction with the Tris-urea buffer an additional amount of protein is solubilized by extraction with buffer containing mercaptoethanol. This extract shows an electrophoretic pattern similar but not identical to prekeratin. These results suggest that the stratum corneum contains fibrous proteins with different degrees of cross-linking. An analogous system has also been observed in human stratum corneum.


Patterns of glucose catabolism during differentiation of fetal rat epidermis. Glucose metabolism has been investigated during differentiation of fetal rat skin to evaluate shifting patterns in the catabolism of this major exogenous substrate in relation to changing requirements during epidermal maturation. Glucose utilization and aerobic glycolysis declined while oxidative metabolism increased in whole skin as stratification and cornification progressed. Activity of the hexose monophosphate shunt was quantitated in isolated epidermis for the first time. The relative activity of this pathway diminished somewhat from 20% to 12% of utilized glucose as the granular layer and stratum corneum developed. The results are consistent with (a) enhanced utilization of glucose, aerobic glycolysis, and hexose monophosphate activity in rapidly proliferating eidermis, and (b) flexibility of glucose catabolism in response to cellular requirements at different stages of differentiation.


Arginine transferase activity in homogenates from guinea-pig hair follicles. The transfer of arginine from tRNA to the amino terminal region of acceptor proteins has been demonstrated in postribosomal supernatant from guinea-pig hair follicle homogenate. The reaction has no requirement for template nucleic acids, ATP, GTP, or Mg++, and is unaffected by high concentrations of cycloheximide. It is concluded that the arginine transfer activity of the guinea-pig hair follicle is due to the action of a soluble enzyme similar to the arginine transferases previously described for other mammalian tissues.


Spark source mass spectrographic study of metal allergenic substances on the skin. By spark source mass spectrography it is possible to trace very low concentrations of substances such as chromium, cobalt, and nickel in ethanol extracts of the skin. Chromium could be detected in abnormally high concentrations 3 weeks after one application, while nickel and cobalt reached background levels after 2 to 3 weeks. Touching a door handle containing chromium leads to a significant rise in the chromium content of the skin. Increased chromium content of the skin was evident in one case of wristwatch eczema as well.


The induction of photocontact sensitivity in guinea pigs without UVB radiation. Allergic photocontact sensitization could be induced in guinea pigs with 3,3',4',5-tetrachlorosalicylanilide (TCSA), 3,4',5-tribromosalicylanilide (TBS), and bithionol using pretreatment with sodium lauryl sulfate (SLS) and long-wave ultraviolet (UVA) radiation. Mid-wave ultraviolet below 320 nm (UVB) was not necessary for the induction of sensitization. Combined use of SLS pretreatment with UVA radiation resulted in more effective sensitization than combined UVB and UVA radiation. Higher sensitization rates to TCSA and TBS were achieved by allowing rest periods between each of 5 2-hr exposures to UVA than by daily 1-hr exposures for 10 consecutive days. The opposite result was obtained with bithionol. Although UVB has been customarily used in the past for induction of photosensitivity, its role is only to irritate the site of induction.


Lymphocyte-epithelial cell interactions in oral mucosal inflammatory diseases. Lymphocyte cytotoxicity for target cells is a method for evaluating specific lymphocyte stimulation. In vitro lymphocytotoxicity has been demonstrated in chronic ulcerative colitis and granulomatous colitis, polymyositis and dermatomyositis, systemic scleroderma, recurrent aphthous stomatitis, and periodontal disease. We have investigated lymphocytotoxicity in 36 patients with various oral inflammatory diseases using an automated cell-counting system. This investigation demonstrated in vitro lymphocytotoxicity for gingival epithelial target cells by aggressor lymphocytes harvested from patients with recurrent aphthous stomatitis and periodontal disease. This effect was not seen when the lymphocytes were harvested from normal subjects or from patients with other oral mucosal inflammatory diseases. The automated cell-counting system corresponded very well with the assay technique of exclusion of supravital dye.


