Associative symmetry in the PA learning of retarded and nonrerarded children. Mentally retarded and nonretarded children learned pairs of pictures in a single-function order (A and B terms of each pair were in the same position throughout) or in a double-function order (all items were re-paired and served as A and B terms). Associative symmetry was demonstrated by all groups when the lists were presented single-function; forward asymmetry was demonstrated when the list was presented double-function. When categorized pairs were presented double-function, items that were correctly associated by category produced symmetry; items that were correctly associated but not by category produced forward asymmetry. The possible influence of single vs. multiple associations on associative symmetry was discussed.


Effects of imitation training on immediate and delayed imitation by severely retarded children. Contingent reinforcement was used in training eight severely retarded children who were previously judged to be nonimitative. A yoked control group was given comparable training, but with noncontingent reinforcement. Posttests of imitation of new behavior of a reinforced model showed significant immediate and delayed (15 minutes) imitation only in the contingent-reinforcement group.


Decision time and movement time as a function of response complexity in retarded persons. The decision time (reaction time [RT]) and movement time of retarded persons as a function of the amplitude and precision of a discrete movement in both simple and choice RT paradigms was examined. The results showed that RT for retarded persons was considerably longer and more variable than for nonretarded persons. Movement difficulty only elevated RT with both populations in the choice RT paradigm, and the RT regression coefficient for the retarded subjects was considerably greater than that for the the nonretarded group. Retarded subjects' movement time was significantly slower than that of the nonretarded subjects. Movement difficulty elevated movement time for both populations, as defined by Fitts's (1954) law. The slope of the movement-time regression coefficients was significantly higher for retarded persons and did not change across 5 days of practice. These findings suggest that information-processing differences in motor skills between populations can be attributed to response parameters.


Construct and ecological validity of short-term memory measures in retarded persons. The performance of retarded subjects on five short-term memory tasks was analyzed in order to determine whether these tasks possessed construct and ecological validity. I predicted that certain components of each task required an active strategic process for optimal performance, whereas other components would only require a passive process. A principal axes factor analysis was performed on the intercorrelations of these components, and three factors were isolated that accounted for performance on the five tasks. Two of these factors were viewed as representing active and passive processes, and the third factor was determined by a recognition-memory task and, apparently, did not require the same processes as the recall tasks. These findings indicated that some of the short-term memory tasks possessed construct validity. An additional analysis was the investigation of the ecological validity of the various short-term memory tasks. Several multiple-correlation coefficients between memory scores and measures of adaptive behavior were significant and support the interpretation that the measures of short-term memory are ecologically valid.


Reactivity of self-monitoring procedures with retarded adolescents. The reactivity of self-monitoring procedures with retarded adolescents was investigated using single-case designs. The effects of two variables, social reinforcement and feedback, on the degree of reactivity were also examined. Both subjects monitored a socially undesirable behavior and were asked to self-record for extended periods of time with minimal cues from the environment. The results indicated that self-monitoring produced reactive decreases in the target behavior. Reinforcement had a differential effect across subjects, further altering the target behavior for only one subject. Feedback decreased the behavior for the second subject. The subjects' accuracy in self-recording was quite low.


Social reinforcement and the naturally occurring social responses of severely and profoundly retarded adolescents. This study was designed to determine if the deficits in social behavior of retarded persons might be due, in part, to the failure of their environment to maintain that behavior. Using an ABAB design, we systematically ignored severely and profoundly retarded, institutionalized adolescents and gave them social reinforcement for appropriate social behavior. Social behavior decreased during nonreinforcement conditions and increased during reinforcement conditions. The data suggest that deficits in social behavior of retarded persons may be due to failure of their environment to maintain such behavior. Implications of these findings for staff behavior and the utility of the present procedure for increasing social behavior of institutionalized retarded persons were discussed.


Adaptive behavior and Uzgiris-Hunt Scale performance of young, developmentally disabled children. The relationship between performance on a Piaget-based infant scale and adaptive behavior was assessed for 25 developmentally disabled infants and preschool children. Results indicated a significant relationship between these measures. Canonical analysis suggested the relevance of the Piagetian abilities of object permanence and foresight and the adaptive behavior skills of self-help and social behavior for this relationship. Discussion centered on research implications emerging from these findings.


Facilitation of class-inclusion performance in mildly retarded adolescents: feedback and strategy training. Two experiments were conducted to explore the feasibility of training mildly retarded adolescents to solve class-inclusion problems. In Experiment 1, the effects of training consisting primarily of feedback were investigated. In Experiment 2, training with feedback alone vs. training with feedback plus a counting strategy was compared. Both experiments assessed the generality of training effects to specific training and/or posttest formats. Results suggested that training was generally effective in improving performance with untrained class-inclusion problems on immediate and delayed posttests. Feedback training with pictorial stimuli appeared to be effective regardless of posttest format. The effects of the other training method/format combinations varied according to posttest format.


Comments on "Encoding and high-speed memory scanning..." by Maisto and Jerome. Maisto and Jerome (1977) reported differences in reaction-time (RT) performance between retarded and nonretarded adolescents. They used the additive factor method, and their results showed differences in the speed of active memory scanning between the two populations; however, they violated a critical assumption underlying interpretation of the results, as there was nonindependence of the slope and intercept values of the function relating memory load to RT of retarded subjects. This departure from theoretically acceptable conditions makes the Maisto and Jerome data difficult to interpret.


Comments on the use of the additive factor method with mentally retarded persons: a reply to Silverman. Maisto and Jerome (1977) reported a choice reaction time (RT) study relating the rate of memory scan to level of intellectual functioning. In this study, slope and intercept values of the RT function were found to be inversely related. Silverman (1978) has raised some concern over the conclusions reached by Maisto and Jerome due to the slope-intercept relationship revealed in their study, which seemingly violates one of the underlying assumptions of the additive factor method. Data were presented from previously reported research that places a number of studies with retarded persons as subjects suspect to this violation. Possible explanations for this finding were also provided.


Academic performance and cognitive processes in EMR children. The present study investigated the extent to which simultaneous and successive processing were related both to academic achievement and Verbal and Performance IQs in EMR adolescents. Simultaneous processing involves the integration of individual stimuli into quasi-spatial groups, whereas successive processing integrates individual stimuli into temporally organized successive series. Simultaneous processing was significantly related to WRAT arithmetic and WISC Performance IQ, whereas successive processing was involved in WRAT spelling and WRAT oral reading and negatively related to WISC Performance IQ. Silent reading and WISC Verbal IQ were related to neither processing strategy. These findings were considered in the broader context of the processing demands underlying decoding and comprehension skills in different subject populations.


Autistic children: a study of learning characteristics and programming needs. Learning-acquisition characteristics of six autistic children were studied in order to examine programming needs. Two studies were conducted. Study 1 showed that the first step of a color-cued sequencing task required four times more trials to learn than did the remaining five steps, producing a significant learning-to-learn curve. Study 2 confirmed earlier findings that extra-stimulus prompts are comparatively ineffective with autistic children when compared to within-stimulus prompts and showed extra-stimulus prompting to be effective following the use of within-stimulus prompting on a similar task.


Continuous cervical dilatation monitoring by ultrasonic methods during labor. Continuous recording of cervical dilatation during labor has been investigated in 13 pregnancies. The recordings were obtained with an ultrasonic cervimeter that continuously monitors cervical dilatation from the transit time of ultrasound signals between two piezoelectric crystals attached on the uterine cervix. A small spring-loaded clip allowed each crystal to be fixed on the rim of the cervical os. Clinical accuracy was +/- 0.6 cm. When the ultrasound recording of cervical dilatation is compared to the intrauterine pressure curve, it is characterized by a baseline and wave-shape curve of dilatation (DWP). The maximal amplitude component is called cervical maximal plasticity. The onset of the DWP is related to cervical resistivity, and the end of DWP reflects the relaxation time of cervical dilatation. The data show that as dilatation enters the active phase of labor, the plasticity, the resistivity, and the duration of relaxation of the cervix increase. These observations are discussed and related to the structural changes of the cervix during labor.


The syndromes of hydatidiform mole. II. Morphologic evolution of the complete and partial mole. Hydatidiform moles studied with respect to cytogenetics and morphologic constitution were divisible into two syndromes: (1) complete, classical mole giving a 46 XX karyotype and (2) partial mole with an ascertainable embryo/fetus, dead or alive, giving a triploid karyotype. The complete moles undergo early and total hydatidiform change from edema to central cistern formation, the embryos proper having perished before the establishment of a functioning circulation. Trophoblastic hyperplasia is conspicuous and the connection of this group to chorioncarcinoma is well established. In the partial moles there is a slow hydatidiform change that affects only some of the villi, but which seems to follow along the same lines as in complete moles. There is focal moderate trophoblastic hyperplasia, villous "trophoblastic inclusions" (that appear in triploids only), and maze-like central cisterns in the later cases. The partial mole, 46 XX, partakes of morphologic characteristics of both main syndromes and may represent an unusual syndrome of its own. The two main syndromes can now be distinguished morphologically and the question of the association of the partial mole with chorioncarcinoma has now to be further studied.


Dramatic pyrexic and cardiovascular response to intravaginal prostaglandin E2. The efficacy of prostaglandin E2 (PGE2) for the induction of labor in pregnancies complicated by IUFD or missed abortion has been demonstrated. Gastrointestinal and pyrexic side effects are frequently observed. The following report describes two patients with documented IUFD who experienced a dramatic pyrexic and cardiovascular response to the intravaginal PGE2. In addition, evidence will be provided to account for this unusual pharmacologic reaction, as well as provide a method of managing this unusual side effect.


A study of fetal acceleration tests.

A study of fetal acceleration tests. The fetal acceleration test (FAT) is a means of assessing uteroplacental integrity by observing fetal heart patterns while being stressed by fetal movement. Of 584 tests performed on high-risk obstetric patients, 176 were done within 1 week prior to delivery. Favorable antepartum FAT results correlated with unremarkable initial intrapartum fetal monitor tracings in 128 (97.7 per cent) of 131 cases and also favorable 5 minute Apgar scores (7 to 10) in 128 (97.7 per cent) of 131 cases. An inconclusive FAT correlated with an abnormal OCT or intrapartum monitor tracing in nine of 10 tracings. Two infants with previously abnormal or suspicious FAT, OCT, and intrapartum fetal heart tracings were stillborn. The FAT was also less time-consuming and had fewer complications. These results show the FAT to be an effective clinical test for managing high-risk pregnancies with possible placental insufficiency.


