The proliferative response to epidermis of hairless mice to full thickness wounds. The healing of full thickness surgical wounds from 0 to 14 days has been studied in hairless mice. Within 2 days after wounding the surrounding epidermis is thickened and primarily composed of enlarged basophilic cells. The remnants of the hair follicles attached to the epidermis are converted into cords of enlarged basophilic cells. Epidermal thickening is maximum at 7 days. Associated with the epidermal thickening surrounding the wound edge is an increase in the total number of cells in the stratum granulosum and in the stratum spinosum. The number of basal cells does not change. Mitotic activity and mitotic rate increase within 1 day after wounding. Both reach their peaks by approximately 5 to 7 days and then begin to return to control levels. Mitotic duration does not change.


The effect of chronic hypoxia on the number and nuclear diameter of type I cells in the carotid bodies of rats. We measured the number and nuclear diameter of type I cells in the carotid bodies of 10 normal rats and in 10 rats living in a hypobaric chamber at a pressure of 460 mm Hg for 25 to 96 days. In normal rats, the number of type I rats, the number ranged from 15.92 to 30.77 times 10-3 with a mean of 40.79 times 10-3 which differed significantly from that in the control group. In 5 hypoxic rats the number of type I cells was less than the highest figure in the control group. The mean diameter of the nuclei of type I cells of hypoxic rats (5.5 mu) was greater than that of the controls (5.0 mu). The largest type I nuclei were seen in those rats which had been subjected to hypoxia for the shortest time.


A measurement of attitudes about an activity program. Staff and patient attitudes about an activity program were measured to highlight problems that existed in a paritcular milieu. Statements concerning the rationale for this activity program were compared to determine the similarities and differences between staff and patient perceptions of the program. To create a more therapeutic milieu, suggestions for openness and sharing were made based on the results of the attitude study. Their implementation would require staff and patients to interact on a more nearly equal basis. Such an approach is a bias toward the Maxwell Jones philosophy of therapeutic milieu, the direction in which the ward staff of this study wanted to go. This paper offers a way for the staff to reach their goal and suggests several paths they might take. The attitude questionnaire method used in this study might be a useful tool for those who are studying the therapeutic aspects of ward milieu.


Competition as a motivational incentive. Since motivation is a key concern in rehabilitation, methods of encouraging clients to active participation in therapy are frequently sought. The motivational level of the client is an indicator of the success that can be anticipated in occupational therapy activities. This article identifies the phenomenon of competition as a potential motivator for promoting competent performance by clients receiving occupational therapy services.


Formation of myocardial zonal lesions.

Formation of myocardial zonal lesions. Right ventricular papillary muscles from control cats and from cats subjected to hemorrhagic shock were studied by electron microscopy. Half of the muscles were fixed at the apex of their active length-tension curves following stimulation in a papillary muscle bath. The other half were also fixed under tension. The ultrastructure of each muscle was examined in detail. A series of stages in the formation of myocardial zonal lesions, ranging from minimal changes in the intercalated discs to severe lesions, were identified and interpreted as representing the sequential stages in the formation of zonal lesions. One of the earliest (least severe) changes in the formation of zonal lesions, the separations of actin filaments from the intercalated disc, may be critical to the subsequent development of cardiac failure in hypovolemic shock. Mitochondrial displacement was a late event in the formation of the lesions, occurring only after major alterations had taken place in the sarcomeres and intercalated discs. It was noted that the ultrastructure of mitochondria remained essentially normal, and that there was no cell swelling associated with zonal lesions. This serves as confirmatory evidence that myocardial zonal lesions are a unique form of myocyte injury, are potentially reversible, and are not caused by ischemia.


Pulmonary lymphangiomyomatosis. A review. Anatomic and clinical observations of 28 cases, including 23 previously unpublished, of pulmonary lymphangiomyomatosis are recorded and discussed. This brings the total reported to 57. All patients were women in the reproductive age group with the major complaint of breathlessness. This was usually progressive, and death from pulmonary insufficiency resulted within 10 years. Functional changes were obstructive or restrictive, or both. Pneumothorax, chylous effusions and hemoptysis were frequent complications. Radiographically the lesions initially appear as fine, linear and nodular, predominantly basal densities, and progress to a pattern of bullous change, or honeycombing, involving all portions of the lungs not sparing the region of the costophrenic sinuses as is typical of eosinophilic granuloma. There may be associated pleural effusions. A progressively increasing lung volume is characteristic. The lesions consist of an irregular, nodular or laminar "irrational" proliferation of smooth muscle within all portions of the lung, with loss of parenchyma leading to honeycombing. Proliferated muscle can obstruct bronchioles (with air trapping and formation of bullae often complicated by pneumothorax), venules (with pulmonary hemorrhage and hemosiderosis accompanied clinically by hemoptysis) and lymphatics (with chylothorax or chyloperitoneum). Both thoracic and abdominal lymph nodes and the thoracic duct can also be involved in the myoproliferative process with formation of subsidiary minute channels and obstruction. Renal or perirenal angiomyolipomas can also occur, as exemplified by 2 patients in the present series. Identical pulmonary lesions occasionally occur in tuberous sclerosis. Especially since these patients usually have no neurologic disturbances and are almost women, the possibility of a relationship between tuberous sclerosis and lymphangiomyomatosis must be considered. One feature of note in pulmonary lesions of tuberous sclerosis is the presence of adenomatoid proliferations of epithelium. Such changes were also observed in 2 patients of the present series, and it is remarkable that both of these women had "retarded"children. At present the question of whether by lymphangiomyomatosis is a forme fruste of tuberous sclerosis must be considered as unresolved. It may yield to further investigation, possibility including chromosomal studies.


Unraveling child abuse.

Unraveling child abuse. This paper attempts to clarify the dynamics of child abuse, and to suggest approaches to primary prevention. Child abuse is redefined, within egalitarian value premises, as inflicted gaps in children's circumstances that prevent actualization of inherent potential. Levels of manifestation and causal dimensions of child abuse are identified, and their multiple interactions are traced. Primary prevention is shown to be essentially a political, rather than a purely technical or professional, issue.


Professional abuse of children: Responsibility for the delivery of services. Determination of which children will receive or be excluded from services, as well as the nature and extent of those services is largely the province of professionals. This paper examines the responsibility of professionals and social service agencies for the delivery - and denial-of services to children,discusses children's rights, and examines the role and oligation of professionals in the resolution of larger social issues.


The social construction of child abuse.

The social construction of child abuse. Research on child abuse has traditionally focused on incidence, causes, and prevention and treatment. One facet overlooked is that abuse is social deviance, and is the product of social labeling. Employing the perspective of labeling theory, this paper proposes that causes of abuse are products of social definitions applied by gatekeepers charged with identifying children injured by their caretakers. Gaps in our knowledge of child abuse are pointed out, and suggestions for empirical research are offered.


AOTA Human Resources Project: 3. The member data survey. This article is the third in a series describing the American Occupational Therapy Association's Human Resources Project. The Project consists of several interrelated studies aimed at identifying the supply of occupational therapists and assistants in the United States as of December 1973, and at projecting requirements for their services. The present report is the first of several that will describe the results of the Member Data Survey, the objective of which is to define the geographic, demographic, educational, and employment characteristics of the AOTA membership.


Surrogate mother-child relationships.

Surrogate mother-child relationships. Many children are raised by a surrogate mother after loss of their biological mother. The process of developing a relationship between the child and surrogate is complicated by the image of the biological parent. Interactional difficulties, highlighted by separation and loss, must be worked through to establish a viable bond.


Family reaction to homicide.

Family reaction to homicide. This pilot study identifies a two-phased syndrome experienced by families of homicide victims. The crisis phase consists of an acute grief process, including immediate reactions to the homicide, the funeral details, and police investigations. The long-term reorganization phase includes the psychological issues of bereavement and the socio-legal issues of the criminal justice process.


The assessment of individual coping capacities in a group therapy setting. A modification of the traditional group therapy format is described, in which clinicians responsible for decisions to hospitalize or release are provided a systematic structure for assessing the degree of impairment of patient's abilities to cope with the demands of their human environment.


Mental health mystification and social control. The field of mental health suffers from an abundance of technical jargon. The major social issues that touch upon mental health are debated in these technical terms, but persons most affected by the issues are left out of the debate. Hence, professionals have come to serve as an exclusionary buffer between human anguish and social policy.


Evaluation of methods to improve communication in the physician-patient relationship. Parents of children with congenital heart disease participated in an experiment to assess effects of communication methods on retention, anxiety, and satisfaction in regard to information received from physicans. Restatement of medical information by parents was found to be most effective, especially over time, for retention; results were not significant for anxiety or satisfaction.


Use of mental health services by black students at a predominantly white university: A three-year study. During three academic years, 87 black students were counseled at the mental health clinic of a private western university. Their pattern of clinic use was compared with that of white students, and differences and similarities delineated in presenting problems, symptoms syndromes, and duration and termination of treatment. Knowledge of these problems and patternsmay aid mental health professionals; as well as college counselors and administration in planning adequate support services for minority students.


Emotional responses of women following therapeutic abortion. Factor analysis of post-abortion emotional responses revealed three factors. Negative emotions split into two factors: socially-and internally-based. Positive emotions, constituting the third factor, were experienced most strongly. Correlations with background variables suggest two influences on response: the woman's social environment and her internalized concerns about the abortion.


Mother-child interaction observed at home. Lower-class and middle-class mother-child pairs were observed in their homes. In contrast to other studies, very few class differences were found in maternal behavior. These results are discussed in terms of the contexts in which observations are made.


Interaction patterns in families of autistic, disturbed, and normal children. Six families with autistic children were compared with six families with disturbed children and six with normal children by means of a family interaction task. No differences were found between families with autistic children and those with normal children. Families with disturbed children were found to have less agreement between father and mother than did autistic or normal families.


The ex-mental patient as an employee: An on-the-job evaluation. In light of studies showing negative employer attitudes toward ex-mental patients, a comparative study was made of ex-patient employees and non-disabled employees. Results showed ex-patients indistinguishable from randomly selected employees in job performance, human relations, and overall rating. These findings are discussed in terms of the general employability of the mentally restored. The work project studied is offered as a model.


Meditation and the psychotherapist.

Meditation and the psychotherapist. While meditation derives from religious traditions, it is a behavior accessible to investigation. Recent physiological and behavioral studies are surveyed, and meditation behavior is described. Greater awareness of fellings, enhanced interpersonal perception, and increased present-centeredness are behaviors transferred from meditation, and facilitative both to the psychotherapist and to interpersonal functioning.