Cutaneous effects of pulsed nitrogen gas laser irradiation. The effects of pulsed nitrogen gas laser emission (337.1 nm wavelength) were studied on human skin. The laser provides high-intensity monochromatic UVA radiation and can elicit delayed erythema in an actual exposure time of about 1 msec (105,000 pulses, each lasting 10 nsec, delivered over 210 sec). The effects of nitrogen laser irradiation were compared clinically and histologically with conventional erythemogenic UVA and UVB exposures from xenon arc or mercury arc lamps and were found to be similar in many respects. The minimal erythema dose is comparable to that obtained using more conventional continuous light sources which have more than 100 times lower intensity. A phototoxicity comparison of oral and topically applied psoralens is presented, indicating that the laser may prove useful in comparing photosenitizing capacity of certain compounds.


Role of maternal antibody in pneumonia and bronchiolitis due to respiratory syncytial virus. Fifteen infants with pneumonia caused by respiratory syncytial virus (RSV) and 19 infants with bronchiolitis caused by RSV were studied for the influence of homologous, circulating neutralizing antibody on the severity of their illness. All infants were under nine months of age. Although maternal neutralizing antibody did not prevent infection with RSV and illness, the severity of pneumonia caused by RSV was inversely related to the level of neutralizing antibody. The severity of bronchiolitis caused by RSV was unrelated to maternal antibody levels. Chest roentgenograms showed pneumonia to be slightly more severe than bronchiolitis. Neither the severity of illness nor the presence of maternal neutralizing antibody was related to the development of complement-fixing antibody.


Radioimmunoassay for antibody to hepatitis B surface antigen shows transmission of hepatitis B virus among household contacts. The epidemiology of infections with hepatitis B virus was studied by measurement of serum antibodies to hepatitis B surface antigen (HBS Ag) with the radioimmuno-precipitation test. Prospective studies of household contacts of HBS Ag-positive patients with acute hepatitis demonstrated that four of 41 children and one of 60 adults experienced anicteric seroconversions. Two of the 60 adults also had mild icteric hepatitis and became chronically antigenemic. Neither HBS Ag nor antibody to HBS Ag was detected in follow-up blood samples from 85 seronegative contacts of HBS Ag-negative patients with hepatitis, although seven icteric secondary cases were identified. Household contacts of HBS Ag carriers frequently had serologic evidence of exposure to hepatitis B virus (44% of adults), but the remainder had neither detectable antigen nor antibody.


Morphology, ultrastructure, and mode of division of Mycoplasma fermentans, Mycoplasma hominis, Mycoplasma orale, and Mycoplasma salivarium. The morphology of viable Mycoplasma fermentans, Mycoplasma hominis, Mycoplasma orale types 1 and 2, and Mycoplasma salivarium was studied in broth cultures by interference microscopy and in thin sections by electron microscopy. Only spherical cells were seen by interference microscopy. M. hominis had a capsule-like outer layer. Except for M. orale type 1, mycoplasmas in thin sections were 0.3-1 mum in diameter, with a bounding trilaminar membrane 7.5-10 nm thick. The mycoplasmas contained DNA fibrils and randomly distributed ribosomes. No polyribosomes were seen. Dividing mycoplasmas elongated slightly; the membrane invaginated, forming one bud. Sometimes M. hominis and M. salivarium produced one bud by elongation, and the bud was attached by a tube. This method of division is not considered as characteristic but rather as due to centrifugal force separating unfixed cells during preparation for electron microscopy. Cross-septa were never observed. In thin sections M. orale type 1 was elongated and without buds, an observation which suggested that preparation for electron microscopy distorted the mycoplasmas.


Antigen dose response and specificity of production of the lymphokine eosinophil stimulation promoter. The present investigations of the recently discovered lymphokine eosinophil stimulation promoter have (1) shown that the assay system is highly sensitive and reproducible via the establishment of dose-response curves and their statistical analysis, (2) demonstrated that the direct assay is specific with use of eosinophilrich peritoneal exudate cells obtained from mice with either schistosomiasis or trichinosis, (3) demonstrated that the indirect test with splenic lymphocytes is specific with use of both the above method and radioisotope-labeled antigens, and (4) provided information on the roles of eosinophils and mononuclear cells via purification, reconstitution, and the use of antiserum to eosinophils.