Effects of human maternal venous plasma glucose concentrations on fetal breathing movements. Human fetal breathing movements were studied following the maternal ingestion of either a 50 Gm. oral glucose load or an equal volume of water in 22 healthy women with uncomplicated pregnancies at 32 to 34 weeks' gestation. The percentage of time spent breathing in fetuses of glucose-treated mothers increased from 23.2 +/- 2.2 per cent during the control period to a maximum of 58.9 +/- 5.2 per cent at 105 minutes following the oral glucose load (p less than 0.01) which was one hour following the peak maternal plasma glucose concentration. No similar increase in maternal glucose concentrations or percentage time spent breathing occurred in patients receiving water. Fetal breathing movements were observed in 97 per cent of the 15 minute periods during the second and third hour after maternal ingestion of a 50 Gm. oral glucose load. It was concluded that maternal carbohydrate intake two hours prior to fetal breathing observations should be documented to permit adequate interpretation of fetal breathing activity.


Cardiac output and its distribution and organ blood flow in the fetal lamb during ritodrine administration. The response of the fetal circulation to beta adrenergic stimulation with ritodrine hydrochloride has been investigated by long-term monitoring of the fetal lamb in utero. Ritodrine was infused intravenously either into the ewe or directly into the fetus, and cardiovascular and acid-base responses were measured. Fetal cardiac output and its distribution were measured with the use of radionuclide-labeled microspheres. The output of each ventricle also was measured by means of long-standing implanted electromagnetic flow transducers around the ascending aorta or pulmonary trunk during infusion of ritodrine at various rates into the fetus. Infusion of ritodrine (1.9 mcg. per kilogram per minute) into the ewe caused no change in fetal heart rate, blood pressure, cardiac output, or umbilical blood flow, but did cause an increase in fetal adrenal and myocardial blood flow. Ritodrine infused directly into the fetus produced a marked increase in fetal heart rate and a minimal change in cardiac output. There were no significant changes in fetal or maternal acid-base balance during the ritodrine infusions.


Fetal heart rate reaction to amniocentesis as an indicator of fetal well-being. The reaction of the FHR to amniocentesis in 43 pregnancies is reported. In 10 pregnancies the FHR reacted with deceleration. Eight of the 10 patients underwent subsequent labor and all developed fetal distress requiring cesarean section. In 31 pregnancies the FHR reacted with an acceleration. Twenty-five of these patients subsequently underwent labor without evidencing fetal distress and the remainder were delivered by cesarean section without labor. In two pregnancies no FHR response occurred following amniocentesis. In both no evidence of fetal distress occurred during labor. The significance of this test as an indicator of fetal well-being is discussed.


Labeling of phosphatidylcholine in the alveolar wash of rabbits in utero. Radioactive palmitic acid, choline, and phosphate were given to rabbits 28 and 30 days pregnant and the labeling;of phosphatidylcholine in the fetal lung and alveolar wash was studied. Labeled phosphatidylcholine was detected initially in the alveolar wash three hours after isotope administration. The three-hour delay was independent of precursor studied or gestational age, and the radioactive phosphatidylcholine continued to accumulate in the wash fluid for at least 18 hours. Each labeled precursor of phosphatidylcholine sequentially labeled the phosphatidylcholine from microsomal, lamellar body and alveolar wash lung fractions of the 30 day fetal animals.


Use of partial exchange transfusion preoperatively in patients with sickle cell hemoglobinopathies. Sickle cell anemia and other severe sickle cell disorders (hemoglobin SC and hemoglobin S-thalassemia) are known to complicate surgical procedures in susceptible patients. Although transfusions have been used preoperatively to increase the packed cell volume, we have recently used the method of partial exchange transfusion in the treatment of patients with these disorders in the preoperative period. Forty-two patients with significant sickle cell hemoglobinopathies underwent operative procedures on various surgical services. The goal was to obtain a hemoglobin A percentage of 40 or above in each case, and this required 480 to 1,150 c.c. of buffy coat poor washed red cells (mean 820 c.c.). The number of complications in the intraoperative and postoperative period in this study was compared to those found in the literature. There was a significant decrease in morbidity and mortality rates noted with the use of these transfusions. There appeared to be a great advantage on a cost-benefit ratio, as well as an improvement in the physiologic state of the patient. Although the results of this study show significant improvement over previous investigations, there are many facets unknown concerning the use of this modality under these and other conditions. Therefore, further investigation of this method and restriction of the method of Level III referral centers is advocated until enough patients have been studied to assess the long- and short-term complications of the procedure.


Professional patient-instructors in the teaching of the pelvic examination. A class of 100 second-year medical students was randomly divided into two groups for instruction in the techniques of the gynecologic examination. Each group received a lecture and a demonstration film. The control group then had practical instruction on office or clinic patients. The study group was instructed by specially trained clinical teaching associates who acted both as professional patients and as teachers. After practice in clinics and offices, both groups received a common evaluation by gynecologists and teaching associates. Students who were instructed by clinical teaching associates performed better on subsequent pelvic examinations and demonstrated superior communications skills compared with the control group.


Effect of the specific angiotensin antagonist (Sar1) (Ala8) angiotensin II on blood pressure and the renin-angiotensin system in the conscious pregnant ewe and fetus. A direct relationship was found between maternal diastolic blood pressure and simultaneously measured angiotensin II (All) levels (P less than 0.001) in chronically cannulated pregnant ewes. The infusion of Saralasin to the ewe resulted in a dose-dependent fall in blood pressure (P less than 0.005), the magnitude of which was proportional to the initial All levels (P less than 0.025). Plasma renin and All levels rose significantly during the infusion. No consistent fetal effects were seen. The infusion of normal saline had no effect on blood pressure or hormone levels. Thus it seems likely that the renin-angiotensin system is involved with the maintenance of normal blood pressure in the pregnant sheep. Fetal blood pressure either fell significantly or was unchanged following direct infusion of Saralasin. This may be related to development of the beta-adrenergic nervous system. The renin-angiotensin system may be more important in cardiovascular homeostasis in the immature than in the adult animal.


Sarcoidosis of the female genital tract. Sarcoidosis, a chronic, multisystemic disease, is characterized histologically by discrete, well-formed granulomas with little central necrosis. It can affect any organ system in the body and rarely involves the female genital tract. This report includes the description of a patient with genital involvement by sarcoid granulomas, who presented with postmenopausal bleeding.


The effect of a progesterone-releasing intrauterine contraceptive device on uterine secretion of prostaglandin F2alpha and life-span of corpora lutea in the ewe. Two studies were conducted to investigate the effect of a progesterone-releasing intrauterine contraceptive device (IUD) on uterine secretion of prostaglandin (PG) F2alpha associated with IUD-induced luteolysis in sheep. In bilaterally ovulating ewes receiving an IUD on day 3 (estrus = day 0) intrauterine release of progesterone (90 microgram per day) by the device did not prevent premature luteolysis or the increased concentration of PGF2alpha in uterine venous plasma on day 5 caused by conventional IUD's. In the second study a progesterone-releasing IUD (645 microgram per day) inserted adjacent to the intact ovary at unilateral ovariectomy on day 14 inhibited early luteolysis in the subsequent estrous cycle and reduced the uterine secretion of PGF2alpha on day 5, without affecting concentrations of progesterone in the peripheral circulation at the intervening estrus. It is suggested that locally delivered intrauterine progesterone can inhibit IUD-induced luteolysis in the ewe by suppressing the uterine secretion of PGF2alpha.


A search for antigen-antibody complexes in pre-eclampsia: further evidence against immunologic pathogenesis. Circulating immune (antigen-antibody) complexes have been proposed as possible important in the pathogenesis of pre-eclampsia. Thirty-four serum samples from pre-eclamptic women were examined for the presence of antigen-antibody complexes by the C1q binding and Raji cell assays. Slightly abnormal C1q binding occurred in two serum samples, while all Raji cell determinations were found to be in the normal range for a healthy, nonpregnant population. It is concluded that circulating immune complexes do not occur regularly in pre-eclampsia.


Oxygen flux into the human cornea when covered by a soft contact lens. Corneal thickness was measured in human subjects who wore gel lenses that varied only in center thickness. The amount of corneal swelling that developed was a function of center lens thickness. Based on these data and the results of a previous study, the minimum oxygen tension under the lens necessary to maintain normal corneal hydration was determined to be 10 mm Hg. The critical oxygen flux into the cornea at this oxygen tension is 2 microliter/cm2 x hr. Gel-lens center thickness and oxygen permeability can be altered to increase the oxygen tension at the tear/lens interface and resultant oxygen flux into the cornea by increasing the oxygen transmissibility of the lens.


Measurement of oxygen flux into the cornea by pressing a sensor onto a soft contact lens on the eye. A polarographic oxygen sensor pressed against a soft contact lens worn on the eye gives data from which can be calculated the oxygen flux into the cornea. The procedure requires knowledge of the diffusion coefficient and solubility of oxygen in the contact lens material. The procedure works best when used with contact lenses of about 40% water content.


Age, reading, and myopia.

Age, reading, and myopia. This paper tests whether the use-abuse theory or the biological theory of myopia explains the appearance and progression of myopia among 12--17 year olds in the United States. The use-abuse theory predicts that current amount of reading and cumulative exposure to reading, as indicated by years of schooling, explain myopia. The biological theory predicts that either age from birth or age from puberty explains any tendency for myopia to appear and progress among children or adolescents. Regression analysis shows that education explains all the tendency for myopia to appear and progress among 12--17-years-olds. When we control for education, age is not related to increased myopia. Myopia progresses, on the average, 0.22 D per academic year. However, education explains only a small fraction of the variance in myopia.


The discrepancy between retinoscopic and subjective measurements: Effect of age. Comparison of the retinoscopic and subjective measurements of 1078 eyes of all ages showed that the discrepancy (retinoscopy--subjective) was positive and equal to 0.3--0.4 D in young eyes. The discrepancy diminished with age, eventually becoming negative in the 6th decade of life. The results are explained by postulating that retinoscopic light is reflected from the internal limiting membrane in young eyes and from a layer posterior to the photoreceptors in older eyes.


