The use of medroxyprogesterone acetate to study progestin receptors in immature, pregnant, and adult rabbit uterus.

Medroxyprogesterone acetate (MPA)3, a potent synthetic progestin, was employed as the 3H-ligand to investigate the status of the rabbit uterine progestin receptor under various hormonal conditions. MPA dissociated slowly from the cytosol and nuclear progestin receptor obtained from ovariectomized, estrogen-primed rabbits. This slow rate of dissociation permitted a partial characterization of the receptors in pregnant and immature, unprimed rabbit uteri. High affinity progestin binding to 6--7 S and 4 S macromolecular species was detected in cytosol and nuclear extracts, respectively, from these animals. In contrast to the 3 peaks of cytosol receptor activity from estrogen-primed animals which were eluted stepwise from DEAE-cellulose columns, predominantly 2 peaks were obtained with cytosols from pregnant and immature, unprimed uteri. Further studies are required to determine to what extent progestin action is modified through interaction of these binding components with themselves and other cellular proteins.


Circannual rhythms in progesterone receptor levels and functions.

Studies in this laboratory on the nuclear binding sites (acceptors) for progesterone receptor in the developed chick oviduct have resulted in the detection of seasonal variations in the levels and functions of the receptor. Cytosol preparations obtained from the chick oviducts during the winter/spring period between January and May display reduced receptor levels as well as a loss of the capacity of the receptor to bind to nuclear "acceptor" sites in vitro. The binding of [3H]P-R to whole chromatin or purified acceptor proteins reannealed to DNA display the same rhythm. No such rhythm is detected for the binding of P-R to pure DNA. Computer analysis of the data, using least squares method to fit the data to cosine curves, shows a significant fit indicating a circannual rhythm in P-R binding to the acceptor protein-DNA complex but not to pure DNA. The nuclear binding in vivo, achieved by injecting [3H]progesterone into the wing vein and analyzing the radioactivity localized in the oviduct nuclei, also displays a similar rhythm. These results support that native nuclear acceptor sites for progesterone in the chick oviduct represent protein-DNA complexes and not pure DNA. The failure of P-R to bind the nuclear acceptor sites in vivo and in vitro during this period can be explained by the two subunit hypothesis of Schrader and O'Malley, whereby one of the two subunits is absent or inactive during this period.


In vivo metabolism and binding of 6 alpha-methylprogesterone; a progestin with anti-androgenic and synandrogenic activities.

The synthetic progestin 6 alpha-methylprogesterone (6MP) was shown to have androgenic, synandrogenic and anti-androgenic actions on mouse kidney. In vitro studies indicated that 6MP competes with testosterone for binding sites on the androgen receptor in kidney cytosol and nuclei. The in vivo distribution of 6MP and testosterone differed following subcutaneous administration: Testosterone levels were 10 and 100-fold higher than those of 6MP in plasma and nuclei from prostate-seminal vesicle. In kidney nuclei, the concentrations of these two steroids were similar. In addition, kidney nuclei bound a hydroxylated metabolite of 6MP as well as the parent compound, whereas only 6MP was found in nuclei from prostate-seminal vesicle. In vivo competition studies indicated that nonradioactive 6MP and testosterone decreased the uptake of 3H-testosterone by nuclei of kidney and prostate-seminal vesicle. By contrast, 3H-6MP uptake in kidney nuclei was potentiated by the prior administration of 6MP or testosterone. These results suggest that factors in addition to the androgen receptor may be involved in the binding and mechanism of action of 6MP on mouse kidney.


The role of ligand-binding as a determinant of the structure and activation of the estrogen receptor.

The dissociation of estradiol from the estrogen receptor occurs in two kinetic phases: a fast component having a half-time of approximately 3 min and a slower, or second, dissociating component having a half-time of approximately 95 min at 28 degrees. The fast component is produced by the dissociation of estradiol from the nonactivated 4 S receptor, a monomer. Thus, the magnitude of the fast component of the [3H] estradiol biphasic dissociation curve is proportional to the fraction of the receptor in the nonactivated state. The slow component is the estradiol dissociating from the activated 5 S receptor, a dimer. The salt-extracted estrogen receptor isolated from uterine nuclei shows a single, slow dissociating component equal to the slower component of the cytoplasmic biphasic dissociation curve. Estradiol binding shifts the receptor equilibrium from the low affinity nonactivated 4 S receptor toward the high affinity activated 5 S receptor. The kinetics of estriol dissociation from the receptor shows a larger fractional magnitude for the fast component and a faster second dissociating component than estradiol. This suggests that estriol transforms a smaller fraction of the receptor to the activated state and that the activated estriol receptor has a shorter half-time than estradiol. The biphasic dissociation kinetics of an estrogen from the receptor provides a new and sensitive criterion for measuring receptor activation.


Structural relationships between the chick oviduct progesterone receptor A and B proteins.

The chick oviduct contains two distinct forms of the progesterone receptor, termed progestophilins A (Mr = 79,000) and B (Mr = 117,000). Although these two hormone-binding proteins differ significantly in physico-chemical characteristics, a good deal of similarity exists between these two molecules. Thus, both proteins display identical hormone-binding kinetics and steroid specificity. The hormone-binding fragments obtained after the action of an endogenous oviduct Ca2+-activated protease are indistinguishable as analyzed by gel filtration chromatography. Both the A and B proteins are capable of binding to DNA-cellulose, although they elute at very different salt concentrations when subjected to gradient elution. In spite of these similarities all attempts to demonstrate the conversion of progestophilin B to A or to show a common precursor to both have been unsuccessful. Therefore, either the A and B receptor proteins are separate products of closely related genes or the conversion of one form to another occurs very rapidly either in vivo or in vitro.


Characterization of the avian progesterone receptor through the use of inhibitors.

Several chemical agents have been identified which block interaction of the avian progesterone receptor with isolated nuclei, ATP-Sepharose, DNA-cellulose or phosphocellulose. Four of these inhibitors, rifamycin AF/103, o-phenanthroline, aurintricarboxylic acid and pyridoxal 5-phosphate appear to block directly binding of the activated receptor complex to the above "acceptors." Another inhibitor, sodium molybdate, only blocks receptor interactions when added before receptor activation and therefore appears to interfere with the activation process. When nuclear receptor complexes were formed in vivo and labeled by nuclear exchange with [3H]progesterone in vitro, these complexes could not be disrupted by incubation of the nuclei with inhibitors. Therefore, the receptor complex bound in nuclei appears to be modified or masked in a way which resists the action of these chemical agents. These results indicate the value of inhibitors as chemical probes for the analysis of steroid receptors.


Glucocorticoid receptor cleavage by leupeptin-sensitive enzymes in rat kidney cytosol.

The proteolytic origin of small fragments of both the glucocorticoid and mineralocorticoid receptors in rat kidney cytosol was inferred from the effects of leupeptin, a bacterial tripeptide that inhibits many proteases [Sherman, M.R. et al., (1978). Federation Proc. 37:167--173]. In the present study, the smallest fragment of the glucocorticoid receptor containing the steroid-binding site, the mero-receptor, was characterized with respect to the Stokes radius (RS = 23 +/- 3 A) and the isoelectric point (pI = 5.9 at 4 degrees). Chromatography of cytosol labeled with [3H]triamcinolone acetonide on Sephadex LH-20 (Pharmacia) in aqueous buffer resolved the steroid-receptor complex from the unmodified free steroid and from steroid metabolites and contaminants. This technique facilitated analyses of the leupeptin-stabilized receptor form by isoelectric focusing (pU = 5.9 at 4 degrees) and centrifugation in glycerol gradients (s20,w = 9--11 S in 50mM KCl). When this large complex in fresh cytosol was analyzed on Agarose (Bio-Rad) at a high flow rate, it had RS congruent to 60 A in 50 mM KCl and RS congruent to 30 A in 400 mM KCl. These analytical studies with leupeptin indicate the need for inexpensive, irreversible inhibitors of proteolytic enzymes for the purification of intact receptors, holo-receptors, from kidney and other tissues. Specific proteases can then be applied to dissect the holo-receptor into the globular mero-receptor, proximal to the steroid-binding site, and the asymmetric region(s), distal segment(s), that may be involved in the nuclear interactions.


Studies on the mechanism of estradiol uptake by rat uterine cells and on estradiol binding to uterine plasma membranes.

A method for the preparation of viable uterine cell suspensions is described. Using this system the kinetics of estradiol uptake were studied in order to asses whether the steroid enters uterine cells by passive diffusion (1) or protein mediated diffusion (2). The data presented show that a) the rates of estradiol entry are nonsaturable; b) temperature dependence of uptake kinetics gives a linear Arrhenius plot; c) E2-6-CMO-BSA does not inhibit 3H-E2 uptake; d) uterine plasma membranes do not contain specific estrogen binding sites. Thus, estrogen uptake occures by passive diffusion.


Heterogeneity of AtT-20 cell glucocorticoid binding sites: evidence for a membrane receptor.

In previous studies we have found that intact AtT-20 cells contained two glucocorticoid binding sites with distinctly different affinities and specificity. In this paper, the nature of these sites was investigated by studying glucocorticoid binding to cytosol and to plasma membranes isolated from AtT-20 mouse pituitary tumor cells. Plasma membrane vesicles were isolated from AtT-20 cells and found to take up alpha-aminoisobutyric acid, indicating that they were properly oriented and functionally intact. Corticosterone bound to these vesicle in a time- and temperature-dependent manner. The binding exhibited a glucocorticoid preference since non-glucocorticoids such as progesterone, testosterone or estradiol were unable to inhibit binding. In addition, binding specificity differed from that of the cytoplasmic receptor since the synthetic glucocorticoids were also ineffective competitors. The major inhibitors of binding were corticosterone greater than 11-dehydrocorticosterone greater than 11-ketoprogesterone greater than cortisol. In other complementary studies, AtT-20 cell cytosol was tested to determine whether heterogenous soluble sites exhibiting a preference for the natural vs the synthetic steroid could also be identified. We found that binding sites for both steroid classes were approximately similar in number, specificity and behavior on ion-exchange chromatography. We conclude that, in addition to a classical soluble cytoplasmic glucocorticoid receptor, AtT-20 cells contain plasma membrane glucocorticoid binding sites. The affinity and specificity of these sites for the natural ligand, corticosterone, suggest that they play an important role in the subcellular mechanism of glucocorticoid action.