The relative body weights of Bornean and Sumatran orangutans. Although original field data suggested that the average Bornean orangutan weighed twice as much as the Sumatran ones, this is shown to be an error. The only statistically significant difference in weight is between males and females, regardless of geographical area or data source.


A study of baboon hemoglobin.

A study of baboon hemoglobin. Electrophoretic analysis of hemoglobin types of 409 baboons of various species, mostly from Senegal, corresponds with the findings of other authors. Baboon hemoglobin is homogeneous as a whole, but differs electrophoretically from that of other monkey species. However, a difference in the electrophoretic mobility of the nonhemoglobin fraction of Papio anubis and Papio cynocephalus suggests a possibly different amino-acid sequence. This information may be useful for the classification in doubtful cases.


Length and weight in rural Guatemalan Ladino children: birth to seven years of age. The present study reports 5,029 length and weight measurements as well as percentile distributions for a mixed longitudinal series of 1,119 rural Guatemalan Ladino children. The study sample, birth through seven years, is representative of children in clinically good health, but of suboptimal nutrition. Boys are longer and heavier than girls over the age range. Guatemalan children of both sexes are smaller than American white children from Denver. Differences are least at birth, and increase through two years of age.  Between two and five years, differences between the rural Guatemalan Ladino and Denver samples are rather stable, but then increase through seven years. Despite these differences there is a linear weight for length relationship which is the same across all preschool ages, both sexes, and for both the Guatemalan and Denver populations. This implies that age, sex, ethnic differences between the two groups compared, and mild-to-moderate protein-calorie malnutrition do not affect the relationship between weight and length in preschool children.


Genetic distance and gene diversity among linguistically different tribes of Mexican Indians. Using gene frequency data for 14 genetic loci, genetic distances between 13 tribes of Mexican Indians belonging to 12 language groups were determined and a dendrogram was constructed. The genetic distance between tribes is correlated more with geographic proximity than with language affinity. The gene diversity (heterozygosity) of the total population was decomposed into the three components, i.e., the gene diversity between three main linguistic groups, the gene diversity between tribes within the main linguistic groups and the gene diversity within tribes. About 95% of the total gene diversity exists within tribes, the intergroup and intertribe components being only about 5%.


Secular trend in body size among college athletes. Height and weight were compared across five birth decades (1850-1899) among 1,121 Harvard athletes who were lettermen in various sports. There were considerable differences in the magnitude of the secular trend among the sport categories (crew, baseball, football, track, ice hockey, and two or more sports). Comparing the 1890-1899 and 1860-1869 birth-cohort samples, football lettermen were 2.6 inches (6.6 cm) taller (p less than 0.001) and 20 pounds (9.1 kg) heavier (p less than 0.001). Crew lettermen were 2.6 inches taller (p less than 0.001) and 8.5 pounds (3.9 kg) heavier (p less than 0.05). For lettermen in other sports, changes in mean height and weight were smaller in magnitude. Differential selection for body size may explain the differences in the magnitude of the secular trend when analyzed by specific sport.


Estimation of race admixture--a new method. The contribution of a parental population in the gene pool of a hybrid population which arose by hybridization with one or more other populations is estimated here at the population level from the probability of gene identity. The dynamics of accumulation of such admixture is studied incorporating the fluctuations due to finite size of the hybrid population. The method is illustrated with data on admixture in Cherokee Indians.


Plasma K plus and insulin: changes during KCl infusion in normal and nephrectomized dogs. Potassium chloride was administered by constant, intravenous infusion in splenectomized, but otherwise normal, dogs. The concentration of potassium, [K+], and of insulin, [insulin], in the arterial plasma was measured at frequent intervals. To assess the relative contributions of extrarenal and renal mechanisms toward the maintenance of normal plasma [K+], the results were compared with data obtained previously in splenectomized, nephrectomized dogs. During the infusion, plasma [K+] increased in the dogs with kidneys intact at a mean rate slightly less than that in the nephrectomized dogs. After the infusion was stopped, plasma [K+] declined to about 0.75 meq/liter above control values in both groups of animals. The results indicate the operation of both renal and extrarenal homoeostatic mechanisms. The renal mechanisms contributed measurably during the infusion of KCl, but not immediately after the infusion was stopped. Simultaneous measurements of plasma [K+] and plasma [insulin] indicate that insulin may be involved in the extrarenal homeostatic response.


Role of angiotensin II in experimental renal hypertension in the rabbit. Hypertension was produced in rabbits by constricting the left renal artery; in nine rabbits the opposite kidney was removed and in eight rabbits the opposite kidney was left intact. To investigate the role of angiotensin II (A-II), 1-sarcosine-8-alanine angiotensin II, a competitive antagonist of A-II, was infused at 6 mug/min per kg body wt for 30 min. In a control group of seven unilaterally nephrectomized rabbits mean arterial pressure averaged 81 mmHg and infusion of the A-II antagonist did not alter the arterial pressure. In a group of Na-depleted rabbits, arterial pressure decreased from 81 to 63 mmHg (P less than 0.01) in response to the A-II analogue. Thirty days after renal artery constriction, seven of the nine one-kidney hypertensive rabbits had normal values for plasma renin activity (PRA) and during infusion of the A-II antagonist arterial pressure was unchanged. However, two rabbits had elevated PRA and the arterial pressure decreased during infusion of the angiotension analogue. In the two-kidney hypertensive rabbits, PRA was normal and arterial pressure was unchanged by infusion of the A-II antagonist. These studies provide evidence that hypertension developed with either a high or normal A-II plasma level in the one-kidney animals; the two-kidney rabbits developed chronic hypertension in which no role for A-II could be demonstrated.


Vascular and adrenocortical responses to a specific antagonist of angiotensin II. Angiotensin II receptors in vascular smooth muscle and adrenal cortex have been characterized in the dog. The evidence was derived chiefly from experiments that assessed the ability of a structural analog of angiotensin II, [Sar1, Ile8] AII, to antagonize the effects of exogenously administered angiotensin II on arterial pressure and aldosterone secretion. [Sar1, Ile8] AII is a potent and specific blocker of the pressor response to angiotensinII; in the adrenal cortex, it is a much less effective inhibitor of aldosterone biosynthesis. These results indicate differences in the receptor sites for angiotensin II in vascular smooth muscle and adrenal cortex. Further, they raise the possibility that angiotensin II stimulates aldosterone secretion by mechanisms other than have already been proposed.


Analysis of the components of bile flow in the rhesus monkey. Bile flow studies were performed in three groups of awake rhesus monkeys. In the first group, the increase in bile flow stimulated by  secretin was not accompanied by an increase in erythritol-14C clearance. Resection of the gastric antrum and small intestine in the second group resulted in stable bile flow at fixed bile salt secretion rates. Linear regression lines for bile flow versus bile salt secretion rate and erythritol-14C clearance versus bile salt secretion rate were parallel, and the Y-axis intercept for the latter was consistently higher than for the former. We concluded that erythritol-14C clearance equals canalicular flow, and ductular reabsorption is constant at all bile salt secretion rates in this species. Bile flow was studied during fasting and feeding, over 6 days, in the third group. A model incorporating four bile flow components was developed and tested by multivariate regression analysis. The data fit the model quite well, explaining greater than 90% of the variation in bile flow. A method of measuring the contribution to bile flow of each of the four components is provided.


Autoregulation of blood flow in the rat kidney. We present evidence showing that renal blood flow (RBF) in the anesthetized nondiuretic rat can be measured reliably and accurately using a noncannulating flow transducer and an electromagnetic flowmeter. In vitro calibration yielded a linear relationship (r=0.998) between flowmeter output voltage and blood flow rates from 0.2 to 10.3 ml/min. Excellent agreement was observed between simultaneous determinations of RBF by the flowmeter and the PAH clearance technique. Glomerular filtration rate and RBF for a kidney with a flow transducer around its renal artery did not differ significantly from corresponding values for the undisturbed contralateral kidney. The relationship of mean RBF with steady-state variations in perfusion pressure was evaluated in 13 nondiuretic rats. RBF averaged 6 ml/min.g kidney wt at arterial pressures (AP) above 100 mmHg. A high degree of autoregulatory efficiency was observed when mean AP varied between 105 and 145 mmHg. Over this pressure range RBF changed only 3% as changes in intrarenal vascular resistance and AP were directly related (r=0.994). Below 95-105 mmHg RBF decreased in a curvilinear fashion with the concavity toward the pressure axis.


Effect of age on transvascular fluid movement. Swellings of the mouse tail and ear were produced by subjecting them to subatmospheric pressures of minus 40 to minus 80 mmHg for 15-60 min. Increase in volume was measured volumetrically in the tail and gravimetrically in the ear. Blood volume increases in the tail, as measured with 51Cr erythrocytes, contributed a minor part of the fluid increase. Comparison of mice from 3 to 36 wk in age showed a large decrease of fluid movement with age, with major changes during the growth period. Study of permeability of the ear under decreased pressure,to intravenously administred Evans blue, showed no influence of age on permeability to the protein-bound dye. Measurement of transmission of the applied negative pressure through the skin, and of compliance of the tissues of the ear and tail in mice of different age groups, indicated that these factors were not responsible for the observed changes with age.


Localized myocardial responses to stimulation of small cardiac branches of the vagus. Direct electrical excitation of small cardiac branches from the thoracic vagus elicited highly localized and differential responses from individualized  segments of the myocardium. For example, small nerves from the vagus at the level of the superior pulmonary veins frequently induced moderate inhibition in contractile force of the ipsilateral atrium with little or no influences elsewhere. Branches from more rostral levels of the thoracic vagus induced changes in atrial contractility, with or without changes in sinoauricular (SA) nodal discharge rates, and often with partial or complete artioventricular (AV) nodal blockade.Excitation of individual, small vagal branches sometimes initiated acceleration in artrial rate and augmentation in atrial contractile force concurrently with complete AV nodal blockade. The negative dromotropic response was eliminated by atropine, leaving only the positive chronotropic and inotropic changes, thus revealing the intermingling of both sympathetic and parasympathetic components even in these small branches. There are frequently in excess of 20 small branches from  the vagal trunk between the level of the caudal cervical ganglion and the superior pulmonary vein on each side which will induce highly selective changes in cardiac function upon stimulation. Inhibitory branches are particularly concentrated in the region of the recurrent laryngeal nerve on either side.