A new method of determining the primary position of the eye using Listing's law. A new method of determining the primary direction of regard, using Listing's law as a basis, is described. Previous techniques have required a trial-and-error experimental procedure. The present technique requires only a single measurement set of eye torsions in selected gaze directions. Experimental data to illustrate the technique are presented.


Evaluation of the pneuma-tonometer.

Evaluation of the pneuma-tonometer. Intraocular pressure in 125 randomly selected patients visiting the eye clinic at the Massachusetts Institute of Technology for routine care was measured with a Goldmann applanation tonometer and a model 30R Pneuma-Tonometer. Pairs of reading were taken with each instrument when possible, and each trace of the Pneuma-Tonometer measurement was subsequently read blind and independently by two observers. The standard deviation of the differences between the two readers' values obtained on 416 traces was 0.44 mm Hg. The standard deviation of the differences between paired Pneuma-Tonometer readings on 186 eyes was 1.75 mm Hg. With data selected for cause the mean Pneuma-Tonometer reading was 0.40 mm Hg higher, the standard deviation of the differences between the instruments was 1.50 mm Hg, and the correlation coefficient was 0.88. Alternatives to the customary use of linear regression methods of assessing calibration are proposed.


Applying new design principles to the construction of an illiterate E chart. New design principles have been applied to the construction of an illiterate E chart. A chart can thus be produced in which the only variable in the visual acuity task for letters of different size is the letter size itself. A simple method for using this chart in field studies is described.


Morphologic abnormalities in potassium-deficient dogs. Potassium deficiency was produced in 16 dogs by means of a diet containing less than 0.03% potassium. Decreases in serum potassium were first observed after 3 weeks. Morphologic changes occurred only in heart, skeletal muscle, and kidney. Focal myocardial necrosis was observed in 6 of 16 deficient dogs, and skeletal muscle degeneration and necrosis were observed in 14 of 16 deficient dogs. A complex nephropathy consisting primarily of epithelial hypertrophy and hyperplasia in the collecting tubules of the inner stripe of the outer medulla occurred in all the deficient dogs.


A comparison of the hematogenous cell infiltrate evoked by lymphokine injection with that of delayed hypersensitivity reactions. Lymphokine preparations of high potency obtained by in vitro assay were employed in vivo to determine whether they could produce inflammatory responses showing a cellular infiltrate that qualitatively or quantitatively resembled responses of delayed hypersensitivity. Hematogenous cell infiltrates in guinea pig skin were characterized in terms of the number and types of participating cells following intradermal injection of either lymphokines or an antigen (PPD) to which the animals exhibited delayed hypersensitivity. The dose of lymphokine or PPD per skin test site was selected on the basis of comparable ability to enhance vascular permeability. Delayed hypersensitivity responses showed, as expected, a persistent mononuclear cell exudate both in dermis and subcutis, but most notable in the dermis, during the 24 hours following antigen injection. In contrast, the response to lymphokine over the same period was characteristically neutrophilic and principally in the subcutis. There was no pronounced mononuclear cell infiltrate at any time throughout the reaction to lymphokine. It is concluded that preformed lymphokine produces a pattern of increased vascular permeability appropriate to a mediator of delayed hypersensitivity reactions, provided there is sustained secretion of this material. The ability of lymphokine to cause carbon labeling of dermal capillaries is also pertinent to a mediator of delayed hypersensitivity. The absence of significant mononuclear cell accumulation suggests that the in vitro chemotactic activity of lymphokine toward mononuclear cells may be more important for retention of mononuclear cells in the extravascular connective tissue space than for their selective accumulation.


Gentamicin and tobramycin nephrotoxicity. A morphologic and functional comparison in the rat. Fischer 344 rats were treated with tobramycin or gentamicin, 40 mg/kg/day, for up to 10 days or with tobramycin, 120 mg/kg/day, for up to 14 days. Serum creatinine and BUN at the time of sacrifice were determined, and kidney tissues were examined by light and electron microscopy. Rats receiving gentamicin demonstrated progressive renal proximal tubular necrosis which was nearly universal at the end of 10 days. Their BUN and creatinine levels rose progressively over the same period. Even at the higher dosage, tobramycin therapy resulted in only rare foci of proximal tubular necrosis and minimal elevation of BUN and creatinine. Although they occurred later and were substantially less severe, the ultrastructural changes induced by tobramycin were the same as those seen following gentamicin administration. These results indicate that the mechanism of tobramycin-induced renal injury is probably similar to that of gentamicin and that tobramycin is significantly less nephrotoxic in this experimental model.


Macrophages migration through the brain parenchyma to the perivascular space following particle ingestion. Forty-eight rats received intracerebral injections of sterile colloidal carbon. At intervals between 10 minutes and 31 days after carbon injection, the rats were perfused with glutaraldehyde, and autopsies were performed. Between 10 minutes and 3 hours after injection, carbon particles were extracellular and located strictly within the needle track. During the first few days the carbon was ingested by macrophages. Initially absent, carbon-laden macrophages spread to the neuropil immediately surrounding the injection site at 7 to 31 days following injection. These carbon-laden macrophages frequently were elongated within the neuropil and resembled microglia. Carbon-laden macrophages eventually accumulated around local vessels and in perivascular spaces. Many macrophages containing carbon remained in the injection site at the longest sampling interval of 31 days. Results indicate two macrophage responses to colloidal carbon in the central nervous system: a) an indolent population remains in the injection site for at least 1 month and b) a second population of macrophages emigrates through the neuropil. They eventually surround local vessels and enter the perivascular space. The migrating macrophages offer an explanation for the peculiar perivascular cells in Krabbe's disease and may provide a link between the CNS parenchyma and immunocompetent cells.


An ultrastructural study of acinic cell carcinomas of the canine pancreas. Four cases of spontaneous adenocarcinoma of the canine exocrine pancreas were studied by thin section and freeze-fracture electron microscopy. The neoplastic cells in all 4 cases were of acinar origin and showed many alterations of cytoarchitecture compared with normal acinar cells. In the neoplastic cells, zymogen granules varied in number and appearance and contained an abnormal secretory product characterized by 24-nm-thick microtubules. The nuclear volume and surface area and the nuclear cytoplasmic ratio were increased; although the nuclear pore density per nuclear surface area was significantly decreased, there was no change in the nuclear pore density per nuclear volume. There was a decrease in number and size of gap junctions; focal proliferation, fragmentation, and discontinuation of the tight junctions were also noted. The basal lamina (BL) of the neoplastic cells was discontinuous. The tumor microvasculature often appeared as sinusoids and had sparse discontinuous BL. Finally, the endothelium in both tumor and normal tissue contained "tubulo-reticular inclusions" (TRI) which simulated distemper virus and were located in the rough endoplasmic reticulum (RER) and the perinuclear cisternae.


Cytologic responses of postnatal rat lungs to O3 or NO2 exposure. At the level of exposure employed (approximately 14.0 ppm NO2 or 0.85 ppm O3) epithelial cells at the juncture of the terminal airways and proximal alveoli have previously been shown to be seriously injured or destroyed in maturing (35 days of age or older) and adult lungs. Subsequent repair results in the formation of a tissue nodule at this location. In contrast, postnatal rats between birth and weaning have been shown to be highly resistant to the cytotoxic effects of both NO2 and O3. Prior to wearning, exposure to O3 resulted in little or no injury when examined with either the light or electron microscope, and only minor injury and loss of cilia from epithelial cells lining the terminal airways was noted after NO2 exposure. Subsequent to weaning at 20 days of age, however, there was a progressive increase in the cellular response in both the terminal airways and proximal alveoli after exposure to either oxidant gas. A plateau in the response is reached at approximately 35 days of age and continues until the animals are approximately 1 year old. The data are discussed in terms of current theories on endogenous antioxidant mechanisms.


Hemorrhagic toxins from rattlesnake (Crotalus atrox) venom. Pathogenesis of hemorrhage induced by three purified toxins. The pathogenesis of hemorrhage induced by three purified components of rattlesnake (Crotalus atrox) venom was studied at the light and electron microscopic levels. Crude venom was fractionated by anion exchange and gel filtration in four steps. beta-Alanine acetate disk gel electrophoresis was used to demonstrate electrophoretic homogeneity. White mice were injected intramuscularly with 0.1 ml of a sublethal dose of hemorrhagic toxin. Gross examination revealed extensive hemorrhage 5 minutes after the injection of hemorrhagic toxins alpha and episilon; the same amount of hemorrhage was not present until 3 hours after the injection of hemorrhagic toxin beta. Light microscopic examination of muscel after injection of the toxins revealed areas of extensive hemorrhage in which very few intact capillaries could be found and also adjacent areas of slight hemorrhage in which capillaries were in various stages of degeneration. Necrosis of muscle cells was evident in tissue injected with hemorrhagic toxin beta. Electron microscopic examination showed that capillaries from toxin-injected muscle were in various stages of degeneration. Endothelial cells became very thin and broke down into vesicles prior to complete rupture. Gaps were formed within the cells while intercellular junctions remained intact. Plasma and erythrocytes leaked through these gaps and were observed in the endomysium. Many gaps were plugged with platelet aggregations. Collagen and the basal lamina associated with capillaries were usually disorganized or absent. The experimental injection of three purified hemorrhagic toxins induced hemorrhage by the same mechanism as does the crude venom, ie, per rhexis. In addition, one of the toxins, hemorrhagic toxin beta, causes myonecrosis.


Mixed endocrine gastric tumors associated with hypergastrinemia of antral origin. A patient with atrophic gastritis and excessively raised serum gastrin concentrations (4000 to 5000 pg/ml) was found to have multiple polypous tumors of the gastric corpus mucosa. Following gastrectomy, serum gastrin concentrations decreased to undetectable levels. The tumors consisted of a mixed population of endocrine cells. The majority of tumor cells were of the ECL type, but, in addition, enterochromaffin cells of various subtypes as well as agranular cells were found. The tumors were locally invasive and invaded the walls of submucosal blood vessels. The surrounding mucosa showed a severe atrophic gastritis with intestinalization and contained numerous goblet cells, enterochromaffin cells, and cholecystokinin cells. Cholecystokinin cells do not occur in the normal oxyntic mucosa. Hence, the observation of this cell type in intestinalized gastric epithelium suggests that "intestinalization also is associated with changes in endocrine cell populations. Gastrin has been shown to affect the function of the ECL cells. Indications for a trophic action of gastrin on these cells have been obtained. It is discussed whether greatly raised serum gastrin levels in patients with atrophic gastritis may be associated with increased risks for the development of certain types of gastric tumors.