The nature of aleutian disease in mink. I. Two forms of hypergammaglobulinemia as related to method of disease transmission and type of lesion. Aleutian mink disease is generally considered to precipitate spontaneously in ranch mink, with a lethal outcome. A two-year field study of a herd of susceptible mutant mink (sapphires and violets), however, has shown that all individual mink were affected from birth; the well state consisted of periodic low-level hypergammaglobulinemia accompanied by minute vascular occlusions. The spontaneous lethal change in an individual appeared to arise during one of these hypergammaglobulinemic episodes and thus represented a failure of the immune system to control an inherent virus-induced mononucleosis. The fact that the entire herd was affected by the periodic form from birth is considered strong evidence for vertical transmission at a rate of 100%. The incidence of spontaneous precipitation was found to be dependent on the level of hypergammaglobulinemia in the mother during pregnancy.


Synergism between amikacin and cefazolin against Klebsiella: in vitro studies and effect on the bactericidal activity of serum. Synergism between amikacin and cefazolin was studied in vitro in 20 strains of Klebsiella isolated from clinical material. Several techniques for the demonstration of synergism in vitro were employed. The checkerboard technique with use of bactericidal end points and the killing curves method showed synergism between amikacin and cefazolin for 13 and 15 strains, respectively. The two techniques were in accordance in 12 instances. The data obtained in vitro were correlated with the bactericidal activity in sera from 10 subjects who had received the usual doses of amikacin and cefazolin, alone or in combination. The sera of subjects who received amikacin plus cefazolin were bactericidal at significantly higher dilutions than sera of patients who received cefazolin alone. The increased serum bactericidal activity in subjects receiving amikacin plus cefazolin was observed only for strains against which these antibiotics were synergistic in vitro.


beta-Lactamase activity in Chromobacterium violaceum. A strain of Chromobacterium violaceum isolated from a fatally infected patient was found to produce a beta-lactamase. When the organism was grown in drug-free medium, beta-lactamase activity was barely detectable, but when it was grown in the presence of penicillin G, a much larger amount of activity was produced. The beta lactamase was active primarily against cephalosporins; it was sensitive to inhibition by cloxacillin but resistant to p-chloromercuribenzoate. Thus this enzyme closely resembled the common type of beta-lactamase found in Pseudomonas aeruginosa. The organism was relatively susceptible to ticarcillin, carbenicillin, and cefoxitin, which resected hydrolysis by its beta-lactamase, but was quite resistant to 11 other beta-lactam antibiotics. Production of the beta-lactamase appeared to be mediated by chromosomal genes.


Distribution and characteristics of hepatitis B surface antigen in body fluids of institutionalized children and adults. Specimens of blood, feces, urine, and nasopharyngeal washings collected at regular intervals from subjects in an institutionalized population were tested for the presence of hepatitis B surface (HBS Ag) and antibody by passive hemagglutination, radioimmunoassay, and immune electron microscopy. HBS Ag, confirmed by radioimmunoassay and immune electron microscopy, was frequently detected in nasal washings, urine, and feces of chronic carriers of HBS Ag and occasionally in subjects with recent seroconversion for HBS Ag. In addition, some subjects who had recently become positive for antibody to HBS Ag in serum had HBS Ag transiently present in urine and occasionally in the feces, without demonstrable antigenemia.


Longitudinal studies of types A and B influenza among Seattle schoolchildren and families, 1968-74. Longitudinal studies of influenza were conducted by postepidemic collection of sera and illness information among Seattle schoolchildren from 1968 to 1974 and in family groups from 1972 to 1974. The rate of infection with A/Hong Kong (H3N2) virus was lowest in the 1968-1969 epidemic; rates were twice as high in the epidemics of 1970 and 1972, and in the A/England (H3N2) epidemic of 1973. The introduction of a new strain of influenza type A or type B caused higher rates of infection in junior high than elementary schoolchildren. For influenza A, a shift in strain was associated with higher rates in the urban area than in the suburban area. The proportion of adolescents with serological evidence of infection who reported typical illness was 40%-42% in all three A/Hong Kong epidemics and 54% during the A/England epidemic. Reinfection with the A/Hong Kong strain was rare. Recent natural infection with the A/Hong Kong virus (1972) afforded 62% protection in the 1973 epidemic of A/England influenza.