Vasopressin release during nonhypotensive hemorrhage and angiotensin II infusion. These experiments were designed to determine whether angiotensin II (AII) could potentiate the increase in plasma vasopressin (ADH) concentration produced by continuous, nonhypotensive hemorrhage in nephrectomized dogs. Infusion of AII (10 ng/kg.min) into a common carotid artery in nonbled dogs did not increase plasma ADH levels, suggesting that increases in carotid arterial plasma AII concentration alone do not stimulate an increase in ADH release. Subsequently, nephrectomized dogs subjected to nonhypotensive hemorrhage (0.44 ml/kg.min) were infused as follows: 0.9% saline intravenously, AII (10 ng/kg.min) intravenously, or AII (10 ng/kg.min) into the carotid. The Plasma ADH concentration increased in all three groups of dogs during hemorrhage. Although the AII-infused dogs demonstrated significant increases in plasma ADH levels earlier during hemorrhage, these changes were small; there were no statistically significant differences in plasma ADH concentrations among the three groups. These results suggest that increases in plasma AII concentration have little or no significant effect on the volume control of ADH release.


Effect of angiotensin II on renal water excretion. In the present study the effect of angiotensin II (AII) on renal water excretion was evaluated. In dogs undergoing a water diuresis, neither the intravenous (IV) (40ng/kg per min) nor intracarotid (5-10 ng/kg per min) infusion of AII significantly altered urinary osmolality (Uosm) or free-water clearance (CH2O). Intravenous infusion of a competitive inhibitor of AII (1-sarcosine,8-glycine AII) into hydropenic dogs also failed to alter Uosm and CH2O significantly. To examine whether AII might suppress, rather than stimulate, vasopressin release, AII was also infused into hydropenic animals. No effect on Uosm and CH2O was observed during the intracarotid infusion. A significant fall in Uosm and rise in CH2O occurred during the intravenous AII infusion, but reversal after cessation of the infusion was incomplete and statistically not significant. Some suppression of antidiuretic hormone (ADH) release during the intravenous infusion of AII, however, was suggested since no similar alteration in renal water excretion was observed during an intravenous AII infusion in hypophysectomized animals receiving a constant infusion of ADH. Taken together, the present results provide no evidence for a direct effect of AII to alter ADH release or to interfere with the peripheral action of ADH. Suppression of ADH release may sometimes occur with pressor doses of intravenous angiotensin, but this effect is clearly less consistent than previously observed with intravenous norepinephrine.


Ion transport by rabbit jejunum in vivo. Net ion and H2O transport by jejunum adjacent to the ligament of Treitz (proximal jejunum) and midjejunum were measured in vivo by continuous perfusion with HCO3-Ringer solution containing a volume marker. Proximal jejunum secreted Na and H2O, whereas midjejunum absorbed Na and H2O. Both segments secreted CO2 and absorbed K and Cl. D-glucose stimulated absorption of Na and H2O and the transmural electrical potential difference (PD) in both segments, but these changes were not accompanied by alterations in Cl, CO2, or K fluxes. However, the increse in Na absorption caused by 3-O-methylglucose was matched by an increase in Cl absorption. This, in addition to increased tissue lactate concentration after addition of D-glucose, suggests that organic anion maintains electroneutrality for Na transport enhanced by D-glucose. Cholera toxin had no effect on ion transport or PD in proximal jejunum, but cholera toxin stimulated secretion and increased the PD in more distal jejunum. Although proximal jejunum shows spontaneous secretory activity, its capacity for secretion is not as great as more distal small intestine.


Interaction of Ca++ binding sites of troponin: significance for Ca++ movements. Ca++ binding data for seven preparations of troponin and 37 preparations of native tropomyosin were analyzed by the method of nonlinear least squares. The analysis was based on the assumption that two classes of independent binding sites exist. Data from one-third the preparations could not be fitted with all binding parameters at true least-squares minimum, and computed values of parameters for two-thirds the preparations were biologically uniterpretable. We conclude that troponin does not contain two classes of independent binding sites. Comparison of Scratchard plots of Ca++ binding by troponin and native tropomyosin modifies binding through a cooperative effect on troponin. Certain features of the Scratchard plots are imcompatible with the possibility that troponin possess more than two classes of independent sites. We interpret these results to mean that troponin's  binding sites interact and that the interaction is increased by tropomyosin. The interaction would cause Ca++ affinity to vary with time during a muscle contraction. The effect of variable Ca++ affinity on intracellular Ca++ movements and the time course of the active state is discussed.


Right atrium and renal sodium excretion. Inflation of a balloon in the right atrium of 13 dogs resulted in salt and water retention not attributable to changes in GFR, RPF, filtration fraction, mean arterial pressure, left atrial pressure, or renal venous pressure. The response to right atrial balloon inflation was compared with the renal effects  of constriction of the abdominal aorta above the renal arteries and constriction of the ascending aorta. Neither procedure evoked the same response as balloon inflation. Results suggest that the decrease in mean arterial pressure which accompanies balloon inflation accounts for only part of the decreased salt and water excretion. There was no significant difference between the responses of denervated and intact kidneys to right atrial balloon inflation. A binary response to stretching of the right atrium is suggested, both components apparently involving hormonal  mediation.


Comparison of transport mechanisms in isolated ascending and descending rat colon. The mechanisms of water and ion  transport in ascending and descending rat colon were compared using an everted open mucosal sac preparation. Net water flux, measured gravimetrically, was similar in both segments (15.3 plus or minus 1.2 and 13.7 plus or minus 1.3mul h(-1) mg(-1), NS). Net catonic flux J(Na+K),net anionic flux J(Cl-HCO3), and net solute flux Josm were also similar; but the constituents of these flux , namely JNA, JK, and JHCO3, were significantly different. The descending colon absorbed significantly less Na and secreted significantly more HCO3. Only the descending colon absorbed K, whereas net JK across the ascending colon was zero. The PD across either segment ranged from 3 to 7 mV, mucosal side negative. Consideration of net flux and electrochemical gradient indicated that in both segments Na was absorbed actively. The nature of Cl transport could not be ascertained. Assuming transmural movement, HCO3 was secreted (or H ion absorbed) actively. Only the descending colon absorbed K actively. Across the ascending colon K was distributed close to electrochemical equilibrium. The compostion of the absorbates was calculated from Ji/Jv after correction of Jv for filtered water. Both absorbates were equally hypertonic (448.5 plus orminus 9.3 and 421.7 plus or minus 13.2; NS.)The ascending colon absorbate contained a significantly higher Na concentration and no K. The descending colon absorbate contained 15 mM K, about 3 times the K concentration in the bathing solution. It was concluded that the ascending colon and descending colon displayed quantitative differences in Na absorption and HCO3 secretion and a qualitative difference in K transport.


Ferritin and intestinal iron absorption: pancreatic enzymes and free iron. Rat intestinal mucosa gave low yields of ferritin purified by standard procedures. The resulting ferritin had less protein relative to iron and migrated faster electrophoretically than ferritin from other rat tissues. Pancreatic duct ligation reduced these differences, suggesting digestive enzyme attack during ferritin isolation. Even in ligated rats, ferritin accounted for only 5-10% of mucosal iron. However, shortly after giving 59FeCl3 orally, 50% of mucosal radioactivity occurred in cell sap, about equally distributed between ferritin and low-molecular-weight (chelated?) iron. No other cell sap components were 59Fe labeled. Iron may thus be transported as a chelate with which ferritin is in rapid equilibrium. Mucosal ferritin content increased with age and iron treatment and decreased with iron deficiency. The iron-deficient rats showed accelerated 59Fe uptake into blood with little mucosal retention. One day after administering parenteral iron to deficient rats, 59Fe transfer to blood became retarded but 59Fe now accumulated excessively in the mucosa, suggesting that iron status affects transport more rapidly at the serosal than at the mucosal cell surface. A scheme for control of iron absorption is presented.


Enhancement of hypothalamic pressor responses in spontaneously hypertensive rats. The cardiovascular effects of stimulating  the posterior hypothalamus electrically were recorded in awake rats to permit in situ evaluation of central neural mechanisms without previous depression by anesthesia. Weak currents ineffective in normotensive or Doca-hypertensive rats elicited measurable pressor responses in spontaneously hypertensive rats, and when currents above threshold strength were used the responses were always larger in spontaneously hypertensive rats than in others. Reduction in reflex bradycardia probably contributed, at least in part, to the increased pressor responsiveness of spontaneously hypertensive rats to hypothalamic stimulation. Since pressor responses to injected norepinephrine or angiotensin were the same as or less than those in normotensive rats, it was concluded that some mechanism other than enhancement of cardiovascular reactivity is involved. Hypersensitivity of hypothalamic pressor areas was considered an attractive explanation but on the basis of the evidence available a possible hypersensitivity of other sites in the efferent neural pathway cannot be excluded.


Afferent sympathetic nerve fibers with mechanoreceptors in the right heart. Mechanosensitivity of afferent sympathetic nerve fibers from the right heart and the pulmonary artery has been examined. Action potentials of the afferent fibers that responded to tapping the right heart and the pulmonary artery were derived from upper thoracic communicating rami of both sides of anesthetized dogs. The fibers were composed of myelinated Adelta fibers and unmyelinated fibers. The receptive fields of both groups of fibers were located widely in the right heart and the pulmonary artery. Myelinated fibers ceased to fire quickly whereas unmyelinated fibers continued to fire after withdrawl of a brief mechanical stimulus. In the myelinated group, the pressure threshold was 3-50, 6-58, and 3-10 mmHg for right ventricular,  pulmonary and right atrial threshold was 15-58, 22-34, and 4-8 mmHg for right ventricular, pulmonary, and right atrial fibers, respectively. Spontaneous discharge of myelinated fibers was synchronous with each rise and/or fall in intracardiac or pulmonary pressure whereas that of unmyelinated fibers was irregular and independent. A rise in pressure produced by pulmonary embolization or occlusion caused an augumented discharge whereas a fall caused by caval vein occulsion eliminated the discharge. The results indicate the existence of both myelinated and unmyelinated fibers with mechanoreceptors in the right heart and the pulmonary artery.