Bipotentiality of response to sex hormones by the prostate of castrated or hypophysectomized dogs. Direct effects of estrogen. Prostatic response to administered estradiol-17beta 17-cyclopentylpropionate (ECP) was studied in castrated or hypophysectomized dogs. Ultrastructural investigation identified two types of epithelial cells, squamous and modified glandular, that resulted from estrogen action. Squamous cells, which predominated, appeared to evolve from basal reserve cells. Estrogen-modified glandular cells have features attributable to estrogen and previous androgen stimulation. Thaw-mount autoradiography of explants located radiolabeled estrogen in prostatic epithelium and stroma of normal and ECP-treated animals, suggesting a role of estrogen in prostatic homeostasis. Epithelium from ECP-treated dogs incorporated 3H-thymidine, indicating that estrogen promotes DNA synthesis in these cells. Greatly enhanced conversion of radiotestosterone to 4-androstene-3,17-dione, with sharply decreased formation of 5alpha-reduced hydroxylation products, and attendant elevation in estradiol-17beta oxidoreductase activity are metabolic markers attributable to the induced squamous and responding stromal cells. The duality of prostatic response to sex hormones is apparent from observations that estrogen stimulates regressed glandular epithelium which had undergone androgen-mediated differentiation before ablation.


Clonal characteristics in layers of human atherosclerotic plaques. A study of the selection hypothesis of monoclonality. Two hypotheses have been proposed to explain the origin of monoclonal cell populations within human atherosclerotic plaques. The first of these proposes a mutational origin: the second suggests that the single clone of cells with the greatest proliferative advantage is selected following repetitive intimal injury. If the selection hypothesis is true, monoclonality should be observed more frequently in the layer of plaque most recently formed. Glucose-6-phosphate dehydrogenase (G-6-PD) isoenzymes were used as cellular markers in aortas of females heterozygous for the A and B isoenzymes. Ten plaques were divided into 45 portions, each of which was subdivided into upper layer, lower layer, and underlying media. No predominance of monoclonality was observed in the upper or lower layers of plaque, with 53% of samples from each layer being monoclonal. In all, 73% of portions of plaque contained at least one monoclonal layer. The layers tended to resemble each other in their clonal characteristics, with 60% of portions having layers with the same clonal characteristics. A significant correlation between isoenzyme distributions in upper and lower layers of the same portion was observed. No consistent trends in isoenzyme distribution in the three layers of each portion were observed. The results are interpreted as providing no evidence for clonal selection as the mechanism by which human atherosclerotic plaques become monoclonal.


Biofeedback training of knee control in the above-knee amputee. Learning to control a prosthetic knee is a difficult task for the above-knee amputee. A biofeedback training system was designed to help with this problem. The system was found to be useful with several aspects of knee control. Fifteen patients completed a biofeedback training program. Two of these patients did not benefit to the same degree as the other thirteen.


Median and ulnar muscle and sensory evoked potentials. The medical literature was reviewed to find suggested clinical applications of the study of the amplitude of evoked muscle action potentials (MAP) and sensory action potentials (SAP). In addition, the literature was reviewed to ascertain the normal amplitude and duration of the evoked MAP and SAP as well as the factors affecting the amplitude: age, sex, temperature, ischemia. The present study determined the normal amplitude and duration of the median and ulnar MAP and SAP in fifty normal subjects. The amplitude of evoked muscle or sensory action potentials depends on multiple factors. Increased skin resistance, capacitance, and impedance at the surface of the recording electrode diminishes the amplitude. Similarly, increased distance from the source of the action potential diminishes its amplitude. Increased interelectrode distance increases the amplitude of the bipolarly recorded sensory action potential until a certain interelectrode distance is exceeded and the diphasic response becomes tri- or tetraphasic. Artifact or poor technique may reduce the potential difference between the recording electrodes or obscure the late positive phase of the action potential and thus diminish the peak to peak amplitude measurement. Intraindividual comparison indicated a marked difference of amplitude in opposite hands. The range of the MAP of the abductor pollicis brevis in one hand was 40.0--100% of the response in the opposite hand. For the abductor digiti minimi, the MAP was 58.5--100% of the response of the opposite hand. The median and ulnar SAP was between 50--100% of the opposite SAP. Consequent to these findings the effect of hand dominance on the amplitude of median and ulnar evoked muscle and sensory action potentials was studied in 41 right handed volunteers. The amplitudes of the median muscle action potential (p less than 0.02) and the median and ulnar sensory action potentials (p less than 0.001) were significantly less in the dominant hand. There was no significant difference between the ulnar muscle action potentials or for the median and ulnar distal motor and sensory latencies in the right and left hands of this group of volunteers.


Electromyographic biofeedback in the reeducation of facial palsy. Electromyographic biofeedback techniques have been successfully applied in various neuromuscular disorders. Data on the use of this technique in reeducation of facial paralysis after initial surgical correction are scarce. The authors have developed a treatment program consisting of EMG biofeedback with the use of the Basmajian-Emory myotrainer. Two case reports are presented which show successful results after a three month training period.


Screening of membrane surface charges by divalent cations: an atomic representation. To arrive at a clear and atomically realistic representation of the process of ionic screening, a model with the following necessary and justifiable constraints was devised. 1) The minimum internuclear distance (IND) between a negative site on the membrane and a cation screening the site is equal to the sum of the site's "equivalent" radius (rs) + the diameter of a water molecule (approximately 2.8 A) + crystal radius of the cation (rc). 2) The average value for the dielectric constant (D) over IND is given by D approximately 80 ((IND - rs - rc)/IND). When this simple atomic model for ionic screening is employed in conjunction with equilibrium ion-selectivity theory, it is possible to predict quantitatively, from coulombic energy calculations, the secondary stereospecific actions of certain alkaline-earth cations as well as the predominant screening effect of these divalent cations at the surfaces of different types of membranes. The model also successfully predicts the transition from a predominantly screening situation to a predominantly binding situation, which was observed experimentally when negative surface charge density was decreased in nerve.


Further similarities of endogenous pyrogen and leukocytic endogenous mediator. The release of endogenous pyrogen (EP) from rabbit peritoneal granulocytes was measured with a three-point log dose-response curve. Release of EP was inhibited when the cells were incubated in media containing potassium or calcium. Measurements of leukocytic endogenous mediator (LEM) activity, i.e., lowering of plasma iron and zinc and increases in blood neutrophils, were made on the same supernatant media. When EP release was inhibited there was a similar inhibition of LEM activity. These results indicate a similarity between the release of pyrogenic and LEM activities. Together with previous purification studies, the results suggest that EP and LEM are similar and may be identical factors.


Calcium and the control of potassium efflux in the sublingual gland. The effects of cholinergic stimulation on K efflux from rat sublingual gland slices was investigated. The sublingual gland slices appeared stable on incubation as indicated by electrolyte content and ultrastructural analysis. Carbachol induced a biphasic increase in release of 86Rb (an index of K efflux); a transient phase lasting 2--4 min was followed by a sustained (or slowly falling) phase. Both phases of the response were blocked by atropine, but only the sustained phase was blocked by omission of Ca or by the addition of LaCl3. The divalent cationophore A-23187 produced a Ca-dependent release of 86Rb. Substance P stimulated a biphasic release of 86Rb, similar to that obtained with carbachol, but epinephrine did not. The response to substance P demonstrated a Ca dependence similar to that of carbachol. When a transient response to carbachol was elicited, no transient response to carbachol was elicited, no transient response to substance P could be obtained. This suggests that the receptors for these agonists may reside in the same cells. Also, the magnitude of the responses suggests that most of the affected cells are probably the mucous elements of the sublingual gland.


A piezoelectric force transducer for single muscle cells. A cantilevered piezoelectric force transducer is described. The cantilevered element has a 6-mm glass extension that can be projected into a horizontal muscle bath from above. By adjusting the length of the piezoelectric bar from 1 to 4 mm, the sensitivity of the device can be varied between 25 and 100 mV/mN (0.25--1.0 mV/mg) with its resonant frequency varying inversely between 8 and 15 kHz. Although moderately fragile, the sensing elements are inexpensive and easily made. The output of the sensing element is amplified by a small, unity-gain, high-input-resistance amplifier mounted on a support block with the element. Although the arrangement does not provide a DC output, its time constant of over 500 s is sufficiently long for measuring tension during muscle contractions lasting 1--2 s.


Effect of somatostatin on myoelectrical activity of small bowel. Somatostatin, a growth hormone-release inhibiting hormone, has been found to be a powerful inhibitor of gastric and pancreatic secretion as well as of hormone release in the digestive system. This study was undertaken to determine the influence of somatostatin on the myoelectrical activity pattern of the small bowel. Three conscious dogs were prepared with electrodes spaced 25 cm apart along the entire small intestine. Intravenous infusions of somatostatin were administered in various doses (0.6--5.0 microgram/kg.h) while spike activity and slow waves were recorded under fasting conditions, after a meat meal, or during intravenous infusion of gastrin, caerulein, or insulin. Somatostatin at a dose of 0.6 microgram/kg.h almost doubled the frequency of the interdigestive myoelectric complex. Somatostatin in fed dogs caused a dose-dependent decrease of the normal fed spike activity, and at higher doses it induced a pattern like that seen in fasting animals. The slow-wave frequency in both fasted and fed conditions was not changed significantly. We conclude that somatostatin given under basal conditions increases the frequency of the interdigestive complex and, when administered after feeding, converts the fed-type pattern to the fasted-type pattern. It may therefore play a promoting role in initiating the interdigestive myoelectric complex.


Splanchnic glucose and muscle glycogen metabolism after glucose feeding during postexercise recovery. Glucose (100 g) was ingested 15 min after bicycle exercise until exhaustion at a work load corresponding to 70% of maximal uptake (series 1), 14--15 h after an identical exercise period, no food being taken in the interval (series 2), and by nonexercised control subjects. Splanchnic glucose output in the exercised groups rose to values 50--300% greater than in controls, amounting to (over 135 min) 59 +/- 5 g in series 1 and 58 +/- 6 in series 2 compared to 28 +/- 6 in controls. The glycogen concentration of quadriceps muscle in series 1 was 65 +/- 2 mmol glycosyl U/kg wet wt before exercise, 16 +/- 13 at the end of work, and 32 +/- 4 at 135 min after glucose ingestion. In series 2, muscle glycogen concentration was 20 +/- 3 immediately after exercise and rose to 44 +/- 5 over the ensuing 14--15 h in spite of continued fasting. It rose to 56 +/- 3 at 135 min after glucose loading. Repletion of leg muscle glycogen after glucose feeding could account for 50--66% of total splanchnic glucose release. It is concluded that during postexercise recovery, a greater proportion of an oral glucose load escapes hepatic retention, allowing repletion of muscle glycogen to take precedence over hepatic glycogen repletion.