Sex steroid binding proteins in non-mammalian vertebrates.

High affinity cytosolic and nuclear steroid binding macromolecules have been identified in steroid target tissues of representative amphibians, reptiles and birds. In addition to these traditional "receptors" evidence exists which indicates the presence of other steroid binding proteins, varying in affinity and specificity, in the cytosol of steroid targets (liver, oviduct) of these same species. The possible relationships between cytosolic binding proteins of differing affinity and specificity and their relevance to hormone action in non-mammalian species is discussed.


The ovalbumin gene: transcriptional regulation by estrogen.

De novo synthesis of RNA sequences corresponding to intervening as well as to structural sequences of the ovalbumin gene have been detected in isolated oviduct nuclei. Their presence in the nuclear transcripts and their time course of induction support the hypothesis that transcription of structural and intervening sequences of the natural ovalbumin gene are regulated by steroid hormones. These results are in agreement with out previous demonstration of high-molecular-weight species of ovalbumin RNA in nuclei that contain structural as well as intervening RNA sequences and are thus likely precursors to mature cytoplasmic mRNAov. Analysis of the size of in vivo nuclear RNA by gel electrophoresis under denaturing conditions, revealed that withdrawal of hormone depletes the level of high molecular weight ovalbumin RNA as well as that of nature mRNAov and that readministration of estrogen induces the accumulation of both species. These results are consistent also with transcriptional regulation of the ovalbumin gene. In addition, they rule out the possibility that the rapid accumulation of mature mRNAov after secondard stimulation results from processing of ovalbumin RNA precursors that might have been stored in the withdrawn oviduct. We conclude that steroid hormones exert a primary effect at the level of gene transcription. Following this event, a series of coordinated cellular responses may occur which involve RNA processing, mRNA transport to the cytoplasm, protein synthesis and mRNA degradation. The final consequence of this network of molecular reactions is the induced cellular function inherent to a specific steroid hormone.


The specific binding of estradiol to the nuclear matrix.

Recent studies on the eukaryotic nucleus have described the presence of a structural component termed the nuclear matrix, that appears to be involved in nucleic acid synthesis. This study will present evidence that the nuclear matrix of both the rat uterus and chick liver contains specific, high affinity, saturable estradiol binding sites.


Heterogeneity of nuclear glucocorticoid receptor interactions.

When thymocytes are incubated with glucocorticoids at 37 degrees, 60--70% of the receptor bound steroid is associated with the nucleus. Under conditions where the rate of steroid-receptor formation is not limiting the transfer of steroid-receptors from the cytoplasm to the nucleus occurs rapidly with a T 1/2 of 30 seconds. These observations have led us to investigate whether or not all glucocorticoid receptor complexes are associated with the nucleus in the same manner. To this end, nuclear glucocorticoid-receptor complexes have been extracted by differential salt extraction and DNase I and DNase II digeston. Of the nuclear dexamethasone receptor complex initially bound, 70--75% is resistant to 0.2 M KCl extraction (designated N2) and 25--30% is resistant to 0.4 extraction (designated N4). N2 can be further extracted with 0.4 M KCl whereas N4 is resistant to reextraction with either 0.2 M KCl, suggesting that N2-N4 (N2-4) and N4 represent distinct physical forms of nuclear dexamethasone receptor. In intact cells, N2 and N4 differ under the following physiological condition. (1) N4 binding occurs prior to N2-4; (2) a cold chase of unlabeled dexamethasone decreases N2-4 by 70% but N4 binding by only 10%; (3) N4 binding decreases more rapidly than N2-4 following a decrease in hormone concentration by dilution; (4) a cold chase of either cortexolone or progesterone preferentially decreases N2-4 and has little effect on N4. In addition, the nuclear N2-4 and N4 distribution differ for cortisol, dexamethasone and triamcinolone acetonide, three steroids having different in vitro biological potencies. DNase I treatment of nuclei solubilizes approximately 60% of nuclear DNA yet releases only 20--30% of nuclear receptor, whereas DNase II solubilizes only 10% of nuclear DNA and releases 76--80% of nuclear receptor. As seen with salt extraction, the resistance of nuclear glucocorticoid-receptor complexes to a DNase I and II is dependent on the steroid molecule which is associated with the receptor. Of the steroids we have tested, nuclear triamcinolone acetonide and dexamethasone receptor complexes are most resistant to nuclease attack. Nuclear cortisol receptor complexes are readily solubilized by either DNase I or II under conditions where little dissociation of steroid from receptor occurs. These data represent evidence for physiologically distinct forms of nuclear glucocorticoid receptor interaction. In addition, they demonstrate the importance of the steroid portion of the steroid receptor in directing the nature and/or location of steroid receptors within or on the nucleus.


Estrogen control of progesterone receptor induction in human breast cancer: role of nuclear estrogen receptor.

We have provocative data which suggest that the nuclear estrogen-receptor complex interacts with DNA, that this interaction is required for appropriate receptor turnover or processing, and that processing may be essential for induction of a specific protein by estrogen. If the receptor is improperly inserted into DNA, as for instance when it is bound by nafoxidine, processing fails and the biological effect is blunted.


Electrophysiological studies on the effects of the neurotoxin apamin on cultured neurons.

Primary cultures of rat embryonic central nervous system were grown for 3 to 4 weeks in vitro. Impalement of neurons by means of high-resistance glass pipettes revealed that firing of action potentials could either be elicited by application of short square pulses or occurred spontaneously. The presence of the neurotoxin apamin caused a hyperpolarization of the membrane potential accompanied by an increase of the spike amplitude as well as an increase of membrane resistance. The significance of this effect is discussed in terms of a postsynaptic effect of this toxin.


A comparison of the carrageenan edema test and ultraviolet light-induced erythema test as predictors of the clinical dose in rheumatoid arthritis.

Twelve non-steroidal anti-inflammatory agents (NSAI's) and one steroidal anti-inflammatory agent, dexamethasone, were examined in the carrageenan edema test (CET) in the rat and in the ultraviolet light-induced erythema test (UVE) in the guinea pig to evaluate the correlation between those models of inflammation and the clinical dose of the NSAI's in the treatment of rheumatoid arthritis. The regression of the logarithm of the clinical dose with the logarithm of the ED50 for UVE gave a slope of 0.54 implying a non-parallelism of assays and a difference in mechanism. Dexamethasone failed to inhibit the UVE thereby corroborating this point. The parallelism of the logarithm of the clinical dose with the logarithm of the ED50 for the CET was substantially better (slope = 0.86). Dexamethasone was active in CET and its dose would be predicted by the CET regression. When only one variable was used for a prediction, log(CET) was a better predictor of log (clinical dose) than log(UVE). Standard methods for best regression selection indicated that even when both predictor variables were considered, log(CET) alone gave the best regression equation for predicting clinical dose. The view that inhibition of prostaglandin biosynthesis is the primary anti-inflammatory mechanism of NSAI's in rheumatoid arthritis is discussed in terms of these findings.


Studies on cell motility in inflammation. I. The chemotactic activity of experimental, immunological and non-immunological, inflammatory exudates.

The accumulation of leucocytes at the site of inflammation may be brought about by chemotaxis or proliferation in the extravascular tissues. The present paper focuses on the chemotactic properties of different types of experimental inflammatory pleural exudates, using a modified Boyden chamber. The time-course of carrageenan-induced exudate chemotactic activity for polymorphs was maximal at 4 h, thereafter diminishing towards 24 and 48 h. Chemotactic activity for mononuclear cells remained unchanged throughout the 4--48 h time-course. Heating the exudates to 56 degrees C for 1 h partially reduced chemotactic activity. These results correlate well with the migration of polymorph and mononuclear cells into the pleural cavity during carrageenan-induced pleurisy. The potency of polymorph and mononuclear cell chemotactic activity of different exudates was of the following order: carrageenan greater than calcium pyrophosphate greater than reverse passive Arthus greater than dextran. The results are discussed in order to elucidate the differences between the underlying mechanisms responsible for leucocyte accumulation in different types of inflammatory reaction.


Anti-inflammatory action following liver damage in the rat.

A high molecular weight protein fraction, obtained by column chromatography of saline extracts of the livers of rats that had previously been treated with dimethylnitrosamine, was found to have anti-inflammatory activity against carrageenin induced inflammation in the rat. Evidence was presented that the anti-inflammatory activity may be due to a protein fragment produced by proteolysis of a larger molecule.


Anti-arthritic effect of bee venom.

Bee venom, administered subcutaneously, suppressed the development of carrageenan-induced paw edema and adjuvant arthritis in the rat in a dose-related manner. A single dose of bee venom administered subcutaneously the day before or on the day of injection of complete Freund's adjuvant (CFA) effectively suppressed the development of polyarthritis. This suppressive effect decreased progressively as dosing was delayed. Bee venom was found to be most effective when mixed and injected (sub-plantar) together with CFA, the disease-inducing agent. Similarly, antigens such as egg albumin, when incorporated into CFA, and injected into the hind paw, prevented the development of arthritis. These results suggest that at least two mechanisms are involved in the anti-arthritic action of bee venom: (1) alteration of the immune response, probably via antigen competition, and (2) an anti-inflammatory action via corticosteroids or through an as yet undetermined mechanism.


Influence of vasodilators used in the therapy of heart failure on platelet aggregation.

Of the vasodilators used at present in the treatment of heart failure, only nitroprusside and phentolamine inhibit platelet aggregation at therapeutic dose levels. The other vasodilators studied, viz. nitroglycerin, isosorbide dinitrate, hydrallazine, dihydrallazine and prazosin, only inhibit platelet aggregation at relatively high concentrations, well above those reached in vivo. The exact nature of the platelet receptor, stimulation and blockade of which respectively initiate and inhibit aggregation, is not yet know, but it would appear to resemble the presynaptic alpha-receptors of other tissues.


On the nephrotoxicity of alpha-amanitin and the antagonistic effects of silymarin in rats.