Monocyte function in infectious mononucleosis: evidence for a reversible cellular defect. Migration of blood monocytes from patients with acute infectious mononucleosis and from normal controls was measured against chemotactic factors in serum. Moncytes from patients with acute infectious mononucleosis showed decreased migration as compared with that of control monocytes. However, serum from patients with infectious mononucleosis contained normal or above normal amounts of chemotaxins for monocytes. The migratory defect of monocytes from patients with infectious mononucleosis was reversible within three months after the onset of diesease. The cause of this monocyte migration defect in infectious mononucleosis is though to be an in vivo blockade of receptors on monocytes for chemotaxins, and it is speculated that this defect can partially explain the explain the ablated delayed-hypersensitivity skin reactions in this disease.


Effect of serum and nasal neutralizing antibodies on bovine respiratory syncytial virus infection in calves. Calves exposed to a bovine respiratory syncytial virus showed mild clinical signs of respiratory illness and responded serologically. The disease occurred in the presence or absence of circulating antibodies, but there was no evidence of exacerbation of the disease due to preexisting serum antibody. Nasal secretory antibody appeared to protect the calves against the disease. Calves previously exposed to the virus were immune to challenge. The virus was recovered at a high frequency when specimens of nasal secretion (not subjected to freezing and thawing) were inoculated into susceptible cells within 1 hr after collection.


Effect of alveolar lining material on phagocytic and bactericidal activity of lung macrophages against Staphylococcus aureau. Unstimulated rabbits were sacrificed and their lungs washed with heparinized saline. After alveolar macrophages were harvested, the cell-free lavage fluid was centrifuged at 47,000 X g to recover a small, whitish, surface-active pellet (F fraction.) The supernatant was concentrated 15-fold by vacuum dialysis (P fraction). Alveolar macrophages in a serum-free system were challenged with radiolabeled (32P) Staphylococcus aureus preincubated in either balanced salt solution or F or P fraction. A small increase in alveolar macrophage bacterial uptake occurred with P fraction-treated staphylococci. P fraction from locally immunized animals further enhanced phagocytosis. In bactericidial experiments, alveolar macrophages were allowed to phagocytize staphylococci preincubated in either balanced salt solution or F fraction. Intracellular bactericidal activity of alveolar macrophages was quantitated by lysotaphin lysis of extracellular bacteria and quantitation of viable intracellular bacteria. Enhanced lung macrophage bactericidal activity against F fraction-incubated staphylococci was noted.


Mechanism of the increased splenic erythropoiesis in mice treated with estradiol benzoate. Pharmacological doses of estrogens induce osteosclerosis of the bone marrow, and depress colony-forming units (CFU's) and platelet and leukocyte counts in mice. A compensatoryincreasts in mice. A compensatory increase in splenic erythropoiesis prevents a fall in the hematocrit. The mechanism of this compensation was investigated as follows, BDF1 female mice were injected subcutaneously thrice weekly for 6 weeks wiht 50 mugg of estradiol benzoate (EB) or sesame oil (SO). Subsequently the hematocrit, red cell mass (RCM), and 4 hour per cent of 59Fe uptake into the femurs and spleens were determined in groups of five mice for 4 consecutive days. The RCM and hematocrit were not significantly different in the two groups. The per cent of 59Fe uptake into the femurs of EB-treated mice was less than 30 per cent of that in SO-treated mice and the per cent of 59Fe uptake into the spleens of EB mice was more than two times that in SO mice. To ascertain whether the increase in plenic erythropoiesis resulted from an increase in the number of splenic erythropoietin-responsive cells (ERC), the 4 hours per cent 59Fe uptake into the spleen was determined in continuously hypertransfused EB and SO mice injected with erythropoietin (Ep). Whereas hypertransfuction depressed the splenic per cent of 59Fe uptake in EB and SO mice equally, injection of Ep increased the per cent of 59Fe uptake into the spleens of of EB mice to greater than two times that of SO mice. Next, the plasma Ep level of mice injected with EB or SO for 2, 4, or 6 weeks was determined after exposure of the animals to hypoxia. Ep titers were greater than three times higher in EB mice than in SO mice, We conclude that at least two mechanisms act to cause the compensatory increase in splenic erythropoiesis after marrow suppression by EB: (1) the Ep levels rise and (2) the splenic ERC population increases. The latter is probably not due to the increased plasma Ep level because it also occurs in mice whose Ep production is suppressed by plethora.