Renal glutamine metabolism in rats fed high-protein diets. The influence of protein intake on acid excretion and renal glutamine metabolism was investigated and compared to the effects of NH4Cl-induced metabolic acidosis. Rats fed a diet containing 55% casein excreted more ammonia, phosphate, sulphate, and chloride than did rats fed a 13% casein diet, but, when they were given an 0.1 M NaHCO3 solution to drink, ammonia excretion was no longer elevated. Renal phosphate-dependent glutaminase and phosphoenolpyruvate carboxykinase activities, ammoniagenesis by isolated mitochondria, and the rate of renal gluconeogenesis were all elevated in the rats fed the high-protein diet but not if these rats also drank the sodium bicarbonate solution. Increased glutaminase and phosphoenolpyruvate carboxykinase activities, mitochondrial ammoniagenesis, and gluconeogenesis were all evident in rats made acidotic with NH4Cl. It is concluded that these metabolic adaptations evident in the kidneys of rats fed the high-protein diet are due to the acidogenic effects of increased protein intake.


Jejunal phosphorylation and dephosphorylation of absorbed pyridoxine.HCl in vitro. The phosphorylation and dephosphorylation of absorbed vitamin was studied in rat jejunal everted sacs during in vitro uptake of [3H]pyridoxine.HCl. Kinetic studies during 4-min incubations demonstrated that phosphorylation was saturable (Km, 13.3 micron; Vmax, 0.906 nmol/4 min/g wet tissue) and was significantly inhibited by both structural and metabolic inhibitors. Longer incubations (30-min) demonstrated similar saturation and inhibition of net phosphorylation. Dephosphorylation of the phosphate esters formed by the phosphorylation step also occurred, as demonstrated by pulse-chase experiments. Disappearance of these phosphates was initially rapid, approximated first order kinetics, and apparently was mediated by a phosphatase. Whereas phosphorylation did not appear to affect initial uptake rates for [3H]pyridoxine.HCl by the jejunum, net phosphorylation after more prolonged incubations qualitatively paralleled accumulation of total absorbed vitamin in tissue over the same time. The primary effect of phosphorylation during jejunal uptake of pyridoxine by rat jejunum was to increase the accumulation of absorbed pyridoxine in tissue during prolonged incubations. Dephosphorylation had the net effect of limiting the magnitude of that accumulation.


Diet-induced adipocyte number increase in adult rats: a new model of obesity. Adult rats of various strains became obese when they were fed a highly palatable diet for several months. Analysis of their adipose tissue morphology revealed increases in both adipocyte size and number in most depots. Reintroduction of an ordinary chow diet to such animals precipitated a period of weight loss during which only mean adipocyte size returned to normal. Adipocyte number remained at the elevated level achieved during the period of weight gain. Thus, transient dietary obesity in rats results in a persistent obesity of a purely hyperplastic, nonhypertrophic form. Furthermore, the persistence of the cell number increase suggests that it is the result of proliferation or differentiation rather than of only an increase in the lipid content of a pool of very small and normally undetected adipocytes. An analysis of adipose tissue morphology changes during the course of diet-induced weight gain suggests that the achievement of some specific mean adipocyte size triggers the events that culminate in adipocyte number increase. What mechanisms may link adipocyte size to the formation of new adipocytes remains unknown.


Effect of sequential infusions of glucagon and epinephrine on glucose turnover in the dog. Conscious dogs were infused with 1) glucagon (3 ng/kg.min) alone for 120 min followed by glucagon plus epinephrine (0.1 microgram/kg.min) for 60 min and 2) epinephrine alone (150 min) followed by epinephrine plus glucagon for 90 min. Glucagon alone caused a 10--15 mg/dl rise in plasma glucose and a 45% increase in glucose production that returned to baseline by 75--120 min. After addition of epinephrine, glucose production rose again by 80%. Infusion of epinephrine alone resulted in unchanged plasma glucagon levels, a 60--70 mg/dl rise in plasma glucose, and an 80--100% rise in glucose production that returned to baseline by 60--120 min. When glucagon was added, glucose output promptly rose again by 85%. When glucagon was infused alone, there was a rise in glucose uptake, whereas, with epinephrine, glucose uptake failed to rise and glucose clearance fell by 35--50%. We conclude that 1) hepatic refractoriness to persistent elevations of glucagon or epinephrine is specific for the hormone infused; 2) epinephrine stimulates glucose production in the conscious dog in the absence of a rise in plasma glucagon; 3) the hyperglycemic response to glucagon or epinephrine is determined in part by accompanying changes in glucose utilization.


Fructose-6-phosphate substrate cycling and hormonal regulation of gluconeogenesis in vivo. The possible role of the hepatic fructose-6-phosphate substrate cycle (phosphofructokinase, fructose-1,6-diphosphatase) in the rapid hormonal regulation of gluconeogenesis was investigated in vivo in fasted normal and adrenalectomized rats after administration of [3-3H, U-14C]- or [3-3H, 6-14C]glucose. The plasma glucose 3H/14C ratio was used as an index of substrate cycling because the amount of 3H loss from liver hexose phosphates is determined by the extent of cycling. PFK and FDPase activities limit 3H loss during gluconeogenesis and glycolysis, respectively. Glucagon-stimulated hepatic glucose production is always accompanied by increased substrate cycling, i.e., increased FDPase and PFK activities. The high PFK activity may be a secondary event due possibly to elevated cellular fructose-6-phosphate levels. Decreased substrate cycling, i.e., lowered FDPase activity, always accompanies the depressed hepatic glucose production that occurs during hyperglycemia. Glucagon has no effect on substrate cycling in adrenalectomized rats that are insensitive to the hormone. The in vivo experiments presented provide evidence, although indirect, that glucagon administration results in changes in the fructose-6-phosphate substrate cycle in a living animal. Whether these changes are primary regulatory events or occur secondarily to hormone actions elsewhere is not known.


Electrical and mechanical effects of molecular variants of CCK on antral smooth muscle. Intracellular microelectrode and standard organ bath techniques were used to study in vitro the effects of three molecular forms of the peptide cholecystokinin on the electrical and mechanical activities of canine antral circular muscle. Three forms were studied: the carboxyl-terminal octapeptide of cholecystokinin (CCK-OP), the molecule containing 33 amino acid residues (CCK33), and the peptide termed "cholecystokinin variant" that contains 39 amino acids (CCK39). All three forms increased the force and frequency of spontaneous contractions. They also increased the frequency and the amplitude and duration of the plateau of the gastric action potential. Atropine did not block any of these effects, suggesting that the action of these peptides was largely due to a direct action on the smooth muscle. Complete dose-response curves were determined for the effect of these peptides on the force and frequency of contraction for muscle strips and for the effect on amplitude of the plateau and frequency of the action potential for single cells. CCK39 and CCK-OP had similar potencies and both forms were more potent than CCK33.


Antidiuretic hormone increases renal prostaglandin synthesis in vivo. Studies demonstrating the antagonism by prostaglandins (PGs) of antidiuretic hormone (ADH) action led to the proposal that renal medullary PGs may act to attenuate the physiologic effects of ADH via a negative-feedback loop. Therefore, we examined urinary PG excretion, an indicator of renal PG synthesis, in rats with hereditary diabetes insipidus (DI) utilizing gas chromatography-mass spectrometry. The DI rats, devoid of ADH, excrete much less prostaglandin E2 (PGE2) than normal Long-Evans rats (39 +/- 5 vs. 228 +/- 53 ng/24 h, means +/- SE, P less than 0.005). DI and normal rats were treated for 35 days with ADH while separate groups of DI and normal controls received vehicle only. The ADH treatment increased urinary PGE2 excretion in DI rats to 233 +/- 35 ng/24 h whereas PGE2 excretion was unaffected by vehicle treatment. ADH treatment in normal rats similarly increased PGE2 excretion from 215 +/- 49 to 410 +/- 63 ng/24 h (P less than 0.05). To determine whether the rise in PGE2 excretion is the result of the rise in papillary osmolality, we subjected DI rats to dehydration, which increased urine osmolality from 130 +/- 10 to 302 +/- 12 mosmol/kg H2O but left urinary PGE2 unaffected. We conclude that ADH stimulates renal medullary PGE2 synthesis in vivo.


Ion selectivity and proximal salt reabsorption. Electrophysiological techniques were used in isolated perfused superficial (S) and juxtamedullary (JM) rabbit proximal convoluted tubules (PCT) to examine the relative sodium-to-chloride (PNa/PCl) and bicarbonate-to-chloride (PHCO3/PCl) permeability ratios. We found that the great majority of PCT are sodium selective and that PHCO3/PCl depends on the experimental conditions. In the presence of active sodium transport, PHCO3/PCl is high and increases with PNa/PCl. When PHCO3/PCl is determined after inhibition of active sodium transport or at 25 degrees C, PHCO3/PCl approximates the free solution anion mobility ratio of 0.5 and is independent of PNa/PCl. The difference between PHCO3/PCl determined in the presence of and in the absence of active transport suggests that the lowering of bath bicarbonate concentration in the presence of active transport changes both paracellular and transcellular current flow. In addition, we found that during luminal perfusion with high chloride, low bicarbonate, organic solute-free solutions, the transepithelial electrical potential depends on PNa/PCl and PHCO3/PCl. This potential is approximately 4.0 mV in S PCT with low PNa/PCl and falls progressively to zero in JM PCT with high PNa/PCl. From these data we conclude that anion concentration gradients drive an important diffusive flux of sodium chloride through the paracellular pathway only in PCT with low PNa/PCl ratios.