In human beings, poisoning by the deathcup mushroom causes renal lesions in addition to extremely severe liver damage. It is known from animal experiments that silymarin, a polyhydroxyphenylchromanone, is capable of counteracting this alpha-amanitin-induced liver damage. The purpose of the present work was to ascertain whether renal damage could be induced in rats by giving alpha-amanitin, and whether silymarin would have any effect on such renal damage. The fact that alpha-amanitin produces pathological changes in the kidneys and that these lesions can be almost completely prevented by pretreating rats with silymarin has now been amply demonstrated by biochemical and histological techniques alike.


Therapeutic measures in allergic rhinopathy cases resistent to conventional treatment.

If medical treatment fails to cure an allergic or vasomotor rhinopathy, we have to look for surgical procedures in trying to relieve the symptoms. Vidian neurectomy is a well known technique, but there still is much discussion about the technique and the long term results. With cryosurgery of the inferior nasal turbinates we obtain a fibrosis and shrinking of these hypertrophied tissues. The nitrous oxide cryosurgery unit we use relies on the Joule-Thomson effect. The specially designed cryoprobe for intranasal procedures is against the medial wall of the turbinate for 2 minutes with freezing to between -50 degrees and -60 degrees C. Thirty-seven patients entered our study. In vasomotor rhinopathy 17 out of 24 patients were completely free of symptoms for at least 3 months, while 4 were better. In allergic rhinopathy, the results are good but we did not reach this high number of completely cured patients. Most of the patients showed a relapse after 3 to 6 months. This is probably due to a regrowth of the autonomic nerve endings. We did not note side efects in the patients included in our study.


Analysis of some functions of maternal and cord blood lymphocytes.

Various immunological investigations were performed on lymphocytes from pregnant women at the time of delivery and on cord blood cells. The results thus obtained show that: -- An appreciable number of in vitro responses to various antigens is observed among the cord blood specimens. They correlate with a corresponding positive test with the maternal blood. -- The stimulability of maternal lymphocytes to PHA and Con-A is within normal limits, whereas cord blood lymphocytes respond poorly to these two mitogens. -- The percentage of rosette forming T cells is very low in the cord blood and normal in maternal blood. -- The MLC in maternal-cord blood co-cultured show a significant inhibitory effect due to cord blood cells distinct from maternal cells. -- Cord blood lymphocytes show a normal capacity to elaborate the two lymphocytes LIF and LMF. On the other hand, the capacity of maternal lymphocytes to synthetize LMF seems to be strongly impaired. -- An inhibitory factor for PHA-stimulated mitogenic response is present in maternal serum whereas it is absent in the cord serum. -- Maternal serum IgG is significantly decreased when compared to that of normal controls. The values for IgM, IgA and IgE are within normal ranges. The cord blood IgG is slightly higher than that of the mothers. The values for IgM, IgA and IgE are very low and irregularly present.


Complement in hematological neoplasias.

Total hemolytic complement (CH50) and eight antigenic fractions of the complement system were determined in 30 patients with hematological neoplasias, distributed into the following groups: six cases of non-Hodgkin's lymphomas (NHL), seven cases of chronic lymphocytic leukemia (CLL), five cases of Hodgkin's disease (HD), seven cases of acute leukemia (AL), three cases of chronic myeloid leukemia (CML) and two cases of multiple myeloma (MM). CH50 was titred accordingly to a modification of the Kabat and Mayer method, C1q, C1s, C3, C4, C5, INHC1, C3A and properdin were determined with specific antisera by Manani and Laurell's techniques. The results obtained showed significant increase in CH50 above normal values in patients with HD, AL, and CML, especially the former, even in early stages. C1s was found to be increased in CML and AL, as well as C3 in CML. C4 is increased in CML and HD. C5 follows a course similar to C4, being also increased CLL and MM. C9 is increased in all groups, except NHL. A significant increase in C3A was found in NHL, HD and AL. There were no significant variations in C1s, INHC1 and properdin in any of the former groups. No correlation was found between clinical course and complement increase. The role of complement in neoplastic disease is discussed.


Bacterial immunotherapy in bronchial asthma.

In the treatment of bronchospastic states, primary bacterial bronchial asthma and asthmatic bronchitis, one of the most controversial aspects is the use of bacterial vaccines. In general, the treatment of these conditions is symptomatic, neglecting for the most part the existing bacterial allergy. At present, as a result of great advances in the immunotherapy of these disorders, the importance of an allergic response to bacteria in the etiology of these bronchopathies is beyond doubt. The subjects were 120 patients, 59 women and 51 men, with ages ranging from 7 to 73 years. Of this group, 21 were children less than 12 years old and all had a diagnosis of bronchial asthma or asthmatic bronchitis, with or without paranasal sinusitis, and exclusively of bacterial etiology. In order to study and evaluate the effectiveness of immunotherapy, a questionnaire, reproduced in fig. 1 was sent to the patients three years after the beginning of treatment. For this study, only the answers to this questionnaire were considered. Examination of the results shows that in bronchial disorders with bacterial allergy, treatment with bacterial vaccine achieves a 75% success rate. In the small group of children studied (a larger group is currently under investigation), the results are even more satisfactory, reaching 90.47%. It is noteworthy that the immediate reaction to the skin test was positive (++ to ++++) in 83.32% of the cases. Of the greatest importance also is the associated paranasal sinusitis in 83% of the cases, part of a sinobronchopulmonary syndrome which contributes substantially to this state of bacterial allergy. Significant side effects were found in 52.6% of the patients and consisted mainly of slight catarrhal symptoms, apparent at the beginning of treatment. At present, we have no doubt whatsoever that immunotherapy is much more valuable than prolonged symptomatic therapy in the treatment of primary bacterial bronchial asthma.


The temporal dimension in the lives of retarded adults: a problem of interaction and intervention.

This paper describes an ethnographic study of temporality among a group of 32 mentally retarded adults. Data were collected by participant observers over a period of 18 months. The findings indicate that retarded individuals may experience and employ a notion of time that varies substantially from that of mainstream American time. This results in problems of interaction and intervention between professionals and these retarded adults. Sociological concepts are proposed for understanding these interactional problems.


Egocentric speech: an adaptive function applied to developmental disabilities in occupational therapy.

This paper reviews egocentric speech as a theoretical postulate of change relevant to the practice of occupational therapy. Egocentric speech, an important adaptive behavior in normal development, designates the verbalizations that usually occur while a child between the ages of two and seven performs an adaptive task and thereby increases problem-solving abilities. The behavior is first discussed as it relates to the structures of assimilation and accommodation in Piaget's earlier sensorimotor stage, then as it appears in the preoperatory level of the concrete operations stage of intelligence. The importance of the behavior as a foundation for the inner language and thinking capacities of the adult is supported by the research of Soviet scientists Vygotsky and Luria. Finally, three case studies are presented in which egocentric speech is used in conjunction with problem-solving tasks in occupational therapy.


The immunologic response to tobacco antigens in smokers. III. Type III hypersensitivity skin reactions and specific serum precipitins to four different tobacco extracts in patients suffering from coronary artery disease.

In a population of 70 patients suffering from coronary heart disease (49 smokers and 21 non-smokers) intradermal tests and specific precipitation tests with four different extracts of tobacco were performed. Skin tests with tobacco extracts were positive in 41 smokers and 7 nonsmokers. In both groups the immediate and delayed type reactions were weak and of rather doubtful specificity, while the late type reaction was usually more frequent and stronger in smokers (in 14 patients it was positive with all preparations). Specific precipitins against tobacco antigens were found in the sera of 13 smokers but never in nonsmokers. The positive precipitation test correlated well with the positive late skin reactions to tobacco extracts. Such correlation with Ag 1 was observed in 9 out of 13 patients, with Ag II in four cases, with Ag IV and Ag V in 2 and 2 patients respectively. The coincidence of strongly positive late skin reactions and positive precipitation tests with tobacco extracts seems to indicate that tobacco allergy really exists and resembles, in a number of patients with coronary artery disease, type III hypersensitivity reactions to tobacco antigens. It is postulated that immune complexes of precipitins and tobacco antigens may be formed in some patients and initiate pathological processes in coronary arteries leading to their occlusion.


A question of professional boundaries: implications for educational programs.

During recent on-site visits a curriculum fieldwork coordinator learned that occupational therapy students were expected to use physical therapy modalities in the treatment of patients. Since the students had no academic preparation in the use of these modalities, the curriculum committee of the academic program was advised of the situation. Two academic occupational therapy programs collaborated in sending out a 48-item questionnaire to the centers currently cooperating in their fieldwork programs with the purpose of determining the kinds of modalities being used in treatment. Results of the survey showed that there was self-reported use of physical therapy modalities by occupational therapists throughout the country with greater use in some regions. The survey also showed occupational therapy involvement in new treatment areas but diminished use of some traditional therapeutic media. Guidelines are suggested regarding student involvement in new treatment areas.


Olfaction and muscle activity: an EMG pilot study.

The therapeutic significance of limbic system structures in general, and olfactory structures specifically, has been described by Fox, Ayres, Moore, and Farber in their professional presentations and publications. No data have yet been provided to substantiate claims of the effects of olfactory stimulation on muscle activity. Effects of olfactory stimulation on human muscle activity at rest were studied in seven normal children and seven normal adults. Upper trapezius, biceps brachii, rectus abdominis, and rectus femoris were monitored electromyographically for changes in muscle action potentials using peppermint oil and smelling salts in each of three positions--supine, seated quietly, and standing. Trapezius showed the greatest responsiveness in relation to other muscles. Using peppermint oil, only 18 out of 168 or 10.7 percent of the EMG recordings showed changes in muscle activity. Using smelling salts, only 21 out of 168 or 12.5 percent of the EMG recordings showed changes in muscle activity. Directional effects of peppermint oil could not be predicted, whereas stimulation with smelling salts, when effective, generally produced increased muscle activity. Children were more responsive to olfactory agents than were adults. Sex of subjects did not seem to effect the distribution of responses. When smelling salts was presented as an initial stimulus, subjects showed a greater responsiveness to all stimuli. The present data indicate that proposed effects of olfactory stimulation are more limited than was previously believed. Possible implications for clinical practice and suggestions for further study are presented.