Patterns of iron storage in dietary iron overload and idiopathic hemochromatosis. Bone marrow iron stores rise in proportion to the total body iron store in dietary iron overload. The situation in the genetic disorder of idiopathic hemochromatosis is not as clear. A method for measuring the storage iron concentration chemically on samples of bone marrow obtained by trephine needle biopsy was therefore developed. Its value as a measure of tissue iron stores was established in a preliminary investigation in which specimens of liver, spleen, and bone marrow were obtained at necropsies on 66 South African Negroes among whom dietary iron overload is common. A wide range of nonheme iron concentrations was found, but in each individual there was a highly significant correlation between the concentrations in the three tissues. Nonheme iron concentrations were then determined on trephine bone marrow biopsy specimens from eight Caucasian patients with untreated idiopathic hemochromatosis, and on percutaneous liver biopsy specimens from four of them. The concentrations in the livers were in the anticipated range of 5,000 mug per gram wet weight (2 per cent dry weight). In contrast the geometric mean value for bone marrow iron concentration was 186 mug per gram wet weight, a figure that fell below the fiftieth percentile for marrow iron concentrations in the South African Negroes, whereas the geometric mean liver iron concentration was above the ninetieth percentile. These findings indicate that subjects with idiopathic hemochromatosis whose liver iron stores are grossly increased do not show a comparable rise in bone marrow iron stores.


Cholesterol dynamics in autoimmune hyperlipidemia. A 69-year-old white male with autoimmune hyperlipidemia for 19 years characterized by high serum levels (1,5000 to 3,400 mg. per deciliter) of IgA firmly bound to very-low- and low-density lipoproteins (serum total cholesterol 852 +/- 51 mg./dl., free cholesterol 340 +/- 52, triglyceride 1638 +/- 411, phospholipid 934 +/- 84) received intravenously a tracer dose of cholesterol-4-14C. Serum cholesterol specific activity was followed for 337 days and analyzed by two methods: (1) compartmental analysis which revealed the best fit of a two-compartment model with rapidly exchangeable pool 710 gm. (2,563 per cent of the mean of 15 normal subjects), slowly exchangeable pool 317 gm. (651 per cent), mean transit time 92.5 days (167 per cent), turnover rate 9.23 gm. per day (654 per cent), and excretory coefficient 0.013 (25 per cent); (2) a simulated five-compartment model involving serum free, esterified, red blood cell, and rapidly and slowly exchangeable tissue cholesterols for which pool sizes of 17, 25, 2.4, 674, and 350 gm., respectively, were calculated and a turnover rate of 9.44 gm./day agreed well with that of the two-compartment model. The extreme hyperlipoproteinemia and expanded body cholesterol pools were primarily due to the impairment of feedback control of cholesterol synthesis as a consequence of the complexing of lipoprotein and IgA.


Reversible neutrophil defect in patients with bacterial endocarditis. The bactericidal capacities of neutrophilic polymorphonuclear neukocytes (PMN) from five untreated adults with bacterial endocarditis (BE), eight untreated patients with other forms of acute bacterial infection (ABI), and fourteen drug-free uniinfected normal subjects (NS) were compared with a new technique that uses five increasing bacteria-to-neutrophil ratios ranging from 1.25 to 100 Staphylococcus aureus per neutrophil. PMN from uninfected NS or untreated patients with ABI demonstrated a similar and reproducible ability to kill increasing numbers of S. aureus in 8 per cent normal serum. In contrast, the bactericidal activities of the PMN from untreated patients with BE were significantly depressed and the defect was more apparent at high ratios. Neutrophils from some of these individuals had decreased bactericidal action only at high ratios, indicating a quantitative type of neutrophil defect. There was no morphologic deficiency in the uptake of bacteria by BE neutrophils and comparable rates of glucose [-1-14C] oxidation were found in BE and control neutrophils stimulated with various ratios of heat-killed bacteria. Therefore, the observed abnormality appeared to be that of intracellular killing rather than of ingestion. The proportions of bacteria killed by the MN of untreated patients with BE improved after antibiotic treatment and became equal to those of NS or untreated ABI patients. This rapid return to normal bactericidal function by the PMN during treatment indicates that the prior deficiency was an acquired consequence of the infectious process of BE.