Puromycin effect on amino acid transport: differential rates of carrier protein turnover. In fetal rat calvaria, puromycin selectively inhibited the uptake of certain groups of amino acids. Puromycin treatment decreased the uptake of glycine, L-proline, and alpha-aminoisobutyric acid but was without effect on the active uptake of all other amino acids tested. In studies of alpha-aminoisobutyric acid uptake, puromycin decreased the maximal transport velocity by 70% but had no effect on the affinity of the transport system for the amino acid. With puromycin treatment, the fall-off in rates of alpha-aminoisobutyric acid uptake was first order with a half-life of 68 min. Insulin treatment increased this half-life to 118 min. These findings suggest that protein components of specific transport systems are degraded at varying rates after puromycin blockade of protein synthesis. Hormones that stimulate amino acid transport (e.g., insulin) may decrease the rate of degradation of these protein components.


Creatinine exchange between mother, fetus, and amniotic fluid. Creatinine exchange between mother, fetus, and amniotic fluid was investigated in rhesus monkeys in  late pregnancy in which a different radioactive-labeled form of creatinine was injected simultaneously into either of two of the three possible compartments. Creatinine specific activity was then determined for each isotope in each compartment over the ensuing 4-6 h. A rapid and extensive bidirectional exchange occurred between all three compartments. Maternal-fetal flux, while bidirectional, seemed to be predominately from mother to fetus. Approximately 35% of labeled creatinine originally injected into the fetus and 25% of labeled creatinine originally injected into the mother were present in the amniotic sac within 2 h. Creatinine pool size was calculated to be approximately 6 mg/kg in both mother and fetus. Comparison of experiments involving living had dead fetuses indicated that the route of creatinine transfer from mother to amniotic fluid was through the living fetus and directly across the chorioamnion in the dead fetus. In addition, the time required for 'mixing' of creatinine injected into the amniotic sac was longer with a dead than with a living fetus but its half-life averaged 4.5 h regardless of fetal status.


Interaction of aortic and carotid sinus baroreceptors: effect of activation times. Changes in pulse-wave velocity were simulated by changing the relative timing between aortic and carotid sinus barorecptor activity in anesthetized rabbits and dogs. In the rabbit, electrical stimulation was used to vary the timing; in the dog, it was also varied by perfusing the carotid sinuses with externally generated pressure pulses that could be triggered in any portion of the cardiac cycle. Changing the relative delay between aortic and carotid sinsus nerve stimulation did not result in variations of blood pressure or heart rate in the rabbit. Varing the time of electrical stimulation of the carotid sinus nerve caused at most 5 mmHg change of blood pressure in the dog. Delay-related heart-rate changes could be usually observed only when the stimulus consisted of short, high-intensity bursts. When the carotid sinus was externally perfused with pulses of pressure, only one out of five dogs showed delay-related variations in blood pressure (3mmHg) and heart rate (6 beats/min). It is concluded that variations in pulse-wave velocity are unlikely to play a significant role in acute cardiovascular control.


Influence of crossbridge compliance on the force-velocity relation of muscle. It is shown that muscle models which describe force generation as being dependent on the extension of the individual crossbridges produce a force-velocity relation of the form: Vf= Visotonic--1/KHS dP/dt. The derivation of this equation is independent of the details of activation and the kinetics of the crossbridges. The velocity, Vf, represents the relative filament velocity, and Visontonic is the relative filament velocity which would maintain a constant muscle force. P. The quantity KHS is the net stiffness of all the force-generating crossbridges in one-half a sarcomere. Experimental methods for determining KHS are suggested . To study the force-velocity relation, computer simulations based on A. F.Huxley's 1957 kinetic model were conducted for isometric and isotonic twitch contractions. The relative filament velocity is found to depend on the contraction mode, exhibiting a sudden increase in an isometric-to-isontonic changeover and a decrease in the reverse process.


Mechanical activity of mammalian heart muscle: variable onset, species differences, and the effect of caffeine. The time course of the ability to shorten during contraction was measured using velocity of shortening of the contractile element corrected for length after quick releases to constant loads, in isolated papillary muscles of the cat, rabbit, dog, and rat. The ratios of time-to-peak shortening ability at preload (TTPA), to time-to-peak active force (TPF), were 0.30, 0.36, 0.32, and 0.70 in the cat, dog, rat and rabbit, respectively. When the pacing rate was increased from 12 to 60/min, peak force was augmented in the cat (36%) and rabbit (108%), while TPF decreased in the cat (by 30%) but not in the rabbit. Various inotropic interventions did not alter the ratio of TTPA/TPF in any species. However, caffeine (10mM) increased this ratio to that normally found in the rabbit, in which it was not altered. Afterloaded force-peak velocity relations of the cat, dog, and rat were curvilinear, but in the rabbit in the control state, and in the cat and dog in the presence of caffeine, these relationships tended to be linear. The differences in the time course of the ability to shorten among these mammalian species may be related to differences in excitation-contraction coupling.


Effect of age and long-term diet on exocrine pancreas of the rat. Effects of age and long-term nutritional treatment on pancreas composition and digestive function were determined in rats fed a cereal-type chow after weaning (experiment 1) or diets with 30% casein and 34% butterfat, 54% starch, or 54% sucrose after 9 mo (experiment 2). The rats were adapted for 1-2 wk to a 15% whole-egg protein diet before killing. In experiment 1, pancreas size, nucleic acid, and digestive enzyme content increased significantly with age up to 3 mo. Values for pancreatic weight and DNA were significantly greater in 28-mo-old rats than in 12-mo-old rats. Pancreatic digestive enzyme content was 65-100% lower in rats with and without gross pathologic lesions. In experiment 2, mortality was higher and pathologic changes were more pronounced by 24 mo in rats fed the butterfat or sucrose diet. Usually, pancreatic enzymes were not reduced as much as in experiment 1, although chymotrypsinogen and trypsinogen concentrations were significantly and negatively correlated with the degree of pathologic change. Apparent digestibility of dietary nitrogen and food energy content was not reduced in rats with reduced enzyme reserves. The rate of incorporation in vitro of label into pancreatic protein and RNA did not differ significantly among aged and control rats.


A three-element model describes excised cat papillary muscle elasticity. The three-element model for skeletal muscle has been widely applied to cardiac muscle. It consists of an active contractile element (CE) that represents the muscle's response to stimulation, in series with an elastic element (SE) and the CE and SE in parallel with another elastic element (PE). There have been problems in interpreting experimental data on muscle elasticity using this model. Data seem to indicate that SE force depends not only on instantaneous length, but also initial length; it is not only elastic. Recent experiments seem to indicate that the SE has time-varying properties; it is not passive. This paper formulates a three-element model in which phi(x) = alpha[e beta(x-x*)-1] governs the elastic elements, where phi = force, alpha, beta = spring constants, x = length, and x* = rest length, which avoids these problems. The SE and PE have the same properties. (Typical values: alpha approximately equals .045 g/mm2, beta approximately equals 5.9 mm-1 for cat papillary at 29 degrees C.). By accounting for the nonlinearity of the SE-PE interaction, this three-element model leads to predictions that agree with published data on excised papillary muscle's elastic properties.


Influence of pituitary growth hormone on DNA synthesis in rat tissues. DNA synthesis was compared in seven tissues of hypophysectomized rats and normally growing controls. Liver, heart, kidney, and three skeletal muscles of hypophysectomized rats incorporated[3H]thymidine into DNA more slowly than tissues of normal rats, measured either in intact rats or upon in vitro incubation of tissue slices. However, removal of the pituitary did not alter incorporation into DNA of brain. Administration of ovine growth hormone to hypophysectomized rats stimulated total body growth and increased incorporation into DNA of diaphragm within 6h. The response of liver to growth hormone was less marked and slower in onset than that of diaphragm. Incubation of diaphragm in vitro with growth hormone, however, did not affect [3H]thymidine incorporation. Hypophysectomy reduced incorporation into nuclear DNA of liver, kidney, and muscle, but did not suppress incorporation into mitochondrial DNA. These results suggest that growth hormone only affects synthesis of nuclear DNA. Autoradiographic studies indicate that DNA synthesis is stimulated in distinct cell types in the different organs, including hepatocytes in liver, epithelia of renal tubules, and fibroblasts within muscle.


Influence of food deprivation and adrenal steroids on DNA synthesis in various mammalian tissues. The DNA content of skeletal muscle increases as young rats grow. Food deprivation prevented this increase: total DNA remained constant, while muscle weight and RNA decreased. Diaphragms isolated from fasted rats incorporated [3H]thymidine into DNA far more slowly than tissues from fed rats. Incorporation returned to control levels on refeeding. Fasting for 24 or 48 h also markedly reduced [3H]thymidine incorporation by slices of liver, kidney, and brain. The factors responsible for this inhibition of DNA synthesis were investigated. Amino acids, insulin, or serum from fed or fasted rats failed to alter thymidine incorporation by muscle. Injection of hydrocortisone into normal rats reduced incorporation into kidneys, liver, and muscle within 4h. Incubation of hemidiaphragms with hydrocortisone suppressed [3H]thymidine incorporation within 2-3h. Adrenalectomy enhanced incorporation into DNA by diaphragm, liver, kidney, and brain. When fasted, adrenalectomized rats showed little or no suppression of [3H]thymidine incorporation and lost less weight than fasted controls. These data suggest that adrenal steroids are important in inhibiting DNA synthesis during normal growth and during fasting.


Transmural coronary venous O2 saturations in normal and isolated hearts. Blood O2 saturations were measured by microscopic oximetry in the small coronary veins of wither open-chest or isolated and blood-perfused dog hearts. Subendocardial saturations (average 34%) were significantly lower than subepicardial (average 52%) in isolated hearts contracting isovolumically at systolic and coronary perfusion pressures of 100 mmHg. Saturations of botb regions fell and were not significantly different from each other (both averaged 16%) with partial coronary occlusion. When MVo2 was increased by calcium infusion, subendocardial saturations fell sharply to about 2% and were significantly, lower than subepicardial (average 10%). Conversely, when MVo2 was decreased by ventricular decompression, saturations rose equally in subendocardium (average 40%) and subepicardium (average 45%) (not significant). These data illustrate the efficacy of cascular autoregulation in isolated hearts. In open-chest dogs, as in isolated hearts with partial coronary occlusion, subendocardial (average 20%) saturations were not significantly diffenent from each other and ranged from 0 to 70%, suggesting the possibility of significant differences either in regional coronary flow or MVo2, or both, in closely adjacent areas throughout the myocardium.