Precipitating antibodies in sera of normal blood donors against some antigens related to type III allergy, detected by counterimmunoelectrophoresis.

Precipitating antibodies against five antigens, staphylococcus aureus, candida albicans, cotton wool dust, house dust and tetanus toxoid, related to type III allergy (Arthus reaction) were estimated in 100 sera of normal blood donors by the counterimmunoelectrophoresis technique. The three antigens staphylococcus aureus, candida and cotton wool dust exhibited rather high titres of precipitins in sera of normal blood donors, whereas nearly 80% of the sera yielded no precipitins against house dust and tetanus toxoid. For diagnostic purposes the borderline titres were estimated as follows: 1:8 for staphylococcus aureus, 1:16 for candida albicans and 1:8 for cotton wool dust. Even low titres with the house dust antigen indicated a pathogenic situation.


Insects as inhalant allergens.

The importance of insect dust as inhalant allergen (e.g. locust, cockroach, mite, butterfly, bee, fly, etc.) is frequently underestimated as a cause of allergic conjunctivitis, rhinitis and bronchial asthma. The high allergenic potency of insect dust is demonstrated in cases of occupational allergy against locust. This dust is an obligatory sensitizing agent depending upon the degree of exposure and the potency of the allergen irrespective of constitutional factors. No doubts exist any more about the importance of house-dust mite (Dermatophagoides pteronyssinus) as an inhalative allergen. Allergy analysis should be extended also to these insect allergens especially in unclarified cases of perennial and particularly seasonal bronchial asthma or its "equivalents" (atopic rhinitis and conjunctivitis).


Activity guidelines for early subacute and high-risk cardiac patients.

Research in exercise physiology indicates that energy cost can only be used as a rough index in the selection of activity for cardiac patients because it does not accurately predict the cardiac stress associated with any given activity for any given individual. A framework is presented in this paper for occupational therapy assessment of function in the cardiac patient based on determination of cardiac stress with activity through skilled clinical observation employing telemetry EKG, auscultation, and blood pressure recording. Clear activity guidelines are then formulated, using a scientific data base and including modification of activity to reduce cardiac stress. The procedure for skilled clinical observation of function in cardiac patients is described and data are presented from the use of this procedure to evaluate early subacute and high-risk cardiac patients during self-care in an acute hospital.


Learning patterns of young children with above-elbow prostheses.

In order to develop an improved method of teaching young child amputees to operate the forearm lift and elbow lock of a conventional above-elbow prosthesis, learning patterns of 12 young above-elbow amputees were observed and described by occupational therapists. From these observations, signs of readiness for learning were identified and a method was proposed for teaching these controls to children. The therapist gave the child physical assistance as well as verbal instruction and a demonstration for each part of the operation and then for the combined motion. Application to activities required development of new habit patterns and appeared to be related to cognitive abilities beyond the sensorimotor level. Mechanical features of the double cycle lock tended to complicate learning and demonstrated the need to develop an elbow lock mechanism that better meets the needs of children.


The use of life review activity with confused nursing home residents.

Reminiscing and life review are adaptive tasks of old age. This article describes an occupational therapy group program for confused nursing home residents designed to facilitate reminiscing and promote the review process. Results of the study indicate that behaviors of confused residents improved during group meetings and that participants who attended most frequently showed the greatest change in behavior.


Comparison of three positions for evaluating the asymmetrical tonic neck reflex.

Twenty-four males ages 8 to 11 were videotaped while being tested in three positions for the ATNR: quadruped with the head passively rotated to either side; standing with the arms outstretched and eyes closed with the head passively rotated to either side; and quadruped reflex inhibiting posture with the skull hand on the hip and the face knee off the floor and with the head actively rotated to either side. Three "expert" raters viewed the edited tape and rated each subject in each position using a protocol devised for the study. The results suggest that the quadruped reflex inhibiting posture more readily reveals the presence of the reflex when compared to the other positions, in this population of learning-disabled children.


Association between nystagmus hyporesponsivity and behavioral problems in learning-disabled children.

This study explored the hypothesis that an association exists between postrotary nystagmus hyporesponsivity and behavioral problems in learning-disabled children. Supporting this conclusion was the finding that the learning-disabled boys rated by teachers as displaying the most socially inappropriate behaviors had significantly lower postrotary nystagmus durations than other learning-disabled boys. In addition, near significant associations were obtained between subnormal nystagmus functioning and socially inappropriate responding for boys and girls combined. Learning-disabled girls were evaluated as responding significantly more appropriately than learning-disabled boys, while having significantly shorter postrotary nystagmus durations; thus, sex of a child may be an important variable in determining relationships between psychological characteristics and hyporesponsive nystagmus. Additional research is needed in this area because of a number of limitations to this study; however, these results present further suggestive evidence that learning-disabled children can be categorized according to characteristics of their postrotary nystagmus.


The quality of care in occupational therapy: an assessment of selected Michigan hospitals.

In this study, a methodology was developed and tested for assessing the quality of care in occupational therapy between educational and noneducational clinical settings, as measured by process and outcome. An instrument was constructed for an external audit of the hospital record. Standards drafted by the investigator were established as normative by a panel of experts for use in judging the programs. Hospital records of 84 patients with residual hemiparesis or hemiplegia in three noneducational settings and of 100 patients with similar diagnoses in two educational clinical settings from selected Michigan facilities were chosen by proportionate stratified random sampling. The process study showed that occupational therapy was of significantly higher quality in the educational settings. The outcome study did not show significant differences between types of settings. Implications for education and practice are discussed.


Feedback goniometers for hand rehabilitation.

Active range-of-motion exercises and related activities are an important means for applying progressive stress to induce remodeling of various tissues that restrict range of motion in the hand and wrist. Supplying joint angle feedback to patients as they exercise can help them more consistently to reach the flexion/extension goals set by the therapist. To accomplish this aim, feedback goniometers have been developed that are worn on the hand during exercise and therapeutic activities. These devices supply a threshold feedback signal when a predetermined joint angle is attained. Clinical trials indicate that many patients in a comprehensive hand rehabilitation program after injuries or corrective surgery will improve somewhat more in active range of motion if they use feedback goniometers while exercising. Plans are available for fabricating such devices from readily obtained tools and parts at a modest cost.


Aspirated foreign bodies in children.

Children six months to four years of age are at greatest risk for aspiration of foreign bodies. A history of coughing after contact with small objects is the most important clue. The clinical presentation varies from paroxysms of choking and coughing to chronic cough or wheezing. Chest radiographs are normal in up to one-half of the children. The location and size of the foreign body determine the urgency and selection of therapy. Prevention and a high index of suspicion will decrease morbidity.


Superimposed encephalopathy in the psychotic patient.

Encephalopathy (acute organic brain syndrome) superimposed on functional psychosis may be overlooked because the physician assumes that any exacerbation is due to fluctuation in the psychosis. Correct diagnosis requires a high index of suspicion and a firm knowledge of the signs of encephalopathy. A careful diagnostic approach permits the recognition of encephalopathy and separates it from functional disorders such as schizophrenia.


Current heart valve prostheses.

Current heart valve prostheses may be classified as either mechanical or tissue valves (bioprostheses). The principal advantage of mechanical devices is their established long-term durability; however, chronic anticoagulation is recommended to reduce the incidence of thromboembolic complications. Tissue valves are associated with a relatively low rate of thromboembolism but their durability level has not been determined. All contemporary prosthetic heart valves yield comparable survival rates.


Predicting results of coronary angiography.

This study compares the ability of various risk factor combinations to predict the extent of coronary artery disease found on coronary angiography. Risk factors were measured in 99 patients prior to coronary angiography. Clinical, epidemiological, psychosomatic, and combined orientations were compared as to their ability to predict angiography results. The clinical orientation was the most successful in predicting vessel disease (p less than .0001), followed by the epidemiological model, which was also successful (p less than .03). In contrast, psychosomatic factors were not accurate predictors of vessel disease. By combining all of the orientations, the accuracy of prediction is improved.


Pervenous retrieval of embolized catheters from the right heart and pulmonary arteries.

Successful removal of embolized or retained catheter fragments from the right heart was achieved in two out of four patients using pervenous catheter techniques. For the first time a fragment, radiolucent on image intensification, was retrieved from the right pulmonary artery using a wire snare. In a second case a hook-loop was made in the right ventricle with a Judkins left femoral coronary angiographic catheter, which has advantages over previously described hooking devices, to withdraw a fragment to the iliac vein for subsequent snaring. Failure of retrieval occurred only in specially difficult circumstances; when a catheter embolized to the pulmonary artery of a Tetralogy of Fallot, and when in spite of successful ensnarement, a fractured electrode was firmly adherent to the right ventricular apex. Successful pervenous retrieval may require a combination of techniques which move or dislodge, such as a hook or balloon combined with those which ensnare, such as a wire loop or bioptome. Using such techniques, with minimal additions to standard equipment, retrieval procedures can be offered as a routine cardiac catheterization service with a high rate of success.


Incidence of mitral valve prolapse in one hundred clinically stable newborn baby girls: an echocardiographic study.

Clinical and echocardiographic examinations were performed on 100 clinically stable, newborn baby girls. Mitral valve prolapse was noted on the echocardiograms of seven babies. Three subjects had systolic clicks, two of whom had systolic murmurs following the click. The four other babies who had echocardiographic evidence of mitral valve prolapse had no abnormal auscultatory signs. Of the 93 babies without evidence of mitral prolapse, 91 had normal echocardiograms and auscultatory features; one was noted to have a murmur consistent with a ventricular septal defect, and another had an eccentric aortic valve on the echocardiogram which was suggestive of a bicuspid aortic valve. Serial studies on our group of subjects will yield useful information regarding the natural history of mitral valve prolapse.


Electrophysiological effects of disopyramide phosphate during experimental myocardial ischemia.