Extracellular water measurements: organ tracer kinetics of bromide and sucrose in rats and man. Bromide and sucrose distributions were measured as functions of time after tracer injection into 14 rat organs that accounted for 93% of body wt, with the goal of evaluating the use of bromide and sucrose as tracers for the extracellular water volume (ECW). The tracers, Na, 82Br, 125I-labeled human serum albumin, [14C]sucrose, and 3H2O, were used to calculate bromide and sucrose content in red cells, plasma, and 13 blood-free organs. Selective concentration of Br- occurs in RBC, stomach, and skin, accounting in part for the discrepancy between the Br- space and the smaller ECW volume as derived from other methods. Sucrose is rapidly metabolized in the rat and its 14C tracer cannot be used for ECW determination in this species. The kinetics of Br- distribution were estimated in rats and in 16 human subjects by measuring plasma disappearance values and specific organ uptakes. A pharmacokinetic compartmental model was derived, containing explicit parameters for blood flow, diffusion constants, and ECW spaces separately for each organ. Precise fitting of experimental bromide data was achieved for the rat; satisfactory fitting was also achieved in man from more limited plasma and biopsy data.


Transient force responses in blood-perfused papillary muscle after step changes in load. In in situ canine papillary muscles, we studied transient responses in peak isometric force at control length, after contraction was suddenly switched from isotonic contractions at various forces and isometric contractions at different lengths. Peak isometric force rapidly decreased after isotonic contractions at relatively low forces and isometric contractions at shorter lengths. In contrast, peak isometric force rapidly increased after isotonic contractions at relatively high forces and isometric contractions at longer lengths. There was no transient response when the preceding isotonic force was about half of the present peak isometric force. Magnitude and direction of the transient force response depended on magnitude and direction of the change in the mean muscle force level produced by the sudden switch of loading conditions. Transient force responses were accompanied by simultaneous changes in time to peak isometric force in the same direction. We proposed that, in the blood-perfused papillary muscle, a sudden change in the mean muscle force causes an abrupt change in coronary flow supply-demand relation which in turn causes a transient change in contractile force.


Species differences in responses to hyperosmolality and D600 in cat and rat heart. The direct inotropic effect of hypertonic mannitol was compared in isolated rat and cat papillary muscles. The inotropic effects of paired electrical stimulation and D600 were also evaluated in the same species. At extracellular calcium concentrations of 2.5 mM, hypertonic mannitol (25--100 mosmol/kg H2O above normal) depressed contractility in isolated rat myocardium; hyperosmolality exerted a positive effect only when extracellular Ca2+ was low (e.g., 0.3 mM). Paired pacing exerted a small but significant inotropic effect in rat heart when extracellular Ca2+ was 2.5 mM, and a larger effect at lower Ca2+. As previously noted, hypertonic mannitol and paired pacing both produced significant positive effects in isolated cat heart at an extracellular Ca2+ concentration of 2.5 mM. D600 exerted less of a depressant effect on contractility in rat than in cat heart at concentrations of 10(-6)--10(-7) M. The data suggest that 1) in contrast to results in cat heart, the positive inotropic effect of hyperosmolality in isolated rat cardiac muscle is apparent only when extracellular calcium concentration is reduced; 2) the inotropic effect of paired pacing in rat heart is greatest at low Ca2+ levels, but persists to a lesser degree at extracellular calcium concentrations of 2.5 mM; and 3) D600-inhibitable calcium channels appear to be relatively less important in the maintenance of cardiac contractility in rat than in cat cardiac muscle.


Norepinephrine uptake as an indicator of cardiac reinnervation in dogs. To study the possible role of uptake of [3H]norepinephrine ([3H]NE) as an indicator of sympathetic reinnervation of the surgically denervated canine heart, uptake was determined from multiple areas of hearts at various stages of reinnervation (1--6 mo), and these data were correlated with myocardial catecholamine content and functional response of the heart to electrical stimulation of the sympathetic nerves. Our experiments confirm that NE content correlates poorly with the degree of reinnervation of the previously denervated canine heart. There is, however, a progressive increase of [3H]NE uptake from 1 mo to 6 mo, at which time uptake has returned to approximately 57% of control values in the left atrium. The development of the storage mechanism lags far behind the specific-membrane mechanism for uptake in the reinnervating surgically denervated canine heart.


Effect of uranyl ions on isometric contractions in rabbit atria. The effects of uranyl ions on isometric contractions of atrial strips of rabbit heart were studied. It was observed that uranyl ions, in a concentration of 1.1 X 10(-5) M, do not alter isometric contraction; 2.2 X 10(-5) M concentration produced a small positive inotropic effect that was magnified at a 4.5 X 10(-5) M concentration; concentrations greater than 1.8 X 10(-5) M produced a negative inotropic effect. There is evidence that the positive inotropic effect is mediated by catecholamine release, in a similar manner to the action of uranyl ions on intestinal smooth muscle preparations. This response was blocked by propranolol and also after tyramine treatment of the preparation. The negative inotropic effect seems to be mediated by a blocking effect on calcium entry through the sarcolemma during activation. Indirect evidence supporting this hypothesis was the observation of a decrease of action of uranyl ions in the presence of isoproterenol and of increased extracellular calcium concentration.


Autonomic control of pacemaker activity in the atrioventricular junction of the dog. A stable atrioventricular (AV) junctional rhythm was induced in open-chest, anesthetized dogs by injecting pentobarbital into the sinus node artery. A factorial experimental design was used to quantify the changes in AV junctional rate as a function of the frequency of cardiac sympathetic and parasympathetic stimulation. The AV junctional pacemaker cells were more responsive to autonomic neural stimulation, but the vagal-sympathetic interactions were less pronounced than had previously been observed for the SA nodal pacemaker cells. In a group of seven animals, sympathetic stimulation at a frequency of 1.4 Hz increased the AV junctional rate by 102% from a control rate of 54 beats/min. In the same animals, vagal stimulation at a frequency of 8.4 Hz reduced the AV junctional rate by 56%. In three other animals, the AV junction was even more responsive; equivalent chronotropic effects were achieved with stimulation frequencies that were only about one-third of those cited above. There was a moderate, but significant, autonomic interaction: in the group of seven animals, the positive chronotropic effect of sympathetic stimulation at 1.4 Hz was 72% greater at the low level (0 Hz) than at the high level (8.4 Hz) of vagal activity.


Platelet removal from the circulation by the liver and spleen. Previous studies on the clearance of intravenously administered platelets have focused primarily on the long-term survival of platelets rather than the mechanisms responsible for the rapid removal of altered platelets from the blood. In the present study the short-term blood clearance and organ localization of circulating labeled platelets were evaluated in rats during particle induced reticuloendothelial (RE) blockage and after intravenous injection of increasing platelet loads in normal rats. Platelet disappearance conformed to a two-compartment exponential clearance with quantifiable rapid (K1) and slow (K2) rate constants. As platelet load increased, the rapid rate constant decreased. This clearance alteration was associated with a decrease in the percent of the injected platelet load localized in the liver and an increase in lung localization. During RE blockade, a decrease was observed in the clearance rates of both the rapid and slow compartments. Such clearance alterations were associated with decreased hepatic platelet localization and increased pulmonary and splenic platelet localization. Thus, the hepatic reticuloendothelial system may represent a rapid cellular clearance system for altered platelets. When this cellular system is impaired or overloaded, the consequences are decreased hepatic and increased extrahepatic platelet localization.


Frequency analysis of coronary intercapillary distances: site of capillary control. Frequency distributions for minimum intercapillary distance (ICD) and functional ICD were characterized for rat heart in situ. Minimum ICD denotes spacings between adjacent capillaries whether they contain erythrocytes or not. Functional ICD is defined as spacings between contiguous capillaries perfused with erythrocytes. Minimum ICD was well fitted by both the gamma and the lognormal distributions. Functional ICD was well fitted by the lognormal, but not by the gamma, or by any mixture of the gamma with another discrete distribution. The frequency analysis is interpreted to mean that: 1) A control site distal to the true arteriole exists. This is presumably the precapillary sphincter. 21 Intercapillary anastomoses help keep the diffusion path in myocardium short and comparatively uniform. 3) Complete closure of arterioles does not occur in the unstressed heart. 4) Blood flow and conditions for diffusion can be controlled independently.


Procoagulant activity of peritoneal leukocytes: effects of cortisone and endotoxin. Procoagulant activity of peritoneal leukocytes from rabbits given cortisone acetate, endotoxin, and both materials was measured in studies designed to test the hypothesis that cortisone acetate prepares rabbits for the generalized Shwartzman reaction by enhancing leukocyte procoagulant activity. Two types of peritoneal leukocyte suspensions were examined: mixed granulocyte-macrophage suspensions and macrophage suspensions. In both types, procoagulant activity could be accounted for by the number of macrophages in the suspensions. Cortisone alone did not affect the procoagulant activity, whereas endotoxin increased the procoagulant activity. Suspensions from animals given both cortisone and endotoxin varied in activity depending upon cell composition. Granulocyte-macrophage suspensions had less apparent procoagulant activity than suspensions with endotoxin alone. In contrast, macrophage suspensions--particularly sonicated suspensions--had greater procoagulant activity than those with endotoxin alone. The ability of cortisone acetate to increase macrophage procoagulant activity after endotoxin could represent one mechanism whereby cortisone acetate prepares rabbits for the generalized Shwartzman reaction after endotoxin.


Myocardial nuclear protein kinases during postnatal development. Chromatin template activity of isolated rat myocardial cells declines progressively during the first few weeks of postnatal life, a time period also characterized by restriction in myocardial proliferative capacity. Multiple protein kinases have been isolated from the nuclei of myocardial cells. Protein kinase activity decreased progressively during the first 3 wk of postnatal development, mostly in two fractions (III and V). Cyclic AMP dependency, substrate specificity, and phosphorylation patterns of endogenous substrates did not change appreciably with age. Higher phosphorylating activity of protein kinases from younger rats correlated with increased capacity to enhance myocardial RNA synthesis in vitro. This suggests the possibility that the decrease in chromatin template activity with age may be, in part, related to the decline in nuclear phosphokinase activities.


Neural pathways of a cardiogenic hypertensive chemoreflex. Excitation of a cardiac chemoreceptor with 5-hydroxytryptamine (serotonin) produces a complex autonomic reflex which includes hypertension, changes in heart rate and contractile force, and disturbances of AV conduction. This study examines the afferent and efferent neural pathways of this autonomic reflex in 60 anesthetized dogs. We used cooling and sectioning techniques in 40 of these, and in 20 others recorded afferent neurograms. The most common afferent pathways for the reflex were found in the left and right recurrent cardiac nerves. No preferential efferent routes to the heart were found, although the nature of the reflex cardiac response could be altered by specific nerve interruption. Cyproheptadine (1 mg/kg iv) regularly abolished both the reflex and the chemoreceptor afferent neural traffic, but injection of a 10 times higher concentration of serotonin (1 mg/ml) readily surmounted the blockade and restored the chemoreceptor neural traffic. Thus cyproheptadine interdicts the reflex at the site of its initiation.