Severe staphylococcal disease associated with allergic manifestations, hyperimmunoglobulinemia E, and defective neutrophil chemotaxis. Neutrophil granulocyte function was determined in three patients with systemic staphylococcal infection, clinical manifestations of generalized allergic disease, and hyperimmunoglobulinemia E. Each of the patients had urticarial skin rashes before or at the time of development of staphylococcal suppurative lymphadenitis, pneumonia, or sepsis. Neutrophil chemotaxis, random migration, phagocytosis, and bactericidal capacity were assessed to determine if an abnormality in these functions might have contributed to the development of severe staphylococcal infections. Each of the three patients with generalized urticaria was found to have a marked defect in neutrophil chemotaxis. The mean chemotactic index of the patients was 12 +/- 4, whereas that of 20 controls was 72 +/- 11. Neutrophil random migration, phagocytosis, and bactericidal capacity were normal in each patient. The serum or plasma of the patients did not inhibit chemotaxis of control neutrophils and did not contain an increased concentration of the chemotactic-factor inactivator found in normal serum. Treatment of the neutrophils of these three patients with the competitive histamine H2 receptor blocking agent, burimamide, produced a significant increase in chemotactic responsiveness. These studies suggest the possibility of pharmacologic modification of neutrophil granulocyte function.


Effects of varying sodium intake on blood pressure and renin-angiotensin system in subtotally nephrectomized rats. In rats in which the renal mass had been reduced by 70 per cent, the effects of varying sodium intake on blood pressure, serum electrolytes, renin-angiotensin system, and some other parameters that were modified simultaneously were studied. Within 4 weeks, a high sodium diet (750 mEa. per kilogram) resulted in marked hypertension, whereas a standard sodium diet (150 mEq. per kilogram) elevated the blood pressure only slightly. A low sodium diet (less than 0.2 mEq. per kilogram) prevented the rise in blood pressure. In the hypertensive group, the hematocrit values were markedly decreased, indicating the expansion of extracellular and intravascular spaces. The compensatory renal hypertrophy was accelerated by the high sodium diet and retarded during restriction. During low sodium intake, the serum concentration of sodium was diminished and that of potassium elevated. During the high sodium diet, the sodium concentration was unchanged, but the potassium concentration was decreased. Subtotal nephrectomy diminished the plasma angiotensin II concentration, and the renin content of the kidney remnant was lower than that of the kidneys from control animals. Sodium restriction stimulated the renin angiotensin system markedly, whereas high sodium intake suppressed it. After subtotal nephrectomy, elevation of blood pressure, renal hypertrophy, and suppression of the renin-angiotensin system are closely related to sodium intake.


Plasmic degradation of fibrinogen Paris I. Fibrin obtained from the plasma of a patient having abnormal fibrogen Paris I contains normal alpha, beta, and gamma polypeptide chains as well as an abnormal gamma-chain (gammaParis I) of approximately 51,000 daltons molecular weight. Plasmic digestion of Paris I fibrogen and noncrosslinked fibrin yields both normal and abnormal Fragment D molecules, the latter having a higher negative charge and molecular weight than that liberated from normal fibrinogen and noncorsslinked fibrin. After disulfide bond reduction, an abnormal polypeptide chain of approximately 40,500 +/- 2,000 daltons molecular weight was demonstrated in the Paris I digests by dodecyl sulfate (SDS) polyacrylamide gel electrophoresis. Comparison with the electrophoretic pattern for reduced digests of normal substrates indicates that it is a gamma-chain remnant in the normal Fragment D. Although the carbohydrate content in the gamma-Paris I-chain is slightly higher than that in the normal gamma-chain, as measured by periodic acid-Schiff reagent (PAS) staining intensity, it is concluded that extra carbohydrate does not account for the high molecular weight of the gamma-Paris I-chain since the 40,500 dalton chain does not stain with PAS. Plasma digestion of Paris I crosslinked fibrin yields a large amount of Fragment D in addition to Fragment D-D ("D-dimer") and E molecules, in contrast to a digest of normal crosslinked fibrin, from which only the latter two fragments are formed. This finding suggests that the defect in fibrinogen Paris I derives from an abnormality in the carboxy-terminal region of the gammaParis I-chain, so that in the presence of Factor XIII, these chains are not crosslinked and Fragment D-D molecules are not liberated upon subsequent plasmic degradation. The data provide support for the previous conclusion that a longer than normal polypeptide chain sequence at the carboxy-terminal portion of the gammaParis I-chains accounts for the increased size of these chains relative to the normal gamma-chains and for the abnormal function of the intact fibrinogen Paris I molecule.