In order to correlate the antiarrhythmic and electrophysiological effects of disopyramide phosphate during acute myocardial ischemia, we performed experiments in 17 mongrel dogs. Refractory periods obtained by the extrastimulus method and conduction times recorded from local electrograms were determined in potentially ischemic and nonischemic areas prior to, after left anterior descending coronary occlusion, and following intravenous administration of disopyramide phosphate 3 mg./Kg. Control refractory periods were similar in both nonischemic and ischemic areas. Following coronary ligation, a disparity of refractoriness of 28 msec. was induced between these two areas. After disopyramide administration, this disparity was reduced from 28 msec. to 5 msec. (p less than 0.001) after 5 to 15 minutes, and to 15 msec. (p less than 0.01) after 15 to 30 minutes. Coronary ligation prolonged conduction times by 8 msec. (p less than 0.005) in ischemic areas and disopyramide further prolonged conduction in these areas by an additional 9 msec. (p less than 0.001). A minimal and transient prolongation of conduction was present in nonischemic areas. We conclude that the differential effects exerted by disopyramide phosphate in ischemic areas may explain its suppressant action of arrhythmias of ventricular origin.


Spontaneous resumption of sinus rhythm in an elderly patient after 13 years of permanent atrial fibrillation.

One female patient--with slight pure mitral stenosis, mild hypertension and ischemic cardiomyopathy and disabling pulmonary emphysema--developed at 54 years of age permanent atrial fibrillation, had a gratuitous mitral commissurotomy four months later, sustained chronic fibrillation for 13 years, then spontaneously resumed sinus node command at age 67 without any discernible reason. Sinus rhythm was being maintained at follow-up nine months later. Her cardiac status of fair compensation under modest digitoxin and diuretic therapy has neither improved nor worsened with the return of atrial systole. The duration, in this observation, of permanent auricular fibrillation before spontaneous return of sinus rhythm, is one of the longest ever published, exceeded, to the best of my knowledge, only by one case of Lewis and by another one of Reeve and associates. Such an exceptional event points out a fascinating enigma: how can major longstanding atrial dysrhythmias (fibrillation, flutter), whose causes and pathogenesis seem at least partly elucidated, spontaneously disappeer in atria so badly diseased? I think we must humbly confess that no satisfactory explanation is at present available for this disconcerting phenomenon.


Traumatic pulmonary artery--left atrial fistula: an unusual case of cyanosis in an adult.

Eighteen months after sustaining a stab wound to the left upper chest, a 59-year-old man presented with cyanosis and extertional dyspnea. Arterial desaturation due to a central 22 per cent right-to-left shunt was present. A selective pulmonary arteriogram demonstrated a fistula between the main pulmonary artery and the left atrium. At operation the fistula was closed. A laceration of the pulmonic valve and healed pericarditis were present. Marked symptomatic improvement followed the operation, but a murmur of pulmonic valvular regurgitation persisted. The fistula and laceration of the pulmonic valve were probably traumatic in origin.


Developing and implementing an industrial hygiene and safety program in industry.

The development and implementation of a comprehensive industrial hygiene and safety program is a complex activity for which there does not exist a uniform code or set of guidelines. Although the ultimate goal of such a program is to provide for the welfare of the employee through the use of engineering control and other preventive measures, there is great variation among business establishments on methods necessary to attain this result. Factors which contribute to this variation usually are: type of industry, management philosophy and size of the business establishment. This paper addresses many key elements integral to this activity such as justification and philosophy, organizational reporting relationships, interfunctional communication, technical and personnel requirements and program performance indicators.


Quantitative fit-test method for powered air-purifying respirators.

The fit-test method for powered air-purifying respirators described here allowed quantitative determination of the leakage of PAPRs that offered PFs ranging from 50 to greater than 10,000. Five types of PAPRs were tested on 10 subjects selected from a test panel representing a wide range of facial sizes. PAPRs tested provided all subjects with PFs of 1000 or greater when operated with the blowers on, while PFs observed with the blower off, for two tight-fitting facepieces, ranged between 50 and 100. The exercises used in these test procedures are believed to be typical of movements made by persons wearing respiratory protective equipment and performing light work. Studies of PFs obtained by workers wearing respiratory protective equipment in industry would be necessary to establish how well the developed laboratory test methods predict the level of protection offered to workers wearing the equipment.


Electromagnetic radiation emitted from video computer terminals.

There has been a developing concern about potential health hazards attributable to electromagnetic radiation from video computer terminals. Since users of these devices typically spend many hours daily in close proximity, they would be subject to chronic long-term exposures to any emitted radiation. Radiation was detected at frequencies ranging from 1.5 kHz to 1,420 MHz in the RF portion of the EM spectrum and from 350 nm to 600 nm in the ultraviolet and visible region. However, the levels were far less than the most restrictive permissible exposure levels established by any agency or government of any nation. There is no experimental or epidemiological evidence presently available to indicate that these levels of RF radiation have any deleterious effects on the human biological system.


Respiratory retention and acute toxicity of furan.

The respiratory tract retention of furan has been studied in dogs as part of a broad investigation of compounds found in the vapor phase of cigarette smoke. The LD50 of furan has also been determined in mice and rats and the LC50 in mice. Respiratory uptake of furan was between 90 and 95%, varying inversely with the ventilatory rate. Retention was not affected by tidal volume changes but was directly related to concentration inhaled. Intraperitoneal LD50 values were 5.2 mg/kg for rats and 7.0 mg/kg for mice. The LC50 for mice was 0.12 microgram/mL. These results indicate the high toxicity of furan and that it is readily absorbed by the inhalation route.


Service station attendants' exposure to benzene and gasoline vapors.

Service station attendants' exposure to benzene, based on 85 TWA results at 7 stations, were well below 1 ppm except one exposure of 2.08 ppm. Short term exposures were 1.21 ppm or less over 15 minutes. Attendants' TWA exposures to total gasoline vapor were 114 ppm or less, with measured 15 minute exposures no higher than 100 ppm during actual filling operations. One station had vapor recovery nozzles; exposures here were below the detectable level (0.01 ppm benzene) on 10% more days than the next lowest station. Still, the magnitude of overall exposures and the degree of reduction indicate that vapor recovery is not needed to control exposures. Some attendants had consistently higher exposures than others. This is felt to be due to work practices, such as standing close to the fill opening, plus local wind conditions around the car as it is filled with gasoline.


Respirable particulates generated by pressurized consumer products. I. Experimental method and general characteristics.

Many products and materials are available in the widely used pressurized package or "aerosol" form. A simulated breathing zone model approach has been developed and used to characterize the particles to which a user may be exposed. Some products characterized under simulated "worst reasonable" conditions produced concentrations of particulates smaller than 6 micrometer aerodynamic diameter exceeding 50 mg/m3.


Respirable particulates generated by pressurized consumer products. II. Influence of experimental conditions.

The many products available in pressurized packages produce appreciable concentrations of particulates that may be deposited in the deep lung of human users. We have reported the size and concentration characteristics of these aerosols under carefully standardized conditions in a previous paper. These standard conditions have been varied to determine the influence of product discharge conditions on observed aerosol characteristics. The size characteristics are relatively insensitive to a wide range of changes in the discharge conditions; the only significant effect observed followed changing the target of the spray from a steel plate to a wig. The aerosol concentrations were changed by several experimental factors, but the relative changes were less than the estimated relative range of human exposure.


Coexistence of ventricular parasystole and ventricular couplets: mechanism and clinical significance.

In 78 consecutive patients with uniform ventricular ectopic complexes and without heart disease, ventricular couplets were present significantly more often when the coupling interval of ventricular ectopic complexes was variable than when it was fixed (P less than 0.04). In 69 consecutive patients with couplets, the prevalence of a variable coupling interval was significantly greater than that of (55 versus 14 cases; P less than 0.001). Among 55 patients with a variable coupling interval, ventricular parasystole was probable in 38 and possible in 17 patients. These results suggest that the association between ventricular couplets and parasystole is not coincidental. Of several possible mechanisms responsible for this association reentry within the parasystolic focus or its vicinity is the most probable. This may explain the observation that the couplets are seldom followed by consecutive ventricular ectopic complexes or ventricular tachycardia. If this hypothesis is correct, the clinical significance of ventricular couplets in the presence of ventricular parasystole may be similar to that of single reentrant ventricular ectopic complexes.


Interatrial conduction (activation) times.

Left atrial electrograms were recorded simultaneously from sites located in the coronary sinus, right pulmonary artery and esophagus in order to determine and correlate the interatrial conduction times obtained from these locations. Ten patients with normal-sized atria and 16 patients with isolated left atrial enlargement were studied. A high correlation existed between the P wave duration and the interatrial conduction times obtained from the coronary sinus and pulmonary artery; good correlations were also found for the interatrial conduction times recorded from the pulmonary artery and esophagus correlated well with those recorded from the distal coronary sinus (the generally accepted standard for the indirect interatrial conduction time measurements). In addition to providing information on the mechanism of atrial arrhythmias, the electrograms obtained from the various indirect left atrial recording sites provide satisfactory quantification of interatrial conduction.


Assessment of early ventricular systole by first pass radionuclide angiography: useful method for detection of left ventricular dysfunction at rest in patients with coronary artery disease.

To identify abnormal left ventricular function without exercise stress in patients with coronary artery disease first-pass radionuclide angiograms were analyzed in 32 normal subjects (Group I); 31 patients with coronary disease and normal contrast ventriculograms (Group II); and 17 patients with coronary disease and depressed left ventricular function (Group III). Total ejection fraction (EF) was computed with standard angiographic methods and from each time-activity curve. During the first third of systole, ejection fraction was determined manually by averaging three to five beats and the value compared with that obtained with contrast ventriculography: (Formula: see text). Both total radionuclide ejection fraction (r = 0.95) and first-third ejection fraction (r = 0.91) correlated well with angiography. Intraobserver and interobserver variation was small, averaging 0.02 +/- 0.02 (range 0 to 0.05). The radionuclide first-third ejection fraction was 0.25 or greater in normal subjects and less than 0.25 in 29 of 31 patients (94 percent) in Group II and in all patients in Group III. It is concluded that the first-third ejection fraction obtained with first pass angiography identifies subtle abnormalities of left ventricular function at rest in more than 90 percent of patients with coronary disease that may not be recognized by total ejection fraction alone.


Echocardiographic assessment of the adequacy of pulmonary arterial banding.