Gluconeogenesis in arctic ground squirrels between periods of hibernation. The hibernation season in the arctic ground squirrel (Citellus undulatus) is broken into 8- to 18- day cycles by short homeothermal periods during which the carboydrate reserves depleted during hibernation are replenished. This study follows a number of metabolities in tissues and body fluids to assess the sources for reconstitution of the glucose reserves: lactate, urea, ammonia, free fatty acid, glycerol, triglyceride, and glucose in plasma; glycogen in liver and muscle; and urea and ammonia nitrogen in urine. Fat is the major energy source during both homeothermal and heterothermal periods, the contribution from glucose being limited to glycolysis. Reconstitution of glycogen is accomplished prior to reentry through maximal use of substrates from all sources including glycolysis, fat, and protein metabolism. Of the new gluconeogenic substrate, one-fourth is supplied from protein and three-fourths from fat.


Effect of hypoxia on vascular responses to the carotid baroreflex. The effect of systemic hypoxia on the vascular responses to the carotid baroreflex was studied in anesthetized, vagotomized, artificially ventilated dogs. One hindlimb, kidney, gracilis muscle, and paw were perfused at constant flow, and neurograms were obtained from renal sympathetic fibers. Bilateral carotid occlusions were performed while the animal was breathing a mixture of air and O2 (mean arterial PO2 = 106 mmHg) and again during ventilation with 10% O2 (PO2 = 40 mmHg). With occlusion, the average increase in mean aortic pressure was 36 mmHg greater during hypoxia than during normoxia and the increase in renal perfusion pressure was 87 mmHg greater; the increase in hindlimb perfusion pressure was identical in both situations. Hypoxia did not change the reflex response of the paw to carotid occlusion and increased that of the muscle vessels by only 10%; the increase in renal sympathetic activity averaged 56 plus or minus 10% more with hypoxia than with normoxia. When the carotid chemoreceptors were destroyed, the greater increase in aortic and renal pressure response to carotid occlusion during hypoxia as compared to normoxia was abolished. Thus systemic hypoxia markedly potentiates the reflex renal constriction caused by the baroreflex, and this effect is due to the carotid chemoreceptor afferent input.


Reflex vascular responses in kidney, ileum, and forelimb to carotid body stimulation. Reflex vascular responses to local carotid chemoreceptor stimulation with hypoxic-hypercapnic, hypoxic, or hypercapnic blood were investigated in pentobarbitalized dogs. Bilaterally isolated carotid chemoreceptors were perfused via an extracorporeal lung circuit. Oxygen and carbon dioxide tensions of blood perfusing the carotid bodies were altered by ventilating the isolated lung with various O2-CO2 mixtures. Ventilation of the whole animal maintained normal systemic O2 and CO2 tensions. Perfusion pressures of the isolated kidney, ileum, forelimb, gracilis and hindpaw were measured during constant-flow perfusion. Carotid chemoreceptor stimulation with hypoxic-hypercapnic blood before vagotomy increased renal vascular resistance but caused no change in intestinal or forelimb resistance. Following vagotomy, hypoxic-hypercapnic, hypoxic, or hypercapnic carotid body stimulation increased renal, intestinal, and forelimb vascular resistance. Forelimb skin and muscle vascular beds contributed about equally to the increase in forelimb resistance. Gracilis muscle and hindpaw resistance also increased during hypoxic-hypercapnic stimulation after vagotomy.


Water and ion transport by the urinary bladder of the teleost Pseudopleuronectes americanus. Water and ion transport by the isolated teleost urinary bladder were studied. The transepithelial electrical PD across sac-type bladder preparations was unstable, i.e., initially mucosa positive but becoming more negative with time. Perfused bladders maintained a low mucosa positive PD which was stable. Both Na and Cl appeared to be actively transported from mucosal side (M) to serosal side (S). Voltage clamping the bladder at 0, -50, or +50 mV had almost no effect on active or passive Na or Cl flux in either direction. Na and Cl transport seemed electrically neutral. Fluid absorption (M to S) was directly correlated with absorption of osmotically active solutes. These solutes were almost all Na and Cl. The bladder acidified and secreted K+ into the mucosal fluid. Divalent ions were concentrated in the mucosal fluid as a result of fluid absorption. Although furosemide and ethacrynic acid inhibited ion and water transport by the bladder, ouabain was effective at a much lower concentration. Ouabain (10(-4) M) inhibited active Na transport when applied only to the mucosal or only to the serosal surface. Ouabain abolished the PD only from the serosal surface.


Differential in vivo pulmonary degradation of prostaglandins E1, B1, and A1. Immunoreactive (IR) plasma prostaglandin (PG) levels were measured in samples collected simultaneously through catheters placed in the right ventricle and the thoracic aorta in fasting anesthetized dogs. There were significantly greater levels of IRPGB (P less than .01) and IRPGA (P less than .05), but significantly less IRPGE (P less than .01) in the aorta than in the ventricle. During femoral vein infusion of PGE1, PGB1, and PGA1, respectively, PGE1 was approximately 87% metabolized, but PGB1 and PGA1 were not degraded by the lung. There was no measurable increase in IRPGB or IRPGA levels in the thoracic aorta during intravenous PGE1 infusion. It was concluded that in the resting state PGE is actively degraded by the lung; that the lung very effectively degrades PGE1 but does not degrade PGB1 or PGA1 during infusion of these prostaglandins; and that pulmonary metabolism of PGE1 probably does not result in formation and release of PGB or PGA into the arterial circulation. Additionally, the possibility exists that in the resting state PGB and/or PGA are actively secreted by the lung, but the immunoassay methodology used does not permit resolution of this point.


Mechanism of NaCl reabsorption by hamster thin ascending limbs of Henle's loop. Two models of ypertonic urine formation in the inner medulla were tested. The active model asserts that thin ascending limbs of Henle's loop (ALH) reasorb NaCl hypertonically by active transport; the passive model suggests the reabsorption is by diffusion down a concentration gradient. Using (Na+) in ascending vasa recta (AVR) as a measure of interstitial (Na+), we found no concentration difference between loop tubular fluid and AVR, when the comparison was made at the bend of the loop, or at an ALH sampling site 1 mm from the bend; the results were the same in antidiuresis and saline diuresis. In saline diuresis with flow of tubular fluid to the ALH slowed by simultaneous collection at the bend of the loop,ALH  (Na+) fell below AVR levels, a result consistent with active transport, but not with a purely passive mechanism. Although contragradient transport was shown only with flow slowed and the corticomedullary gradient reduced, a model suggests the active component contributes almost half the observed Na+ flux in antidiuresis.


Effect of dietary D-penicillamine on metabolism of copper in the rat. When normal rats were put on a diet containing d-penicillamine equivalent to a dosage of about 1.75 g/day in a 70-kg man, there was a prompt, marked decrease in biliary excretion of copper and of radiocopper after its intravenous administration. Urinary copper increased as tissue copper levels decreased; this decrease was most pronounced in bone marrow, kidney, lung, and spleen. Plasma copper increased and p-phenylendiamine oxidase activity increased. Fecal copper decreased modestly, which was probably attributable to decreases in food intake and biliary copper. Copper-toxic rats, already hypercupriuric, excreted more urinary copper when given d-penicillamine.


Effect of glucose on lipolysis and on release of lipolytic products in isolated adipocytes. Isolated adipocytes were prepared from epididymal adipose tissues removed from rats which had been fed or starved for 48 h (fed adipocytes or fasted adipocytes). These cells were incubated at 37 degrees C for 90 min in media containing 0, 3, or 30 mM glucose, with or without norepinephrine (1.0 mug/ml). Then the concentrations of free fatty acids (FFA) and free glycerol (FG) in the total mixture (medium plus cells) and in the medium alone were measured. Addition of glucose to the medium increased the total PG, presumably by increasing the basal lipolysis, and it decreased the intracellular retention ratio of FG (the ratio of intracellular FG to total FG). Addition of glucose did not change the total FFA, but decreased the FFA/FG ratio, presumably by increasing reesterification. The increase in FG and decrease in the FFA/FG ratio on addition of glucose were greater in fed than in fasted adipocytes. The intracellular retention ratio of FFA also decreased on addition of glucose. Glucose enhanced norepinephrine-induced lipolysis (release of free glycerol), and this effect of glucose was greater in fasted adipocytes. However, the increase in FFA in fasted adipocytes induced by norepinephrine was not altered by addition of glucose. In fed adipocytes norepinephrine decreased the total FFA in the presence of glucose. Reesterification of FFA following norepinephrine was increased by addition of glucose. Norepinephrine decreased the intracellular retention ratios of FG and FFA in the presence of glucose. These results suggest that the passage of the lipolytic products, FFA and FG, through the cell membranes may not occur by simple diffusion, but may require energy.


Glomerular-tubular balance for bicarbonate in the dog. Previous work that apparently showed a functional relationship between GFR and maximum bicarbonate reabsorption was done at a time when the effects on the latter of several factors (PCO2, plasma potassium concentration, and extracellular fluid volume expansion) were not recognized. The present study re-examines this relationship, while controlling these factors. In 14 hydropenic dogs, bicarbonate reabsorption per unt GFR increased linearly with increases in plasma bicarbonate concentration. At any level of plasma bicarbonate concentration,the absolute rate of bicarbonate reabsorption was functionally related to the GFR. In six volume-expanded dogs, bicarbonate reabsorption remained stable at 20-22 mmol/liter GFR as plasma bicarbonate was raised to greater than 40mM. The absolute rate of bicarbonate reabsorption increased with large increases in GFR induced by methylprednisolone and high-protein diet. In a third group of dogs, bicarbonate reabsorption varied directly with increases in GFR, while plasma bicarbonate concentration was held relatively constant above the threshold. We conclude there is a close functional relationship between the absolute rate of bicarbonate reabsorption and GFR in individual dogs.


Pressure-flow-diameter relationships in isolated perfused thin limb of Henle. To measure directly the relationships between flow rate, tubule diameter, and flow resistance in thin descending limbs of Henle, isolated tubule segments from the rabbit were studied by in vitro microperfusion. Small increases in pressure and flow cause rapid enlargement of the tubule. Flow resistance is inversely related to tubule diameter and, by its effect on transmural pressure, indirectly limits the extent of tubule dilation. In a range of transmural pressures comparable to that in vivo, the tubule is capable of radial dilations as great as 35% and does not reach its structural limit of distensibility. Flow resistance may be approximately by a Poiseuille equation for cylindrical tubules. The effective luminal diameter is approximately a constant fraction of outer tubule diameter and is defined approximately by the innermost projection of semirigid epithelial nuclei.