Evaluation of a new automatic device for taking and recording blood pressures. A new instrument capable of recording systolic and diastolic blood pressure automatically and repetitively is described, and its accuracy is shown to be equal to that obtained by a carefully trained observer among 53 patients with different levels of blood pressure. The instrument (BosoMat) is also shown to be more accurate than two others available, namely, the Arteriosonde Model 1213 and the SphygmoStat Model B-300. The standard deviation among three consecutive blood pressures on the same patient as determined by the new instrument or by the nurse using traditional methods is shown to be approximately 4 mm. Hg.


Effect of hydrocortisone on total body calcium in rats. Administration of 5 mg. of hydrocortisone acetate to rats every other day for 2 weeks resulted in growth retardation and weight loss as indicated by body weights of experimental animals, which averaged 33 per cent lower than those of the controls, and a significant decrease in the length of the tibiae and femurs (p less than 0.01 for treated vs controls). However, despite the smaller size of the treated animals, the values for total body calcium (TBCa) and the calcium in the tibia and femur did not differ significantly from control values. Thus, there was more calcium per unit length of bone, resulting in an increase in the skeletal density of treated rats. This finding was confirmed by x-ray examination of these bones. The net intestinal absorption of calcium (rate of initial entry) calculated from plasma levels following an oral and intravenous dose of 47Ca and 85Sr, respectively, was not significantly different in hydrocortisone-treated rats compared to controls. This would indicate that the rate of intestinal absorption of calcium is unimpaired despite the administration of massive doses and corticosteroids. When the animals were placed on a calcium-deficient diet, both TBCa and tibia and femur calcium levels were decreased. Subsequent administration and hydrocortisone did not alter the calcium values. The results of this study are compatible with the hypothesis that hydrocortisone promotes weight loss, retards growth, but inhibits the rate of bone resorption.


The dexamethasone-modified adrenal scintiscan in hyporeninemic aldosteronism (tumor versus hyperplasia). A comparison with adrenal venography and adrenal venous aldosterone. The dexamethasone-modified adrenal scintiscan, a noninvasive procedure, is described for the preoperative distinction between primary aldosteronism (aldosterone-producing ademona) and idiopathic aldosteronism (bilateral hyperplasia) and for the preoperative localization of aldostersone-producing adenomas. This procedure has been carried out on 17 subsequently proved cases of primary aldosteronism and nine cases (four unexplored) of idiopathic aldosteronism. In the tumor cases, it indicated correctly the side of the tumor in 88 per cent. It was correct in predicting the existence of bilateral hyperplasia in all of the five cases explored. It produced the same response in four more cases believed to have bilateral hyperplasia, in which surgical exploration has not been carried out. Many of the same patients had, in addition, standard adrenal scintiscans (SS), adrenal venography, and determinations of aldosterone in adrenal venous blood. These results are compared with those of the dexamethasone scintiscan (DS). In tumor localization, the 88 per cent figure for the DS was only moderately better than that of the other three (71 per cent, SS; 80 per cent, venography; 80 per cent, adrenal venous aldosterone levels). However, in predicting bilateral hyperplasia, the DS was 100 per cent correct, as were the levels of aldosterone in adrenal venous blood. The SS and adrenal venography failed in bilateral hyperplasia and gave many false-positive results indicating tumor. The DS, a relatively simple outpatient procedure, appears to be at least as effective, both in lateralizing tumors and distinguishing between tumor and bilateral hyperplasia, as the more difficult, expensive, and sometimes hazardous invasive procedure of bilateral adrenal vein catheterization.


Measurement of conjugated and unconjugated bilirubin in bile. II. A new thin-layer chromatographic method. A new thin-layer chromatographic (TLC) method is described for measurement of conjugated (CB) and unconjugated (UCB) bilirubin in bile. Bile is streaked on a silica-gel plate and developed with chloroform. Bilirubin in the mobile UCB band and stationary CB band is quantitated by diazotization from the scraped gel with p-iodoaniline reagent. Both CB and UCB in bile yielded identical azopigment absorbance. There was no contamination of the UBC band with either CB or oxidative derivatives of bilirubin, and over 98 per cent added 14C-UBC migrated with the mobile band. Recoveries from TLC averaged 98.2 +/- 4.3 per cent of the applied pigment, duplicated agreed within 10 per cent, and the method accurately detected the enzymatic and alkaline hydrolysis of CB to UCB. Concentrations of UCB in nine samples of normal human gallbladder bile were found to be less than 1.9 mg./dl. and never exceeded 1.2 per cent of the total bilirubin.