Regional blood flows measured in conscious rats by combined Fick and microsphere methods. Regional blood flow measurements made by the radioactive microsphere technique were studied in conscious rats. A femoral arterial reference sample blood flow was measured directly, and at the same time indirectly by the combined use of direct Fick cardiac output and microsphere techniques. A significant correlation (r = .81, P less than .01) was obtained between direct and indirect blood flow values when 200--400 microspheres were trapped in the reference sample. When 100--200 microspheres were trapped, regional blood flow was 32% below true flow (P less than .01); and cardiac output, calculated by the reference sample method, was 57% greater than Fick cardiac output (P less than .01). When three consecutive Fick determinations and microsphere injections (20,000 per injection, 15 micrometer diam) were made in conscious rats, significant correlations were obtained among the first, second, and third regional blood flow measurements (r = .95, P less than .01). The results have demonstrated that cardiac output and reference blood flow can be measured with accuracy and precision in the conscious rat by the radioactive microsphere procedure.


Techniques for arteriography and hydraulic analysis of coronary stenoses in unsedated dogs. This report describes techniques for obtaining pressure flow characteristics and arteriograms of controlled coronary stenoses in unsedated, trained dogs. Coronary flow velocity was recorded by calibrated Doppler velocity transducers linear to three times maximum coronary flow velocity. Pressure losses across stenoses were measured by a differential pressure transducer through small catheters implanted in the distal and proximal left circumflex coronary artery or ascending aorta, a system that was linear within +/-5% to 30 Hz. Coronary stenoses were produced by saline-filled, perivascular cuff constrictors inflated to constant pressure by a pressure regulator. Catheters were implanted in the pulmonary artery for injection of intravenous drugs or diffusible radionuclides and in the left atrium for injection of radionuclide microspheres. Contrast medium was injected through the proximal coronary catheter, and high-resolution arteriograms were obtained by single-spot filming on ultra detail X-ray film and cassettes at end diastole by triggering X-ray exposures from the electrocardiogram. In 13 dogs studied consecutively, the surgical mortality was 15.4%. All implanted instruments functioned for an average of 8 wk per dog.


Glucocorticoid receptors in the guinea pig. In cytoplasmic fractions of liver and kidney prepared from adrenalectomized guinea pigs, tritiated dexamethasone ([3H]DM) is bound with a very low affinity (Kd 4 degrees C greater than or equal to 2 X 10(-7) M). By competition studies, the specificity of this binding was shown to be comparable with that for [3H]DM binding to glucocorticoid receptors in other species. In addition, cytoplasmic preparations from guinea pig liver and kidney appear to inhibit the binding of [3H]DM to rat glucocorticoid receptors under a variety of experimentally determined circumstances. It is proposed that such inhibitory activity may reflect a system of [3H]DM sequestration, perhaps by metabolizing enzymes with a high combining power for glucocorticoids. Both low affinity glucocorticoid receptors and avid binding to sites of metabolism may represent additive cellular bases for the apparent corticoresistance of the guinea pig.


Controlled cellular energy conversion in brown adipose tissue thermogenesis. Brown adipose tissue serves as a model system for nonshivering thermogenesis (NST) since a) it has as a primary physiological function the conversion of chemical energy to heat; and b) preliminary data from other tissues involved in NST (e.g., muscle) indicate that parallel mechanisms may be involved. Now that biochemical pathways have been proposed for brown fat thermogenesis, cellular models consistent with a thermodynamic representation can be formulated. Stated concisely, the thermogenic mechanism in a brown fat cell can be considered as an energy converter involving a sequence of cellular events controlled by signals over the autonomic nervous system. A thermodynamic description for NST is developed in terms of a nonisothermal system under steady-state conditions using network thermodynamics. Pathways simulated include mitochondrial ATP synthesis, a Na+/K+ membrane pump, and ionic diffusion through the adipocyte membrane.


Hypothalamic thermosensitivity in conscious Pekin ducks. Conscious Pekin ducks with chronically implanted hypothalamic thermodes were submitted to thermoneutral (Ta 25 degrees C), cold (Ta 5 degrees C), and warm (Ta 33 degrees C) ambient temperatures. Hypothalamic temperature (Thy) was varied in nine steps between 27.9 and 43.5 degrees C in repeated experiments. Cooling of the hypothalamus induced a fall of core temperature (Tc) that was linearly related to Thy and amounted to 1.1--1.3 degrees C at highest cooling intensity. The decrease of Tc was caused by inhibition of metabolic heat production and/or vasodilatation in the skin at cold and thermoneutral Ta and by activation of panting at warm Ta. After the end of cooling a temporary overshoot of heat production occurred, the degree of which depended on the degree of cooling and on Ta, and led to a rapid normalization of Tc. Warming of the hypothalamus induced a slight fall of Tc due to a reduction of metabolic heat production at cold and thermoneutral Ta and to an activation of panting at warm Ta. It is concluded that no specific cold reception and a weak specific warm reception exist in the duck's hypothalamus. A "nonsensory" temperature susceptibility of hypothalamic control functions is responsible for those reactions of thermoregulatory effector activities which do not fall into the categories of adequate thermoregulatory responses to a central thermal stimulus.


Evidence that the amount of food consumed in early life fixes appetite in the rat. Rats were raised in litters of 22 (low caloric intake) or litters of 4 (high caloric intake). At the end of 62 wk, rats from large litters were approximately 140 g lighter than those from small litters even though all animals were permitted unrestricted access to food after weaning. One factor responsible for the smaller body size was a lower voluntary food intake after weaning (8,188 +/- 205 g vs. 9,808 +/- 193 g; P less than 0.001). These results provide evidence that the amount of food consumed during suckling plays an important role in determining the habitual food intake of rats in later life. In a separate experiment, rats were raised in litters of 4, 13, 17, or 22. The results show that as litter size increased from 4 to 22, a corresponding reduction in the voluntary intake of food occurred. These results provide evidence that by controlling the food intake of the newborn rat it is possible to "program" the animal for a desired voluntary food intake in later life.


Cutaneous blood flow during heating and cooling in the American alligator. Nine alligators, Alligator mississippiensis, were injected with 133Xe and the clearance half times measured in response to heating and cooling. Mean half times for thermostable, heating, and cooling conditions were 12.2, 8.6, and 28.3 min, respectively, indicating cutaneous vasodilation in response to local heating and reduced blood flow during cooling. Alterations of cutaneous blood flow occurred before changes in body temperature or heart rate. Warming portions of the animal while shading the injection site resulted in reduced blood flow when heat loss occurred. Skin thickness (S in cm) was related to body mass (M in kg) as S = 0.08 M0.38. Cutaneous blood flow per unit area was found to increase with increasing body mass from approximately 0.0025 to 0.025 ml blood-cm-2 of skin-min-1 during warming and from 0.0018 to 0.0045 during cooling for the 0.18--8.6 kg animals, respectively.


Feeding responses of rats with dorsomedial hypothalamic lesions given ip 2DG or glucose. The glucoprivation effects of 2-deoxy-D-glucose (2DG) on feeding behavior were studied in rats with bilateral lesions of the dorsomedial hypothalamic nucleus (DMN) and sham-operated controls. The lesioned and sham-operated rats were injected intraperitoneally with 2DG (5% wt/vol) at doses of either 150 mg/kg, 300 mg/kg, or 500 mg/kg, or with saline ("control days"). At all doses significantly more sham-operated rats ate and showed an increased food consumption during the first few hours after 2DG injection when compared to saline control days. However, their 24-h food consumption was normal or less than normal, depending on the dose of 2DG. On the other hand, rats with DMN lesions (DMN-L) did not increase their food consumption during the 4 h after the injection at any of the 2DG doses. In a second experiment DMN-L and sham-operated controls were injected intraperitoneally with glucose (1.36 g/kg body wt or 2.72 g/kg body wt) or saline after an overnight fast. Glucose loads, compared to saline injections, significantly depressed the controls' food consumption only during the first hour of refeeding. On the other hand, glucose injections did not depress food intake of the DMN-L rats. It is suggested that DMN lesions may have either destroyed glucoreceptors in the DMN that monitor glucose or the glucoprivation effects caused by 2DG and/or glucoreceptive pathways that pass through the DMN.


Proton semiconductors and energy transduction in biological systems. Energy transduction processes in biology are analyzed in terms of ordered chains of hydrogen bonds. The theory is an extension of studies on proton conductance in ice and is stimulated by current ideas on the role of hydrogen ions in oxidative phosphorylation and photophosphorylation. The possibility of a protochemistry paralleling electrochemistry is presented along with experimental evidence. The theory relating transmembrane electrochemical potential difference of hydrogen ion concentration to the synthesis of ATP is reviewed. The thermodynamics of hydrogen transfer across a membrane is treated including electrochemical and electromechanical factors. As a prelude to considering ATP synthesis, the acid-base dissociation reactions of ATP, ADP, and phosphate are analyzed. The thermodynamics of ATP synthesis is discussed and a detailed model is presented coupling the synthesis to proton transport. The model assumes a gated proton semiconductor that carries protons and allows them to interact specifically with well-defined substrate molecules. The physics of proton transport is outlined and various methods examined in the context of biological membranes. Emphasis is placed on solid-state proton semiconductors and the present theory of such structures is given. A section is included on possible biological applications of these semiconductors.


Polarity of effects of stimulation of Auerbach's plexus on longitudinal muscle. The effects of repetitive electrical stimulation of nodes in Auerbach's plexus on the longitudinal muscle of rabbit intestine were investigated. Peeled longitudinal muscle strips, with adherent Auerbach's plexus, were obtained and placed under a stereodissecting microscope.  Neural elements within nodes of Auerbach's plexus were stimulated repetitively using a metal microelectrode with tip diameter of 5 micrometer. Stimuli applied to a node generally caused excitation of the longitudinal muscle on the oral side and inhibition on the anal side of the point of stimulation. Excitation of the muscle was mainly cholinergic, and inhibition of the muscle was nonadrenergic.  From the results of the present study the concept of the law of the intestine, excitation above and inhibition below the stimulated spot, was supported.