Thirty-one echocardiograms of 21 patients who had pumonary arterial banding were analyzed to assess the aequacy of surgery. In 5 patients the echocardiograms were obtained before and after banding and in 16 patients only after surgery. Right and left ventricular systolic time intervals were measured echographically. The ratios of the right ventricular preejection period to right ventricular ejection time (RPEP/RVET) were correlated with both diastolic (r = 0.94) and systolic (r = 0.86) pulmonary arterial pressures distal to the band. The analysis of right ventriclar systolic time intervals, especially the RPEP/RVET ratio, clearly differentiated patients with an adequate band (distal pulmonary arterial diastolic pressure less than 15 mm Hg) from patients with an inadequate band (distal pulmonary arterial diastolic pressure equal to or greater than 30 mm Hg). The results indicate that echocardiography is a useful noninvasive tool in evaluating the adequacy of the pulmonary arterial band and facilitates the follow-up of patients after banding.


Incessant atrial tachycardia in childhood: association with rate-dependent conduction in an accessory atrioventricular pathway.

A detailed electrophysiologic study in a 7 year old boy with incessant atrial tachycardia revealed the presence of an atrioventricular pathway conducting only in the ventriculoatrial direction. The results indicate a reentrant mechanism with the retrograde limb of the circuit entering the atrium in the region of the proximal to mid coronary sinus. The accessory pathway exhibited relatively long conduction times and conduction properties suggesting decremental conduction. Thus, an electrophysiologically atypical anomalous conduction pathway may be responsible for the occurrence of incessant atrial tachycardial in some children.


Systolic hypertension: hemodynamic mechanism and choice of antihypertensive treatment.

Arterial compliance and indexes of ventricular ejection were measured in 27 men with systolic hypertension. The patients were separated into two age groups, younger or older than age 35 years, and matched with normotensive control subjects. Arterial compliance was estimated from analysis of the monoexponential blood pressure-time curve during diastole, according to a simple viscoelastic model. In the younger patients, arterial compliance and stroke volume were within normal ranges. Rapid ejection time was significantly reduced (P less than 0.001), indicating an increased venlocity in the first part of ventricular ejection. Systolic pressure decreased significantly after administration of propranolol, which also caused prolongation of rapid ejection time. In the older patients, indexes of ventricular ejection were within normal limits. arterial compliance was significantly reduced (P less than 0.01) and was negatively correlated with the level of systolic pressure (P less than 0.001). Systolic pressure decreased significantly after administration of sodium nitroprusside, which caused an increase in arterial compliance. These findings provide evidence that: (1) the hemodynamic mechanisms of systolic hypertension differ in younger and older patients, and (2) these hemodynamic differences should be taken into account when choosing drugs to decrease systolic pressure.


Suppression of ventricular arrhythmias with intravenous disopyramide and lidocaine: efficacy comparison in a randomized trial.

Twenty-six patients with clinically significant ventricular arrhythmias were randomly assigned to treatment with either intravenous disopyramide or lidocaine; crossover to the other agent was permitted in nine cases of primary drug failure. In addition, disopyramide was administered nonrandomly to seven patients with ventricular arrhythmias not controlled by lidocaine in standard doses. Arrhythmia control (greater than 50 percent reduction of premature ventricular complexes) was achieved in all 22 trials with disopyramide and in 9 of 13 trails with lidocaine in the random study, whereas clinical efficacy (arrhythmia control with absence of side effects) occurred respectively in 15 of 22, and 8 of 13 trials. In all 11 patients (7 nonrandom, 4 random) whose arrhythmia was not controlled with lidocaine the arrhythmia was controlled with disopyramide. Thus, the clinical efficacy of intravenous disopyramide ran parallel to that of lidocaine in patients with ventricular arrhythmias. Furthermore, intravenous disopyramide was an effective alternative agent for patients with arrhythmia not controlled by lidocaine.


Clinical electrophysiologic effects of encainide, a newly developed antiarrhythmic agent.

Encainide is a newly developed antiarrhythmic agent. With the use of intracardiac electrophysiologic techniques, its effects on the cardiac conduction system were examined in 10 patients with coronary artery disease. Five patients received 0.6 and five received 0.9 mg/kg body weight of encainide intravenously over 15 minutes. Plasma concentration, heart rate, blood pressure and conduction intervals (A-H, H-V, QRS and Q-T) were measured before, during and after encainide infusion. In addition, sinus nodal recovery time, Wenckebach cycle length, and atrial, atrioventricular (A-V) nodal and right ventricular refractory periods were measured before and after encainide infusion. The average peak plasma concentration was 0.49 +/- 0.35 microgram/ml (mean +/- standard error of the mean). Encainide significantly prologned H-V and QRS intervals in all patients by an average of 31 +/- 7 and 18 +/- 9 percent (standard deviation) (P less than 0.001), respectively. A minimal increase in the Q-T interval was also observed after encainide infusion (2 +/- 9 percent, P less than 0.01), but no significant changes were noted in heart rate, blood pressure, A-H interval, corrected sinus noal recovery time, Wenckebach cycle length or refractory periods of the atrium, A-V node or right ventricle. It is concluded that encainide significantly prolongs conduction in the His-Purkinje system without affecting conduction or refractoriness of other parts of the cardiac conduction system in man.


Prenatal closure of the foramen ovale in complete transposition of great vessels. Observations in a case with intact ventricular septum and normally developed left heart chambers.

A rare case is reported of premature closure of the foramen ovale in d-transposition of the great vessels with intact ventricular septum and normal development of the left side of the heart. Asphyxia neoatorum and cardiac failure were the manifestations in the early neonatal period. Balloon atrial septostomy during cardiac catheterization would be unsuccessful in infants with this condition, and closed atrial septectomy (Blalock-Hanlon procedure) would be necessary for survival.


Subdivision of mouse vibrissae on an embryological basis, with descriptions of variations in the number and arrangement of sinus hairs and cortical barrels in BALB/c (nu/+; nude, nu/nu) and hairless (hr/hr) strains.

Development of vibrissae was studied in dd/y mouse embryos by scanning electron microscopy. Arrangement of vibrissae and cortical barrels were also studied by light microscopy in adult dd/y, BALB/c(nu/+), nude (BALB/c, nu/nu) and hairless (hr/hr) mice to find genetic or epigenetic variations. Rudiments of vibrissae first appear on Day 12 of pregnancy as longitudinal ridges on the developing muzzle, and each hair rudiment is represented by a dome on the ridges. The dorsal two rows (A and B; Woolsey and Van der Loos, '70) of mystacial vibrissae are on the lateral nasal prominence, while the ventral three (C, D and E) are on the maxillary prominence. Smaller hairs of mystacial vibrissae appear at the labial part of the maxillary prominenceon Day 13. The rudiments of rhinal hairs also appear at this stage on the part of the muzzle derived from the medial nasal prominence. Thus the so-called mystacial vibrissae should be subdivided into three (or 4, including the rhinal) groups on an embryological basis. They are the lateral nasal, the maxillary and the labial. A supernumerary sinus hair and a corresponding barrel was observed between D and C rows uni-or bilaterally in one third of individuals of BALB/c, nude and hairless mice. It is suggested that supernumerary hairs tend to occur between the groups of hairs as defined above. In nude and hairless mice small barrels representing labial hairs are diminished in number. The number of hair follicles, however, is normal.


Development of lamellar bodies and subsurface cisterns in pyramidal cells and neuroblasts of hamster cerebral cortex.

In pyramidal cells of hamster frontal cortex lamellar bodies and subsurface cisterns sequentially occurred during development from newborn to three months of age. Neither of these two specializations of the rough endoplasmic reticulum was seen in neurons of the newborn. The first specialization that we observed was the subsurface cistern, which appeared at five days and showed a significant increase both in frequency and in length throughout development. The lamellar body was first seen at ten days of age. This specialization showed a peaking of frequency, length, and number of cisterns per body at 15 days, which subsequently decreased gradually to 3-month-old levels. The occurrence of lamellar body-subsurface cistern complexes increased with age. We suggest that the lamellar body may be an ER specialization that is involved in an increased and/or stage-specific protein synthesis in the young prior to the final maturation of the usual neuronal protein synthetic organelles, and that in the 3-month-old neurons, the lamellar body may be involved in modifying, storing or transporting metabolites received from the neuropil components via the subsurface cisterns. The subsurface cistern, on the other hand, by virtue of its location subjacent to the neuronal plasma membrane and of its increased frequency from birth to maturation, may be involved in the exchange of metabolites and nonsynaptic forms of communication at all ages.


Development of the renal corpuscle during metamorphosis in the lamprey.

The renal corpuscle of the adult lamprey, Petromyzon marinus L., is formed during the programmed period of metamorphosis. Development is initiated early in this metamorphic period and is marked by the synchronous formation and growth of rudimentary nephron units (RNU) from longitudinal cord of nephrogenictissue extending from the posterior tip of the degenerating larval kidney to the cloaca and connected to the peritoneal epithelium. Detachment of the RNU from the peritoneum involves autolysis and cell death and is accompanied by their branching into five or six hexagonally-arranged nephrons which radiate from the original point of attachment. Differentiation of the epithelial cells at the proximal ends of the nephrons is preceded by the widening of lateral intercellular spaces, the formation of tubular lumina (primitive urinary spaces), the loss of apical cell junctions, and the development of a capillary network with its associated mesangium. With the extension of the capillaries and mesangium between the proximal ends of adjacent undifferentiated nephrons, visceral epithelial cells (podocytes), with long cell processes (trabeculae) and slit membranes, make their appearance. The urinary spaces resulting from this form of development are lined by the epithelium of the dilated ends of the nephrons (nephric capsules). The cells of these capsules differentiate mainly into podocytes, but a few parietal cells connect to the draining tubule. This method of development explains the unique form of the renal corpuscle in the adult lamprey. Despite the type of morphogenesis, this renal corpuscle possesses the fine-structural features seen in the renal corpuscles of other vertebrates.


The association of amorphous mineral deposits with the plasma membrane of pre- and young odontoblasts and their relationship to the origin of dentinal matrix vesicles in rat incisor teeth.