Whole blood microculture assay of human lymphocyte function. A whole blood microculture assay is described for measuring lymphocyte reactivity to mitogenic and antigenic stimulants. This assay employs heparinized whole blood, serum-free culture medium, microtiter plates, and a Multiple Automated Sample Harvester (MASH). When this assay is compared to other leukocyte assays, its major advantages include (1) the utilization of fewer lymphocytes per microculture, thuus reducing the amount of blood required per test while increasing the number of test agents and replicate cultures which can be employed in any given experiment; (2) the conservation of mitogens, antigens, drugs, enzymes, hormones, lymphokines, and other test agents, some of which are either expensive of difficult to prepare in large quantities; (3) the elimination of lymphocyte isolation and purification procedures which may disrupt the relative proportion of T cells, B cells and antigen-processing cells; and (4) the application of an automated harvester which simplifies and expedites procedures required for processing cells for liquid scintillation counting.


Ventricular arrhythmias and cardiac hemodynamics in patients with myocardial infarction. Comparison of the acute and post-hospitalization phases. Sixty-six patients with myocardial infarction (MI) were studied during the acute hospital phase and during the six months after hospital discharge. The clinical characteristics, location of infarction, and data from right heart catheterization were studied in an attempt to determine what factors were associated with ventricular rhythm disturbance. Those patients with serious ventricular arrhythmias (SVA) in the acute phase of infarction were found to have a significantly greater degree of myocardial dysfunction as measured by pulmonary artery and pulmonary wedge pressure than patients with more normal rhythm (p less than .05). Clinical classification of patients and location of infarction were not helpful in predicting SVA during the acute infarction period. Knowledge of hemodynamic data, presence of SVA and clinical characteristics in the acute infarction period were of no value in predicting the occurrence of SVA after hospital discharge patients having had an acute diaphragmatic infarction were found to have a higher incidence of SVA after hospital discharge.


Differences between supine and sitting Frank-lead electrocardiograms. Frank-lead electrocardiograms (ECGs) were recorded from 59 adult males with suspected coronary artery disease. Three records were recorded consecutively on frequency modulated tape for each patient in (1) supine position, (2) sitting position with arms relaxed, and (3) sitting position on bicycle with arms on bicycle handles. Electrodes were applied at the level of the fifth intercostal space with patients in the sitting position. Computer measurements of electrocardiographic amplitudes were averaged over ten seconds of each record with these results: (1) QRS spatial amplitudes and R amplitudes in lead z were significantly higher and R amplitudes in lead y lower for sitting than for supine positions. (2) Except for slightly higher R and S amplitudes in lead x for sitting with arms on bicycle, no significant differences were observed between the two sitting positions. (3) These postural differences are significantly greater than those resulting from day-to-day variability of electrode locations. It is hypothesized that electrode level shifts with postural changes are responsible for the observed x- and z-lead changes. For the y-lead changes, it is hypothesized that shifting blood volumes with postural changes are the cause. It is concluded that reference electrocardiographic measurements for stress testing should be obtained from resting ECGs with the patient in the same postural position as that maintained during exercise.


Polarcardiographic criteria for myocardial infarction in Chinese men. Polarcardiograms (PCG) derived from xyz leads of the Frank electrocardiogram (ECG) were recorded in the supine position in 1264 initially healthy middle-aged Chinese men who had been under continuing medical surveillance and were re-examined seven years later. Polarcardiographic criteria for myocardial infarction (MI) were demonstrated in 97 men (7.7%), but only 15 of them showed diagnostic Q waves in the electrocardiogram (ECG). Polarcardiographic criteria for MI were independent of age, but ranged from 4.3% in 464 apparently normal men to 38% in 21 men with manifestations of ischemic heart disease. The possible association of polarcardiographic criteria and a history of smoking was limited to those with clinical evidence of heart disease. The "false positive" rate of 4.3% in clinically normal men was similar to that reported in younger Canadians and in Cretan population samples.