Adipose tissue blood flow and cellularity in the growing rabbit. Resting blood flow was measured in isolated, innervated, epigastric fat-pads of 27 male rabbits during growth in the 1st yr of life and found to vary widely in range (7.6-28.1 ml/100 g tissue per min). Definition of adipose tissue composition and of fat-cell size and number made it possible to explain the wide range of flow and to identify two types of relationships between adipose blood flow and tissue constituents. Expressed in the usual manner (ml/100 g tissue per min), adipose blood flow declined with increasing adiposity of the fat depots, and a negative correlation was found between flow and fat-cell volume (r equals -.571, P less than .01). In contrast, when blood flow was expressed on the basis of fat-cell number (ml/108 fat cells/min), a positive and highly significant correlation was found between blood flow per fat cell and fat-cell volume (r equals .842, P less than .001). In the rabbit tissue the relationship of blood flow to fat-cell number and size was more predictable than the usual expression of flow in terms of tissue wet weight. Food deprivation for 18-24 h did not significantly alter these relationships. The results indicate that changes in adipose tissue composition and cellularity, resulting from growth and from accumulation of lipid in enlarging adipocytes, are important determinants of blood flow regulation to adipose tissue.


Whole-brain blood flow and oxygen metabolism in the rat during nitrous oxide anesthesia. The Kety-Schmidt washout technique has been modified to measure whole-brain blood flow and metabolism in the rat. During nitrous oxide anesthesia, 14 rats exhaled (133)Xe, and continuous and simultaneous arterial and cerebral venous samples were drawn from a femoral artery and the transverse sinus of the brain. Extracerebral contamination of the venous sample was minimal, and equilibration of (133)Xe in brain tissue and blood was obtained after 10-24 min of inhalation. Cerebral blood flow was calculated from the total activity of the mechanically integrated arterial and venous samples according to the principle of Scheinberg and Stead. At a mean Paco2 of 40 mmHg, CBF averaged 98 +/- 6 (SEM) ml/100 g-min and CMRO2 averaged 5.4 +/- 0.7 (SEM) ml/100 g-min. CBF changed 2.4% with each millimeter Hg change of Paco2 while CMRO2 changed only insignificantly. The values obtained for CBF are higher than reported for man and large laboratory animals bur reflect the proportionately greater amount of gray matter in the rat brain.


Effects of diuretic states on collecting duct fluid flow resistance in the hamster kidney. Hydrostatic pressures were measured in cortical tubules, long loops of Henle, terminal collecting ducts, and in vasa recta in hamsters. In hydropenia, the loops of Henle and terminal collecting ducts provided the major fluid flow resistances, as judged by the location of hydrostatic pressure drops. In mannitol or saline diuresis, hydrostatic pressures in all tubular segments increased, but pressure drops in loops of Henle disappeared, indicating dilatation of loops. The major pressure drop was in terminal collecting ducts, especially in ducts of Bellini, even though these tubular segments also dilated. At highest urine flows, cortical tubule pressures were higher with the ureter and renal pelvis intact than when they were excised, suggesting laminar flow in the ureter adds a flow resistance at high flows. The pressure drop across the medullary capillary bed was 1-2 mmHg. The summation of medullary capillary hydrostatic and colloid osmotic pressures favored fluid uptake from the interstitium, a relationship enhanced by vasa recta geometry which ensures that descending vasa recta offer 4 times the flow resistance of ascending vessels.


Substrate utilization and oxygen consumption by canine jejunal mucosa in vitro. Oxygen consumption, carbon dioxide production, and substrate utilization by small pieces of canine jejunal mucosa have been measured in vitro. In the absence of added substrate, the Qo2 was 0.21 mumol/h per mg dry wt and the respiratory quotient (RQ) was 0.73 indicating the endogenous substrate to be lipid in nature. When glucose or galactose was added, Qo2 and RQ increased. Metabolism of the endogenous substrate was depressed by fructose but not by glucose or galactose. Less than 15% of the metabolized glucose and fructose was degraded to Co2; 80% of the metabolized glucose was recovered as lactate. Galactose disappeared at one-seventh the rate of glucose, but 40% of that metabolized was degrated to CO2. In all experiments Qo2 showed marked cyclic fluctuations with an amplitude of 30-40% of the mean value and a period of 30-40 min. For tissues from a single animal, the cycles were in phase on a clock time basis, indicating that the cycles were synchronized by some in vivo mechanism.


Neural inhibition of insulin secretion from the isolated canine pancreas. By using an isolated in situ, cross-perfused pancreas preparation, direct neural effects on the immunoreactive insulin secretion rate (ISR) were separated from blood-borne influences. Blood from a large, anesthetized "support" dog was perfused through the pancreas of a small, anesthetized "pancreas" dog. Both splanchnic nerves of the pancreas dog were cut above the diaphragm and stimulated simultaneously (10 Hz, 0.1-ms pulses, 5-15 mA) for three 10-min periods, twice before and once during a pancreatic arterial phentolamine infusion (10 or 20 mug/min). Splanchnic nerve section caused a transient increase whereas stimulation caused a decrease in ISR. Phentolamine infusion blocked this decrease. In control experiments, an epinephrine infusion (25 or 50 mug/kg per min) was made into the systemic circulation of the pancreas dog instead of the first and second neural stimulations. No decrease in ISR occurred. Later neural stimulation (in the absence of phentolamine) was accompanied by a decrease in the ISR in three of four dogs. the ISR can be inhibited by direct neural imput to the pancreas, and this inhibition is mediated by alpha-adrenergic receptors.


Responses to preoptic temperature manipulation in the awake and hibernating marmot. Responses of normothermic and hibernating marmots to manipulations of the preoptic-hypothalamic temperature (TPO) were studied. Independent variables included alteration of TPO and, during normothermia, room temperature. Hibernation occurred at an ambient of 6 degrees C. Dependent variables include brain, subdermal, and surface temperatures, heart rate, and behavioral, electromyographic cortical, and hippocampal responses. Although normothermic autumn marmots displayed most of the usual mammalian responses to alterations of the TPO, evidence of effective dermal vasomotion was not obtained. Single episodes of water drinking accompanied prolonged raising of the TPO; sleep was not elicited. During hibernation, effective central thermoregulation was not apparent until 3 or 4 days had elapsed. After this, thermoregulation was readily demonstrable in response to both raising and lowering the TPO. The apparent open-loop gains (OLG) for rise in body temperature after lowering of the TPO showed an exponential increase in value at lower prestimulus body temperatures. It was postulated that this could be explained on the basis of the recruitment of cold-sensitive neurones, which in turn would provide an explanation for the hypothesized "alarm temperature."


Renal intracortical blood flow during hemorrhage: role of adrenergic mechanisms. Hemorrhagic hypotensin in anesthetized dogs produced a redistribution of renal blood flow from the outer to the inner cortex. The role of adrenergic mechanisms in this redistribution was studied in anesthetized dogs using a radioactive microspheres to determine intrarenal blood flow. Neither renal denervation, nor pretreatment with reserpine altered the characteristic redistribution of renal cortical flow during hemorrhage. These observations suggest that neither intact renal nerves nor circulating catecholamines are necessary for the redistribution of renal intracortical blood flow during hemorrhagic hypotension, and the role of myogenic autoregulation is emphasized.


Cardiovascular function in nonarteriosclerotic versus arteriosclerotic rats. Cardiovascular function of arteriosclerotic (breeders) and nonarteriosclerotic (virgins) male am exercise was examined in the denervated gracilis muscle of the anesthetized dog. The data show that 1) on initiation of heavy exercise, the effluent blood PO2 and pH fall markedly and then rise slowly but remain depressed relative to control during 60 min of exercise hyperemia, while the initial increases in [K+] and osmolality rapidly approach and eventually reach preexercise levels. 2) The enhanced vasodilator activity of venous blood from exercising muscle is attenuated when effluent blood PO2 or pH is corrected to preexercise levels; it is completely abolished when both are corrected. 3) Induced reduction of PO2 or pH in the arterial inflow, and thus venous outflow, of resting muscle produces a fall in resistance; simultaneous reductions of both to levels seen in heavy exercise produce a fally in resistance to near that observed during exercise. Since the enhanced vasodilator activity of venous blood from the contracting muscle was abolished by simultaneous correction of the PO2 and pH, it seems likely that these factors, acting directly or indirectly, are the prinicipal chemicals responsible for the maintenance of the vasodilation seen in canine skeletal muscle during heavy exercise.


Leukocytic pyrogen and sodium acetylsalicylate on hypothalamic neurons in the cat. Leukocytic pyrogen and sodium acetylsalicyclate (NaASA) were microinjected into the preoptic/anterior hypothalamic (PO/AH) area of cats to examine the direct effects of these agents on identified thermoregulatory neurons. The pyrogen and NaASA were administered under thermoneutral conditions to preparations that displayed peripheral or peripheral and central thermoreceptor input. The majority of neurons studied with proximate injection of pyrogen responded in a manner consistent with the set-point hypothesis; i.e., units responding to heating with increased activity were depressed and those showing a decreased discharge with the heat test were excited by the pyretic agent. Injection of NaASA without pyrogen pretreatment caused no significant modification of thermoregulatory neuron discharge in most cases. However, when NaASA was administered after pyrogen, it uniformly antagonized the pyretic effect causing a return of the discharge to the control rate. It may be concluded that pyrogen and NaASA act directly in the PO/AH area to produce fever and antipyresis, respectively, by appropriately offsetting the activity of thermoregulatory neurons.


High K+ effects on PAH transport and permeabilities in isolated snake renal tubules. Effects of high potassium concentrations on para-aminohippurate (PAH) transport by isolated, perfused snake (Thamnophis spp.) distal-proximal renal tubules were studied. Increasing the potassium concentration in bath from 3 mM TO 10 mM OR 40 MM led to about 50% decrease in net PAH transport from bath to lumen in less than 10 min, but transport still occurred against concentration gradient. Cell water PAH concentration was not significantly depressed in 10 mMpotassium and was nearly double control level in 40 mM potassium. Apparent luminal membrane permeability to PAH, calculated from perfusion studies, averaged about 3.5 x 10(-5) cm sec(-1) in 3 mM potassium, 1.15 x 10(-5) cm sec(-1) in 10 mM potassium, and 0.48 x 10(-5) cm sec(-1) in 40 mM potassium. Apparent peritubular membrane permeability, determined from PAH efflux from tubules with oil-filled lumens averaged about 0.5 x 10(-5) cm sec(-1) in 3 mM potassium, 0.29 x 10(-5) cm sec(-1) in 10 mM potassium, and 0.17 x 10(-5) cm sec(-1) in 40 mM potassium. These data suggest that high potassium concentrations depress transepithelial PAH transport primarily by reducing luminal and peritubular membrane permeabilities. Effect of high potassium on PAH transport was reversed within 20 min after restoration of control potassium concentration.