Young and preodontoblasts and matrix vesicles which occur in the presecretory region of incisor teeth of growing rats were examined in stained and unstained ultrathin sections in order to characterize sites involved in the initial mineralization of dentin. Common to pre- and young odontoblasts in the presecretory region were hemispherical membrane-associated amorphous densities, measuring 5-35 nm in diameter after fixation in glutaraldehyde-osmium tetroxide or glutaraldehyde only. Amorphous densities were associated also with the limiting membranes of some vesicles in the extracellular matrix. Other vesicles in the extracellular matrix contained needle-like crystalline deposits typical of dentinal matrix vesicles. Fully differentiated odontoblasts in more incisal regions of the tooth lacked plasma membrane-associated amorphous densities. Neither amorphous nor crystalline densities were associated with any other cellular or subcellular structures in cells of the presecretory region. Flotation of ultrathin sections on solutions of EDTA or EGTA removed the amorphous densities from the plasma membranes, suggesting that the amorphous densities are calcium-containing mineral deposits. Amorphous deposits were associated with the membrane of vesicular structures protruding from the surfaces of pre- and young odontoblasts, suggesting that vesicles found in the extracellular matrix arise by budding from the plasma membranes of pre- and young odontoblasts. The occurrence of amorphous mineral deposits in association with the limiting membrane of some vesicles in the extracellular matrix, and the occurrence of needle-like mineral crystals within other matrix vesicles, suggest that an amorphous-to-crystalline phase transformation of mineral takes place within the matrix vesicle. The results of this study suggest that calcium-binding sites associated with plasma membranes of pre- and young odontoblasts act as nucleating centers for primary mineral deposition in tooth dentin.


The prism pattern of rat molar enamel: a scanning electron microscope study.

Rat molar enamel has been studied by sectioning the enamel along various planes, and observing the etched surfaces in the SEM. It was found that the prism pattern was much more variable than in rat incisor enamel. Regions without prism decussation seemed to dominate in the occlusal half of the molars. Where present, prism decussation was of the uniserial lamellar type, but it varied considerably in distribution, extent, and distinctness. Prism decussation seemed to have a predilection for the cervical enamel, and was almost absent in the enamel on the occlusal surface. The interprismatic substance showed a characteristic configuration: In the inner enamel it appeared in the form of radially oriented sheets, which tended to delimit radially directed, single lines of prisms. In regions with prism decussation these single lines of prisms encompassed prisms belonging to different prism lamellae. In the outer part of the enamel the interprismatic substance exhibited a honeycomb appearance. The similarities and differences between the prism patterns of rat incisor and molar enamel may be of importance for understanding the mechanisms of amelogenesis, especially for the recognition of factors controlling the movement of ameloblasts.


Observations on the inter-relationships of Sertoli cells at the level of the blood- testis barrier: evidence for formation and resorption of Sertoli-Sertoli tubulobulbar complexes during the spermatogenic cycle of the rat.

Structures termed tubulobulbar complexes are known to be formed by adjoining Sertoli cells at the level of the blood-testis barrier (Russell and Clermont, '76). Here, long (2-4 micrometer) tubular evaginations of one Sertoli cell, which end in bulbous dilations, are seen in corresponding invaginations of a neighboring Sertoli cell. In most regions of the tubular and bulbous portions of the complex, the Sertoli plasma membranes were found to be separated by a 4-5-nm intercellular space, but in some areas the membranes converged to form tight and gap junctions. The numbers, distribution and properties of tubulobulbar complexes were studied in relation to the cycle of the seminiferous epithelium. From the data obtained it was concluded that tubulobulbar complexes develop and undergo regressive changes during the spermatogenic cycle. Most complexes arise during the early stages of the cycle (Stages II-V) and develop large bulbous endings. Developing tubulobulbar complexes consist of short evaginations of one Sertoli cell which face a bristle-coated pit of the opposing Sertoli cell. At midcycle (Stages VI-VII) most show regressive changes and are eventually resorbed as a consequence of the action of nearby Sertoli lysosomes. Once resorbed, the probability of seeing a tubulobulbar complex in thin sections decreases from 4- to 8-fold. The few tubulobulbar complexes which remain past this period (Stages VII-XIV-I) usually lack bulbous endings and are fequently seen above type A spermatogonia. The data suggest that small fragments of cytoplasm and plasma membrane (including junctional surfaces) are lost from one Sertoli cell as a result of the degradative processes occurring in a neighboring Sertoli cell. Tubulobulbar resorption is discussed in relation to the impending breakdown of the blood-testis barrier above spermatocytes as these cells move upward. The possible significance of the cyclic resorption of tight and gap junctional sites between Sertoli cells is also discussed.


Maturation of rabbit auricular chondrocytes grown in vitro in monolayer culture.

Chondrocytes isolated from auricular cartilage of 7-day-old rabbits were grown in vitro until the onset of phase III, occurring after 10-14 population doublings (PD). The size of cells and their dry mass were measured at various PD levels. These data were compared with results of analogous measurements of chondrocytes freshly isolated from 28-day-old rabbits. Both in vivo, during cartilage growth, and in vitro, some of the chondrocytes increased considerably in size and acquired two nuclei. Chondrocytes cultured in vitro for 4 population doublings were still capable of depositing elastic fibers in culture and forming cartilage after intramuscular transplantation. After longer periods of cultivation the ability of cells to produce a cartilage matrix declined. It is suggested that the auricular chondrocytes may represent a convenient model for comparative studies of cell aging in culture and in vivo, owing to the simplicity of matching senescent cells arising in both these situations.


The superior olivary complex in C57BL/6 mice.

The cellular and cytoarchitectural features of the lateral superior olive, the medial superior olive, the superior paraolivary nucleus and the medial, lateral and ventral nuclei of the trapezoid body are described in C57BL/6 mice using Nissl, Bodian and Golgi techniques. Principal, spindle and marginal cells are present in a well-defined lateral superior olive. The dendrites of these cells run primarily within rostrocaudal sheets as in the cat. The principal cells of the medial nucleus of the trapezoid body are similar to the principal cells in the cat. Large multipolar cells characterize the lateral nucleus of the trapezoid body and bipolar cells with a medial-lateral orientation are found in the medial superior olive. The largest neurons are found in the superior paraolivary nucleus and the lateral superior olive, and the medial and ventral nuclei of the trapezoid body. While brain weight and neuronal packing density change with development, the characteristic location of cell groups and the shape and Nissl-staining pattern of neurons in the youngest brains examined were essentially unchanged in the adult mice, although dendritic maturation had occurred. The homologies of the C57BL/6 superior olivary complex nuclei with the same areas described in other mouse strains, rat and cat are discussed. This study expands our understanding of the organization of the superior olivary complex in an inbred strain of Mus musculus and relates it to other species. The data about changes occurring during postnatal maturation may aid in the interpretation of behavioral and physiological studies of neonatal plasticity of the auditory system.


Successful maintenance of suckling rat ileum in organ culture.

Ileum from rats 4, 9, 11, 12, and 15 days old can best be maintained for 24 hours in a system using Hanks' Balanced Salt Solution without fetal calf serum, at 25 degrees C and 21% O2. Suckling rat duodenum and jejunum were difficult to maintain well for 24 hours in this system or a variety of other systems that were tried. A temperature of 37 degrees C hastened deterioration of duodenum, jejunum or ileum. With ileum, 3H-thymidine and 14C-leucine were increasingly incorporated into DNA and protein over the 24-hour period. Light microscopy, as well as scanning and transmission electron microscopy, showed very good preservation of the ileum after 24 hours. The addition to the medium of hydrocortisone, 1 micron, and thyroxine, 0.01 micron, alone or in combination, did not change DNA or protein synthesis, or morphology, possibly because of the relatively short (24 hour) time period. Our organ culture system emphasizes the differences between suckling rat ileum and the rest of the intestine, and provides a new tool for evaluating, over a 24-hour period, the developing rat small intestine.


Nutrition labeling statement. The Board of the National Nutrition Consortium.

The National Nutrition Consortium Board commends the FDA for its efforts to provide nutrition information to the consumer. We emphasize the necessity of supporting this system with a comprehensive nutrition education program. The system should lend itself to providing as much information as is possible about the total food supply. Changes in the current system must be based on well-designed and carefully analyzed consumer research data.


Suppression of food intake by adenosine and inosine.

The effect of adenosine and inosine on food consumption was tested by a 4 hr satiety assay in rats fasted overnight who then received injections subcutaneously, and also in ad libitum fed rats infused intravenously for 24 hr periods. It was found that adenosine, and to a lesser degree inosine, produced a significant suppression of food intake (86 and 69% reduction from control, respectively) during the 1st hr after subbcutaneous injection. This effect persisted for 4 hr, at the end of which both substances produced an average 37% reduction in food intake from control values. This effect of adenosine was also found in ad libitum-fed animals infused intravenously with adenosine for 24 hr (35% reduction from control). These studies report a previously undescribed effect of adenosine and add another substance to the list of agents shown to influence food intake regulation. Since adenosine is known to play a local regulatory role on adipose tissue metabolism and is generated and released from adipose tissue, the present findings may indicate an additional role for adenosine in providing a feedback regulatory signal between the adipose organ and the hypothalamic centers of food intake regulation.


Nutritional deprivation in childhood and the body size, activity, and physical work capacity of young boys.

Clinical nutritional status and physical work capacity at submaximal level were assessed in 96 rural Hyderbad boys, 14 to 17 years of age. Data available on the previous nutritional status of these children when they were 5 years of age were used for classifying them into different nutritional grades. Factors responsible for undernutrition childhood continued to operate on later growth. Both height and weight at 5 years correlated well (P less than 0.001) with current height and weight. About 64% (P less than 0.001) of the variation in physical work capacity at a heart rate of 170/min (physical work capacity 170 kpm/min) could be explained by the differences in current body weight; habitual physical activity explained another 10% (P less than 0.001) of the variation. Malnutrition in early childhood continuing into adolescence could be considered to have adversely affected their work capacity by influencing their body weight. However, even severe undernutrition during childhood had no effect on work performance, when expressed in terms of unit weight. But for the same work load, undernourished subjects had to use significantly higher heart rate at moderate work level as compared to their counterparts.


Effects of a vigorous walking program on body composition, and carbohydrate and lipid metabolism of obese young men.