Secretory effects of secretin on isolated perfused porcine pancreas. The effect of pure natural porcine secretin on endocrine and exocrine pancreatic secretion was studied in the totally isolated perfused porcine pancreas. The exocrine pancreatic responses to secretin correspond well with those obtained in the anesthetized pig. The lowest concentration of secretin observed to increase pancreatic secretion was 2.8 pmol/liter, whereas the maximum pancreatic responses were obtained at a secretin concentration of 92 pmol/liter. The infusion of secretin in concentrations ranging from 2.8 to 278 pmol/liter in the presence of a constant concentration of glucose (7.5, 5.0, or 3.5 mmol/liter) was without effect on the insulin and glucagon release. Infusion of secretin at a concentration of 834 pmol/liter in the presence of glucose at 7.5 mmol/liter provoked a significant (P less than 0.01) short-lived increase in insulin secretion. However, there was no effect on the glucagon secretion. The results of this study indicate that neither the augmented insulin response nor the suppression of glucagon elicited by oral glucose depend on secretin.


Secretory effects of VIP on isolated perfused porcine pancreas. We studied the secretion of insulin, glucagon, and the exocrine secretion of the isolated perfused porcine pancreas in response to vasoactive intestinal polypeptide (VIP) in concentrations ranging from 30 to 18,750 pmol/liter at various concentrations of glucose in the perfusion medium. VIP stimulated the insulin and glucagon secretion in a dose-dependent manner. The response pattern was critically dependent on the glucose concentration. In the presence of a glucose concentration of 7.5 mmol/liter, VIP enhanced insulin release without affecting glucagon release. Maximal insulin release was obtained at a VIP concentration of 3,750 pmol/liter. At a glucose concentration of 5.0 or 3.5 mmol/liter, VIP enhanced glucagon release but not insulin release. VIP stimulated the exocrine secretion in a secretin-like manner. The lowest concentration of VIP observed to increase pancreatic exocrine secretion was 30 pmol/liter, whereas the maximal pancreatic exocrine responses were not obtained.


Organ culture studies of rat antrum: evidence for an antral inhibitor of gastrin release. The regulation of gastrin release in rodent antral mucosal organ cultures was investigated. The tissue was well preserved morphologically and medium gastrin concentration increased steadily throughout a 24-h culture period. The effects of peptone and a bovine serum albumin digest on gastrin release were independently investigated. During the periods these agents were in contact with the tissue, medium gastrin concentration did not differ from those of control cultures. However, treatment cultures released a significantly greater amount of gastrin into the medium than did control cultures during the two posttreatment periods.  Prolongation of the period of exposure to peptone did not alter this secretory pattern. The rise in medium gastrin concentration that followed the removal of peptone was directly related to the medium peptone concentration and was partially inhibited by readdition of peptone to cultured antral explants. These results suggest that substances which stimulate gastrin release in vivo may cause the accumulation of an antral inhibitor of gastrin release when exposed to rat antral mucosa in culture.


Rat lingual lipase: factors affecting enzyme activity and secretion. The lingual serous glands of rat tongue secrete a potent lipase that acts in the stomach in which it initiates the digestion of dietary fat. The subcellular localization of the enzyme and factors affecting its activity and secretion were studied in adult male Sprague-Dawley rats. In a fraction rich in secretory granules, 42% of the lipase content of lingual serous glands was recovered after fractionation of homogenates of discontinuous gradients of urografin in 0.3 M sucrose. Lipase secretion was stimulated by isoprenaline: 2 h after isoprenaline administration, the lipase content of lingual serous glands was 73 +/- 5% lower than that of the control group. Accumulation of lipase began 8 h after the injection, reaching 57 +/- 7% of the initial level of the control group after 25 h. Bilateral resection of the glosso-pharyngeal nerves or bilateral sympathectomy led to a 40--50% decrease of enzyme activity in 7 days. Enzyme activity was markedly affected by the fat content of the diet. Feeding a high-fat diet (22% corn oil) for a period of 2 wk led to a 45% increase in the lipase content of lingual serous glands. The exponential rise in the lipase activity of the lingual serous glands immediately after birth could be related to the high-fat content of rat milk. The data suggest that the lingual serous glands are similar to other exocrine glands such as pancreas and parotid gland in the subcellular localization of secretory enzymes and mechanisms of enzyme secretion.


Smooth muscle mechanical responses in vitro to bethanechol after progesterone in male rat. Male Sprague-Dawley rats were pretreated subcutaneously with either progesterone (3 mg/kg per day) in a vehicle or a vehicle only for 3 days. Antral and gastroduodenal junctional tissues (GJT) were excised from both groups of animals and prepared for in vitro mechanical measurements. Responses from the circular muscle axis of these tissues were recorded with strain gauge transducers over a 30-min period. Chemical stimulation of the tissue was achieved with a muscarinic agonist, bethanechol chloride. Log-dose response curves suggested that untreated antral tissue generated stronger contractile activity than untreated GJT on an equal weight basis at bethanechol dose levels of 6.4 X 10(-6) M to 1 X 10(-4) M (P less than 0.005). Antral tissue and GJT contractile activity from the progesterone pretreated animals was significantly reduced (P less than 0.01) compared to the corresponding tissues from untreated animals at bethanechol dose levels of 6.4 X 10(-6) M and 1.28 X 10(-5) M. Progesterone pretreatment appeared to have little effect on the contractile frequency of either tissue. These results suggest possible progesteronic influences on contractile force in gastrointestinal smooth muscle.


Effects of solute-coupled transport on lymph flow and oncotic pressures in cat ileum. The effects of net volume absorption rate on steady-state lymphatic and capillary volume flows, lymphatic protein flux, and lymph oncotic pressure were analyzed in an isolated vascularly perfused cat ileum preparation. Solute-coupled fluid transport was stimulated by instilling either Tyrode solution, Tyrode + glucose, Tyrode + taurocholic acid (TC), Tyrode + TC + oleic acid, or Tyrode + aspartic acid, into the ileal lumen. Lymph flow increased in a sigmoidal fashion as net volume absorption rate increased. A linear relationship was observed between lymphatic protein flux and net volume absorption rate. The relative contributions of the intestinal capillary and lymphatic systems in removing absorbed volume from the mucosal interstitium was highly dependent on the rate of net volume absorption. Lymph oncotic pressure decreased progressively as net volume absorption rate increased with a maximal reduction in lymph oncotic pressure of 6.0-7.0 mmHg at the higher volume absorption rates. The results of this study indicate that 1) the rate of solute-coupled fluid transport greatly influences the rate of intestinal lympathic and capillary volume flows, lymphatic protein flux, and lymph oncotic pressure, 2) a reduction in tissue oncotic pressure may serve as the major driving force for vascular removal of absorved volume, and 3) the increase in capillary permeability to plasma proteins during fluid transport is related to the rate of volume absorption.


Development of the circadian rhythm of jejunal sucrase activity in the weanling rat. In the adult rat, fed ad libitum, the activity of jejunal sucrase shows a diurnal rhythm with a peak during the dark period. Ontogenically, sucrase activity appears around the 16th postnatal day, then rises rapidly, and reaches adult levels by the 25th day. Our aim was to determine the developmental stage at which the diurnal rhythm appears and to elucidate its physiological basis. When sampled every 3 h on the 19th day, jejunal sucrase showed no discernible pattern with time. In contrast, at 22 days (1 day after completion of weaning) a circadian rhythm very similar to that of adults had appeared. Weights of stomach contents showed that the adult pattern of nocturnal feeding also matured between days 19 and 22. When weaning was prevented, no sucrase rhythm was detected on day 22, despite an imposed rhythm of suckling. Thus the sucrase rhythm is normally cued by some aspect of weaning other than rhythmic ingestion per se. Although corticosterone seemed a likely mediator of the sucrase rhythm, studies in adult rats showed that the rhythm persists in adrenalectomized animals.


Effect of atropine and vagotomy on pancreatic polypeptide response to a meal in dogs. In four conscious dogs the pancreatic polypeptide (PP) response to a standard beef-liver meal was measured by specific radioimmunoassay and compared with the response seen after the intravenous injection of 25 or 100 microgram/kg atropine. All three tests were performed twice in each animal and then repeated after truncal vagotomy. The mean prevagotomy postprandial PP increment was 85 +/- 16 pmol/liter in the first 2-h period and 54.5 +/- 13 pmol/liter in the second. After the injection of 25 microgram/kg atropine there was significant reduction in the early response (mean delta PP = 39 +/- 17 pmol/liter, P less than 0.05), but not the late (mean delta PP = 62 +/- 18 pmol/liter). After 100 microgram/kg atropine sulfate, the response was significantly reduced during both periods (mean delta PP = 5.5 +/- 5.2 and 20 +/- 8.8 pmol/liter, respectively, P less than 0.01). Truncal vagotomy significantly (P less than 0.01) reduced the PP response over both time periods (mean delta PP = 6.4 +/- 2.2 and 5.8 +/- 3.8 pmol/liter), and the small residual response was completely abolished by atropine. In five additional dogs an infusion of bethanechol (100 microgram . kg-1.h-1) caused a significant increase (P less than 0.05) in the plasma concentration (mean delta PP = 40.9 +/- 11.8 pmol/liter), which was abolished by pretreatment with atropine (mean delta PP = -2.9 +/- 2.1 pmol/liter). These studies suggest that PP release in response to a meal in the dog is largely under vagal-cholinergic control.


Concentrative PAH transport by rabbit kidney slices in the absence of metabolic energy. Characteristics of para-aminohippurate (PAH) transport in the absence of intracellular metabolism were studied with Na+, K+-depleted and ouabain-poisoned rabbit kidney cortex slices. The imposition of a NaCl gradient (out to in) resulted in specific stimulation of PAH uptake. PAH accumulated against its concentration gradient when cell [Na+] was less than medium [Na+]. Conversely, renal cells extruded PAH when cell [Na+] exceeded medium [Na+]. Membrane potential measured with triphenylmethylphosphonium revealed that conditions which created an interior-positive membrane potential inhibited the Na+-dependent transport of PAH but caused stimulation of the Na+-independent component. Characteristics of the Na+-dependent PAH transport system in ouabain-poisoned slices were similar to those previously described in metabolically active tissues.