Interrelationship of chlorothiazide and parathyroid hormone: a micropuncture study. Sodium and calcium are normally reabsorbed in parallel in the renal tubule. Both parathyroid hormone (PTH) and thiazide diuretics may influence this relationship. This study was designed to show whether the dissociation of Na from Ca transport produced by thiazides is dependent upon the presence of PTH. Hydropenic thyroparathyroidectomized (TPTX) dogs were given chlorothiazide alone and together with PTH. Chlorothiazide alone significantly increased fractional excretion of sodium (0.5 +/- 0.3-5.6 +/- 0.3%) and calcium (0.74 +/- 0.18-1.4 +/- 0.24%). However, the Ca/Na excretion ratio fell markedly from 1.57 to 0.24%. Micropuncture revealed this dissociation to occur at the distal tubule. Proximal reabsorption of water, sodium, and calcium were inhibited to an equal extent. However, distal fractional sodium reabsorption fell 10% whereas calcium reabsorption remained unchanged following chlorothiazide administration in TPTX animals. When phosphaturic doses of PTH were administered with chlorothiazide, no significant changes were observed in calcium or sodium reabsorption. It is concluded that PTH plays no role in the dissociation of sodium from calcium reabsorption resulting from acute chlorothiazide administration.


Effects of water load on renal glomerular and tubular function in desert quail. Effects of an acute intravenous water load on glomerular and tubular function were studied in the anesthetized desert quail Lophortyx gambelii. Total-kidney glomerular filtration rate (GFR) and single-nephron glomerular filtration rates (SNGFR) of reptilian-type and mammalian-type nephrons increased by more than 50% compared with the GFR and SNGFRs measured during a control mannitol diuresis. Despite the increase in GFR, urine flow rate was only 56% of that in control mannitol diuresis, free-water clearance (CH2o) remained at 1-2% of GFR, and the animals excreted only about 79% of the water load. More than 99% of the filtered sodium and 93% of the filtered water were reabsorbed during the water load. Possible reasons for the increased GFR and the failure to produce a dilute urine or excrete the water load are discussed.


Stimulated amino acid imbalance and histidine transport in rat brain slices. Histidine concentration in the brain decreases rapidly when rats are fed a low protein diet in which an amino acid imbalance is created by addition of an amino acid mixture devoid of histidine. Competition for histidine transport into the brain was suggested as an explanation for this effect. Therefore, animo acid mixtures simulating composition of plasma from rats fed basal or histidine-imbalanced diets were added to media to evaluate their effects on uptake of histidine by brain slices during a 60-min incubation period. At the concentrations actually found in plasma, the unbalanced mixture decreased histidine uptake significantly more than did the basal mixture. Two distinct inhibition patterns were observed with different groups of amino acids: a linear decrease in histidine uptake with a mixture of the small neutral, hydroxyl, basic, and acidic amino acids, and a hyperbolic decrease with a mixture of large neutral amino acids, and a hyperbolic decrease with a mixture of large neutral amino acids. Inhibition of histidine transport by the complete mixtures reflected these two effects. Plasma patterns and concentrations of competitive amino acids as well as the concentration of histidine appear to be factors involved in decreasing histidine transport into the brain.


Frequency responses of down- and guard-hair receptors in the cat. In the saphenous nerve of the barbiturate-anesthetized cat, single-unit recordings were made while stimulating guard-hair of down-hair receptors with sinusoidal or narrow-band "noise" displacements. From the units' frequency responses it was inferred that a significant contribution to their firing rate is made by stimulus displacement as well as by stimulus velocity. The appellation "velocity detector" for these units is only partially correct. The proposed division of guard-hair units into types G1 and G2 was not supported by the results obtained with the stimulus used in this investigation.


Cerebral metabolism in sheep: a comparative study of the adult, the lamb, and the fetus. The cerebral uptakes of glucose, oxygen, lactate, pyruvate, acetoacetate and beta-hydroxybutyrate were compared in the adult, the fetal, and the newborn sheep. Beginning 1-2 days after surgery, we withdrew samples simultaneously from an artery and from the sagittal sinus for up to 2 wk. At all ages glucose was the only substrate taken up in significant quantity relative to oxygen. The glucose-oxygen quotients were 0.98 less than 1.03 less than 1.08 in adults; 0.92 less than 0.99 less than 1.06 in lambs; 0.92 less than 0.98 less than 1.03 in fetuses. These quotients were not significantly different. There was a significant (P less than .05) arteriovenous difference for lactate in the adult (-0.031 mM), but not in the lamb or fetus. A significant (P less than .05) arteriovenous difference pyruvate was found in the adult (-0.013 mM) and in the fetus (-0.020 mM). The findings of a glucose-oxygen quotient of approximately 1 and the lack of significant lactate production in fetal sheep brain are consistent with the hypothesis that anerobic glycolysis is unimportant to the steady-state cerebral metabolism of the fetal sheep.


Microelectrophoresis of PGE1 onto single units in the rabbit hypothalamus. Prostaglandin E1 (PGE1) when micro-injected into the preoptic anterior hypothalamus (PO/AH) of conscious rabbits is a potent pyrogenic agent. We have investigated the action of PGE1 on the activity of single units of the PO/AH area using the microelectrophoretic technique. One hundred and thirty-eight PO/AH units were tested both for their response to changes in local PO/AH temperature and for their response to PGE1 application. Less than 9.0% of the total population of units tested showed any response to PGE1 application. When present, the response was invariably one of mild facilitation. No specific unit type (thermally sensitive or insensitive) appeared to be selectively affected by PGE1. Thus, the proportion of units affected by PGE1 was constant at 8-10% for warm-sensitive, cold-sensitive, or thermally insensitive units. There was no evidence to support an antagonistic role for PGE1 on the effects on norepinephrine on PO/AH units. On the basis of these results, we cannot predicate any simple neuronal basis for the action of PGE1 in producing fever in conscious rabbits. However, it is suggested that the action of PGE1 might be the modulation of presynaptic release of neurotransmitter onto the units of the PO/AH area.


Monosodium glutamate metabolism in the neonatal monkey. Monosodium glutamate (MSG) administered by gastric tube to 10 infant monkeys at doses of 1-4 g/kg produced rapid increases in plasma glutamate (17- to 33-fold) and aspartate (50- to 90-fold) levels. The degree of elevation was proportional to the dose administered. Levels of other amino acids were unaffected. Two of the monkeys exhibited high fasting glutamate levels and abnormal glutamate tolerance curves. Despite this apparent decreased ability to metabolize glutamate, neither these animals nor any of the others for whom morphologic studies have been previously reported demonstrated neurotoxicity. Studies using 14-C-labeled glutamated indicated conversion of administered glutamate to two ninhydrin-negative compounds identified as glucose and lactate, as well as to asparate.


Effects of dehydration on body-water distribution in desert kangaroos. The effect of dehydration on the distribution of water in the bodies of two species of desert kangaroos, the red kangaroo Megaleia rufa and the euro Macropus robustus, has been examined. The volumes of various body-fluid compartments were determined in normally hydrated animals and then after the kangaroos had been dehydrated until body weight declined to 80% of the initial weight. The fluid compartments examined were total body water, plasma volume, intracellular volume (cellular and gut water), and extracellular volume. Both species were camel-like in their response to dehydration in that plasma volume was maintained in both species, falling by only 8.3% in red kangaroos and 7.4% in euros. The pattern of water loss from other compartments differed between species, particularly gut water loss. This compartment, which includes the large rumenlike fore stomach, contributed 56% of the total water loss of red kangaroos but only 22% of the loss from euros. The ecological implications of the preferential maintenance of gut water by the sedentary, cave-dwelling euros have been discussed.


Effect of epinephrine on automaticity of the canine atrioventricular node. Effects of epinephrine on the automaticity of canine AV nodal fibers were studied on spontaneously beating AV node-His bundle preparations. Transmembrane potentials of single fibers of the AV node or His bundle were recorded with microelectrode techniques. Action potentials of most AV nodal fibers were characterized by steep phase-4 depolarization and smooth transition from phases 4 to 0. Epinephrine (0.1-0.2 mug/ml) increased the spontaneous rate of the AV nodal fibers. The slope of phase 4 depolarization was increased and the threshold shifted to a more negative level. These changes probably accounted for the increase in the automaticity of the node. Also, in the presence of epinephrine, the pacemaker of the preparation was consistently located at the AV node had a higher degree of automaticity than the His bundle. The findings of the present experiment, therefore, further support the view that the AV node is automatic.


Prolonged vasodilation following fatiguing exercise of dog skeletal muscle. Prolonged vasodilation follows 20- and 60-min periods of stimulation (4 twitches/s) of dog skeletal muscle with blood flow held constant at 23 plus or minus 2 ml/100 g per min. During stimulation isometric tension development fell 61 plus or minus 3%, and we have operationally defined this as fatiguing exercise. During stimulation vasodilation was maximum. Following stimulation vascular resistance returned to control with average half-times of 6.9 plus or minus 0.6 and 5.8 plus or minus 0.4 min after 20 and 60 min of stimulation, respectively. This prolonged vascular recovery following fatiguing exercise is an order of magnitude slower than vascular recovery following less severe exercise. The pressor response to an intra-arterial bolus of angiotensin (0.5 mug) is not depressed during prolonged vasodilation. Prolonged vasodilation does not appear to be closely linked to changes in tissue oxygen consumption. In addition, the changes in resistance can be dissociated from changes in K+, osmolality, and lactate production following fatiguing exercise. We conclude that prolonged vasodilation following fatiguing exercise is caused by a metabolic vasodilator substance which is yet to be identified.