With no attempt made to influence their diet, six sedentary obese men ages 19 to 31 completed 16 weeks of vigorous walking 90 min, 5 days/week, on a treadmill at up to 3.2 mph on a 10% grade, expending about 1100 kcal per session. Body composition studies indicated a loss of 5.9 kg of body fat and a gain of 0.2 kg of lean tissue for a net loss of 5.7 kg. Percentage body fat decreased from 23.3 to 17.4. Monitored food intake initially increased, then progressively decreased below pretraining levels. Work capacity and cardiovascular efficiency improved with training. Plasma cholesterol and triglyceride concentrations were not significantly changed; however, high density lipoprotein cholesterol progressively increased to 15.6% above pretraining levels and the high/low density lipoprotein ratio increased 25.9%. Fasting blood sugar was significantly lower after training. Blood glucose concentrations after a glucose challenge did not significantly change, but a 43% reduction in plasma radioimmunoassay insulin levels and a 36% decrease in the ratio of insulin/glucose concentration occurred. Thus, vigorous regular walking resulted in a reduction of body fate stores, endogenous insulin requirements, and food intake, and perhaps improved the ability to eliminate cholestrol by increasing the plasma high density lipoprotein fraction.


Adipose tissue cellularity in obese nondiabetic men in an urbanized Pacific island (Polynesian) population.

In a Pacific island (Polynesian) population exposed to Westernized food-stuffs and sedentary life during adulthood, the fat cell size in the gluteal region in obese men was 71% higher than in age-matched nonobese controls. Rough estimations of body fat from anthropometric measurements suggest that the obesity of these men were mainly due to fat cell enlargement. Increased blood glucose and plasma lipids were associated with the obesity.


Changes in some lipid variables in obese women during the early days of fasting.

Adult obese human subjects with a normal or slightly disturbed oral glucose tolerance test, were submitted to a 7-day fast. Initial serum triglyceride levels were inversely related to the Intralipid fractional removal rate, reflecting the close dependency of triglyceridemia on clearance efficiency; the correlation was less significant on the 5th day of fasting. The direction of the change in triglycerides during fasting was clearly related to the prefast triglyceride levels, the groups of patients with a lower level showing an increase, the group with a higher level showing a decrease. Changes in triglyceridemia were inversely related to fractional removal rate; changes in lipid clearing from plasma, however, could not explain the direction of changes in triglyceridemia in all subjects investigated. The group of patients responding to fasting with a decrease in triglyceridemia had a lower mean initial serum cholesterol value and their serum cholesterol levels showed a less prolonged increase during fasting than the other groups of patients.


Comparative effects of alfalfa saponins and alfalfa fiber on cholesterol absorption in rats.

Intestinal absorption of cholesterol was measured in control rats fed semipurified diets and in rats fed alfalfa meal, in which saponins had been previously extracted, or this extracted material plus alfalfa saponins. A dose of 2 mg radioactive cholesterol was administered intragastrically, and fecal excretion of labeled neutral steroids measured. Absorption of cholesterol was about 76% in control animals, and about 47% in alfalfa-red rats. Extraction of saponins from alfalfa eliminated the cholesterol absorption-lowering effect, while addition of 0.26% alfalfa saponins to the extracted alfalfa restored its activity. The results demonstrate that alfalfa saponins are responsible for the effect of alfalfa meal in reducing cholesterol absorption, and that alfalfa fiber is not involved in this activity.


Regulation of vitamin B6 metabolism in human red cells.

The effects of pyridoxine and pyridoxal 5-phosphate (PLP) administration on pyridoxine kinase (PnK) and asparate aminotransferase (EGOT), a PLP-dependent enzyme, were studied in human red cells separated into young and old populations by density centrifugation. After a delay of 48 hr, both pyridoxine and PLP increase EGOT activity in mature red cells by activating preformed GOT apoenzyme. In addition, in young erythroid cells, pyridoxine therapy induces synthesis of PnK, while both pyridoxine and PLP induce synthesis of GOT apoprotein. Thus, PLP stimulates EGOT induction without a change in PnK activity, suggesting that PLP enters erythroid precursor cells without prior dephosphorylation. However, with both pyridoxine and PLP, the full induction of enzyme activities reflect the gradual replacement of circulating red cells by newly formed cells with higher enzyme levels. Therefore, the use of EGOT as a measure of vitamin B6 nutritional status requires recognition of the complexities of intracellular enzyme regulation.


The effect of bacterially produced vitamin B12 analogues (cobamides) on the in vitro absorption of cyanocabalamin.

An incubation system containing rat jejunoileum was used to determine whether analogues of cyanocabalamin (CNCbl) inhibited the in vitro absorption of CNCbl. The naturally occurring analogues "pseudo B12,"  "factor A," and the nonnaturally occurring analogue desdemethyl B12, were produced by guided biosynthesis with Propionibacterium arabinosum. Factor B was produced by acid cleavage of cyanocabalamin. Inhibition of Co57-CNBbl uptake was demonstrated for cold CNCbl and for desdemethyl B12, although statistical significance was achieved only for cold CNCbl at 40X and 100X the molar quantity of the radiolabeled CNCbl. However, a trend towards progressive inhibition of specific CNCbl binding was shown as increasing concentrations of CNCbl or desdemethyl B12 were used. No inhibition of specific CNCbl binding could be demonstrated for any of the naturally occurring cobamides tested.


Bile acid metabolism in ascorbic acid-deficient guinea pigs.

Sterol balance techniques have been used to determine the effect of short-term ascorbic acid (AA) deprivation on bile acid excretion in the guinea pig. The effects of a brief (2-week) AA deficiency on bile acid pool sizes and the activity of the rate controlling enzyme in bile acid biosynthesis have been determined. It was found that, while food intake and body weight were not affected by the short-term AA deficiency, liver AA levels had fallen to 25% of control levels. At the same time, the rate of excretion of bile acids and the size of the bile acid pool were both reduced by about 50% in guinea pigs deficient in AA. These results were supported by a decrease in the activity of cholesterol 7 alpha-hydroxylase in the deficient animals. It is concluded that an AA deficiency will significantly impair bile acid metabolism independent of any side effects of clinical scurvy.


The effect of dietary fiber on the postprandial serum vitamin A concentration in man.

In 11 normal female subjects, ages 19 to 22 years, the postprandial serum vitamin A concentration was measured 3, 5, 7, and 9 hr after oral administration 300,000 IU vitamin A-palmitate given with a formula diet to which was added 40 g wheat bran, 40 g microcrystalline cellulose, 15 g apple pectin, 15 g guar flour, 15 g carob bean flour, or 20 g carrageenan. When vitamin A was given together with guar flour and apple pectin 3 hr after starting the experiment, the mean serum vitamin A concentration was significantly higher than in controls. Areas under serum vitamin A concentration curves, taken as a measure of the amount of vitamin A absorbed, were significantly higher when the vitamin was administered together with the investigated dietary fiber substances.


Saliva zinc levels: potential indicators of zinc status.

Mixed saliva was collected from eight adolescent females participating in a metabolic study and from 59 adolescent females participating in a nutrition survey. Zinc concentrations, protein concentrations, and zinc:protein ratios of whole mixed saliva samples and of supernatant samples, which were prepared from the mixed saliva, were determined. Zinc analyses were performed with an atomic absorption spectrophotometer equipped with a graphite furnace. Significantly (P less than 0.05) lower levels of zinc were found in the supernant samples, but not in the whole saliva samples, when the same subjects were fed 11.5 mg zinc daily rather than 14.7 mg zinc daily during the metabolic study. The mean zinc concentrations of the whole saliva and the supernatant samples collected during the survey were 173 +/- 94 (SD) and 30.5 +/- 14.8 ng/ml, respectively. The levels of zinc and protein in the whole mixed saliva (r = 0.460, P less than 0.001) and the supernatant samples (4 = 0.486, P less than 0.001) were correlated. The levels of zinc in both types of saliva samples were not correlated to serum or hair zinc levels of girls in the survey.


Metabolic balances of cadmium, copper, manganese, and zinc in man.

Balance studies of cadmium, copper, manganese, and zine were carried out under constant dietary conditions in eight adult males during two calcium intake levels of 200 and 800 mg/day and in an additional single case during a calcium intake of 1500 mg/day. The dietary content and the excretions of these elements in urine and stool were determined. The mean dietary content of cadmium was 32.9 micrograms/day, of copper 1020 micrograms/day, of manganese 2130 micrograms/day, and of zinc 12.4 mg/day. The ratio of the fecal/urinary cadmium excretion was approximately 1.5 and the main pathway of excretion of the other three elements was via the intestine, while the urinary excretions were very low. The different trace element balances were either slightly negative or in equilibrium, except that the zinc balances was positive in 50% of the cases. All balances should be considered maximal values, as the losses in sweat were not determined. The calcium intake level had little effect on the excretion and retention of these trace elements.


Effect of fiber from fruits and vegetables on metabolic responses of human subjects, II. Calcium, magnesium, iron, and silicon balances.

Intakes and excretions of calcium, magnesium, iron, and silicon were determined for 12 men consuming controlled diets containing fruits and vegetables (high fiber diet) or fruit and vegetable juices (low fiber diet) for periods of 26 days. Magnesium and iron were added to the low fiber diet to make the two diets as equivalent as possible in these respects. Mean daily intakes on the low and high fiber diets, respectively, were: calcium, 1070 and 1166 mg; magnesium, 355 and 322 mg; iron, 21.8 and 26.4 mg; silicon, 21.6 and 45.8 mg. Mean daily balances on the low and high fiber diets repectively, were: calcium +72 and -122 mg; magnesium, +28 and -32 mg; iron, +3.8 and +4.6 mg; silicon, -3.5 and -14.6 mg. Calcium magnesium, and silicon balances were significantly lower on the high than on the low fiber diet (P less than 0.01).


The effect of raw carrot on serum lipids and colon function.

Two hundred grams of raw carrot eaten at breakfast each day for 3 weeks significantly reduced serum cholesterol by 11%, increased fecal bile acid and fat excretion by 50%, and modestly increased stool weight by 25%. This suggests an associated change in bacterial flora or metabolism. The changes in serum cholesterol, fecal bile acids, and fat persisted 3 weeks after stopping treatment.