Use of diphenylhydantoin and diazoxide to investigate insulin secretory mechanisms. In the isolated, perfused rat pancreas, we contrasted effects of diphenylhydantoin (DPH) and diazoxide on glucose-induced biphasic insulin secretion. Either drug partially inhibited the first phase. However, DPH completely inhibited the second phase, whereas diazoxide produced inhibition, then escape and post-inhibitory overshoot. Exposure to DPH prior to glucose further inhibited the first phase, and increasing the dose had no additional effects, whereas only raising the diazoxide dose intensified inhibition of early release. DPH sequentially suppressed early response to a series of two, short, glucose pulses. In contrast, no additional effects of diazoxide were noted after its initial inhibition of the first pulse. A computer analysis was programmed from hypotheses based on these experiments. It suggests that DPH inhibits release from a labile compartment and provision of insulin to that compartment, whereas diazoxide divides the labile compartment into two sequential subcompartments. Further, the computer analysis indicates that, with diazoxide, insulin (or substances on which secretion depends) accumulates not at the final release step but at a proximal portion of the labile compartment.


Effect of cyanide on renal metabolic rate and glomerulotubular balance. Measurements of anesthetized dogs by the heat-accumulation technique showed that cyanide reduced equally the metabolic rates of outer medulla and cortex, whereas combined infusion of ethacrynic acid and chlorothiazide reduced mainly the metabolic rate of the outer medulla. During ethacrynic acid and chlorothiazide infusion, cyanide reduced the remaining sodium reabsorption by an average of 19% and the remaining cortical metabolic rate by 43%, but had no additional effect on the outer medullary metabolism. Metabolic rates remained essentially constant when glomerular filtration rate (GFR) was raised during cyanide infusion from 63 plus or minus 3 to 135 plus or minus 7% of control by carotid constriction or intravenous infusion of angiotensin. Glomerulotubular balance, defined as proportional relationship between sodium reabsorption and GFR during infusion of ethacrynic acid and chlorothiazide, was present only at GFR less than 80% of control in experiments with and without cyanide infusion. We conclude that cyanide inhibits proximal energy-requiring sodium transport which cannot be inhibited by ethacrynic acid and chlorothiazide, but does not alter the range of GFR over which glomerulotubular balance applies.


Renal neuroadrenergic transmission.

Renal neuroadrenergic transmission. To study the role of the renal sympathetic nerves in the regulation of sodium excretion, we examined the renal functional response to left renal nerve stimulation before (group I) and after (group II) left renal adrenergic blockade with guanethidine. In group I dogs, absolute sodium excretion from the left kidney fell markedly after left renal nerve stimulation; the decreases in glomerular filtration rate and renal blood flow were of a similar magnitude. Using the radiolabeled microsphere technique, distribution of renal blood flow to the outer cortex was diminished after left renal nerve stimulation. In group II dogs, guanethidine blocked all of these effects of left renal nerve stimulation. In group iii studies, a low level of left renal nerve stimulation was used which resulted in a decrease in sodium excretion in the absence of changes in glomerular filtration rate, renal blood flow, or intrarenal distribution of blood flow; this effect was blocked by renal adrenergic blockade with guanethidine in group iv studies. These data support a role for the renal sympathetic nerves to directly influence renal tubular sodium transport in the absence of alterations in renal hemodynamics.


Quantitative relationship of renal glucose and sodium reabsorption during ECF expansion. To investigate the quantitative relationship between glucose and sodium reabsorption during extracellular fluid (ECF) expansion and to examine the possible contribution to glucosuria of passive diffusion of glucose from peritubular blood to tubular fluid, renal clearance studies were carried out in dogs. It was found that ECF expansion with isotonic saline or Ringer solution causes a decrease in the maximal rate of glucose reabsorption (TmGlc), which is inversely and linearly related to fractional sodium excretion (FENa) over a range from less than 1% more than 25% FENa (r equals -0.394, P less than 0.001). A continuous relationship between TmGlc and FENa could be demonstrated as the ECF was expanded in individual animals as well as in pooled data. Infusion of albumin solution to preferentially expand the plasma volume and decrease proximal tubular sodium reabsorption produced a 24% fall in TmGlc suggesting that the proximal tubule is the site of interrelated glucose and sodium reabsorption. After pulse injections into the renal artery, [14-C]glucose and insulin had the same appearance time in the urine, thus failing to demonstrate diffusion of glucose from blood into the tubule in saline-loaded dogs as well as in dogs in normal sodium balance. It is suggested that ECF expansion exerts its effect on glucose reabsorption by inhibiting the coupled transport of glucose and sodium across the epithelium of the renal proximal tubule.


Studies of the electrical potential difference in rat proximal tubule. The electrical potential difference (PD) in the rat proximal convoluted tubule was investigated in vivo as a function of distance from the glomerulus. The PD was found to be invariably negative (up to -4.5 mV) in the earliest segments (less than 0.5 mm from the glomerulus) and rose to positive values (+2 to +4) in the later segments (1 mm beyond the glomerulus). This change in PD correlated with the bubule fluid-to-plasma (TF/P) chloride ratios, which rose from unity in the early segments to approximately 1.3 in the late. Corresponding changes in PD and chloride ratios could be elicited by single-nephron stop-flow techniques in the early segments. Luminal perfusion techniques demonstrated a direct relationship between PD and tubule fluid chloride concentration. Acetazolamide was found to significantly reduce both late proximal PD (less than +2 mV) and TF/P chloride ratios (less than 1.06). Split-drop studies demonstrated that the negative PD in the early proximal tubule was dependent on the presence of glucose and alanine and the absence of a chloride gradient, whereas in the late proximal tubule under the same conditions the PD was not significantly different from zero. In this segment of the nephron the positive PD in free flow appeared to result from the chloride diffusion potential generated by preferential HCO3 reabsorption. These results provide further demonstration of intrinsic differences in the transport properties along the length of the proximal convoluted tubule.


Suppressive action of prolactin on renal response to volume expansion. The effects of prolactin on rat renal sodium and water handling during volume expansion were studied using clearance techniques. Both control and experimental adult male Wistar rats were prehydrated with an oral water load of volume equal to 2.5% body weight (BW). At least 3 h later, a continuous intravenous infusion of ovine prolactin (NIH-P-S8), 7.1 mug/h per 100 g, was started in the experimental group. After a 1-h steady-state period, the rats were given an intravenous expansion infusion of either hypotonic saline (2.5% BW), isotonic saline (2.5% and 7.5% BW), or blood (2.5% BW). In all control hypotonic and isotonic saline-expanded animals, within 1 h the rats excreted a volume of urine equal to over 50% of the volume of saline infused. The diuretic and natriuretic responses to saline expansion of prolactin-treated rats were significantly smaller than controls. In contrast to the effects of prolactin on the renal response to saline infusions, it did not alter the natriuretic or diuretic response to blood infusion. Prolactin may be counteracting the effects of physical factors on the regulation of sodium reabsorption in the proximal tubule.


Renal secretion of [35-S]furosemide and depression by albumin binding. It was determined by use of [35-S]furosemide and an ultrafiltration procedure that furosemide is bound extensively to bovine serum albumin. When 500 muM furosemide and albumin at a concentration of 2.5 g/100 ml were used, approximately 90% of the drug was bound. With this same amount of furosemide, but with 3 times as much albumin, binding was about 98%. Using a 25-fold lower concentration of furosemide, 20 muM, binding was nearly 98% with 2.5 g albumin/100 ml, and was over 98% with 7.5 g albumin/100 ml. These same concentrations of furosemide and albumin were used to investigate the excretory and secretory rates of [35-S]furosemide in the isolated perfused rat kidney. Tubular clearance (i.e., secretion) of [35-S]furosemide was inversely related to the concentration of albumin in the perfusate. In kidneys perfused without albumin, tubular clearance of the drug was 6-20 times that found when 2.5 or 7.5 g albumin/100 ml, respectively, was used. Probenecid, with or without albumin, reduced the clearance of furosemide to that of its filtration rate. It is concluded that at physiological albumin concentrations, a very small fraction of circulating furosemide will be available for filtration, and tubular-fluid and urinary furosemide will arise predominantly from secretion. Because of extensive binding of furosemide to albumin, the renal secretory process itself is depressed, and the rate of secretion will be dependent, in part, on the concentration of unbound drug.


A cognitive model of hallucinations.

A cognitive model of hallucinations. Hallucinations occur in a wide variety of altered states of consciousnes and are an important symptom in various psychiatric syndromes. Several psychological and biological theories of their origin have offered, ranging from the concept of wish fulfillment, to the hypothesis of an electorchemical release of the perceptual system, to denials that hallucinatory phenomena exist. No explanation has completely satisfied clinicans, probably because the word "hallucination" labels a complex set of phenomena. The author accepts this complexity and offers a conceptual analysis of four key dimensions of the halucinatory experience in an attempt to clarify the gamut of experiences that may be called hallucinations.


School phobia and other childhood neuroses: a systematic study of the children and their families. The authors developed reliable clinical rating scales to compare 35 children with school phobia and their families with a matched sample of children with other neuroses and their families. Twice as many school phobic children as children with other neuroses showed excessive separation anxiety, dependency, and depression. Although a mutually hostile-dependent interaction was found in most of the families of children with school phobia, the development of school phobia appeared to be dependent on defects in character development in the children as well. The authors discuss the etiological significance of the almost universal parental pathology and family malfunction for both groups of children.


A study of attitudes toward menarche in white middle-class American adolescent girls. Material from interviews with 35 premenarcheal and postmenarcheal girls suggests that menarche is an emotional event related to the adolescent girl's emerging identity as an adult woman, her newly acquired ability to reproduce, and her changing relationship with her mother. However, our culture tends to ignore the affective importance of menarche and instead conveys the view that it is a hygienic crisis. The authors suggest the need for developing a socially and culturally appropriate substitute to serve the emotional function that more primitive societies have met with social rituals, thus meeting the psychological needs of the young adolescent girl.


A program of research training in psychiatry: ten-year evaluation and follow-up. Nineteen psychiatrists who participated in the research training program at Boston University School of Medicine from July 1962 to June 1972 were surveyed by questionnaire to determine how participation in the training program may have affected their subsequent professional careers. Results indicate that-probably via a happy combination of self-selection, screening, and the actual experience of research training-these 19 psychiatrists constitute an impressive group who are active in research, publish extensively, and assume substantial teaching responsibilities at medical schools. The authors suggest tha a postresidency program in research training can be extremely important to the development of careers in psychiatric research and to a more scientifically grounded profession.