Vigilance performance of mildly mentally retarded adults. Mildly mentally retarded adults were compared on both an auditory and a visual vigilance task with subjects having greater than average intelligence. Contrary to results reported by Semmel (1965) using a visual task, no difference was found in the rate of decline of performance between the two groups in either of the two tasks, although overall performance of the above-average group was superior to that of the retarded group. The results offered no support for the hypothesis that mentally retarded persons suffer from a more rapid decay in arousal under conditions of reduced sensory variation. Nor did they support a suggestion that in this particular situation retarded subjects would demonstrate more inattention than would nonretarded subjects.


Immediate and delayed reward preferences of TMR adolescents. Adolescent TMR students (mean IQ = 37) were presented with a list of 32 reward options, consisting of primary (food) and secondary (cash equivalent) rewards that were immediately available or delayed one day at a ratio of 1:2. The greatest number of delay choices occurred when the decision was between immediate/secondary and delayed/primary rewards. Subjects subsequently classified as delayers (34.3% of this population) made the fewest delay choices when presented with immediate/primary vs. delayed/secondary/options. Nondelayers made the most delay choices when given an immediate/secondary or delayed/primary choice.


Facilitation of serial recall in retarded children and adolescents: verbal and kinesthetic strategies. The nature of the modality-specific effects of rehearsal training for serial recall was explored. Retarded children and adolescents were trained in either verbal or kinesthetic "cumulative rehearsal--fast finish" strategies for picture recall. Results indicated that both strategies facilitated recall on training tasks and on a transfer-recall test. No age effects or Age X Rehearsal Condition interaction resulted. These results provide support for a general cross-modality recoding explanation of rehearsal effects and suggest that retarded individuals are as capable of mediating picture recall in their sensorimotor system as well as in their verbal-auditory memory system.


Social and attentional aspects of echolalia in highly echolalic mentally retarded persons. Echolalia was examined in a sample of highly echolalic mentally retarded individuals. When presented with a standard set of questions, under conditions differing in appropriateness for exchange of discourse (e.g., questions presented with examiner and patient face-to-face vs. questions presented with the examiner's face averted vs. questions addressed towards another person sitting silently beside the patient), subjects' frequency of echolalia varied. Besides showing considerable sensitivity to aspects of discourse exchange, subjects exhibited some limited capacity for processing linguistic information.


Abortion, adoption, or motherhood: an empirical study of decision-making during pregnancy. Using matched samples (n = 249) of single, generally young black women, two thirds on welfare and previously pregnant, the study examined why some women decide to deliver while others, with almost identical sociodemographic and prior pregnancy experiences, decide to abort. Women delivering were in significantly longer relationships with partners who had also been less cooperative about contraception. Discussion with significant others occurred more often in decisions to deliver and greater support was received for that option. For many women the abortion decision and, to a lesser extent the decision to deliver, was conflictful, options evenly balanced, and considerable indecision reported. Attitudes about ethical aspects of abortion and knowledge of role models for single parenthood and seeking abortion among friends and relatives also discriminated the two samples. Women who delivered all previous pregnancies found the decision to abort particularly difficult. In this young population 29.2 per cent of women currently delivering had previously aborted; 55.8 per cent of women currently aborting had delivered. During their reproductive life, therefore, almost all women in this population will face the decision whether to abort and many will choose that option. Whether abortion or delivery is chosen will depend upon circumstances surrounding specific pregnancies rather than characteristics of the mother. Adoption is not an option in the pregnancy decision of women in this population.


Plasma oxytocin in initiation of labor.

Plasma oxytocin in initiation of labor. Serial radioimmunoassay measurements of plasma oxytocin (OT) in maternal venous blood have been carried out in 15 patients, during pregnancy, labor, and delivery. Fetal plasma OT was also measured in the blood from the umbilical vein and umbilical artery. The results indicate that: (1) during pregnancy, plasma OT is present in maternal blood; (2) the quantity of plasma OT increases with advancing pregnancy; (3) no OT surge occurs around the onset of labor; (4) the plasma OT surge occurs with cervical dilatation and vaginal distention. The data indicate that OT does not play a primary role in the initiation of labor and support the concept that OT most likely contributes to formation of prostaglandins through the uterine contractions OT produces. OT surges, frequently called spikes, have been observed to occur during pregnancy as well as during labor. During the course of labor, OT surges have been encountered in association with rupture of the membranes, vaginal examination, and descent of the vertex, and have occurred almost consistently with maximal cervical and vaginal distention. Such OT surge was suppressed by effective spinal and pelvic regional anesthesia. Therefore, this surge is consistent with the Ferguson reflex described in experimental animals, and it represents the first evidence that the Ferguson reflex, in fact, exists in human beings. Evidence is presented here that an excess of OT in fetal blood over that found in maternal plasma was associated with hypertonic, irregular, tumultuous or prolonged labor and with mild to moderate fetal hypoxia and fetal distress peculiar to abnormal uterine contractions.


Hormonal profile as a prognostic index of early threatened abortion. Twelve pregnancies, in which the initial serum hCG titer as measured by RRA was subnormal, were studied to determine if a hormonal profile would serve as a prognostic index of spontaneous abortion. Three of the 12 patients delivered term babies. The hCG titers remained subnormal throughout the pregnancy, however, the serum E2, P, 17alpha-OHP, and PRL remained normal. One of the 12 patients aborted in week 25 of gestation. The serum hCG and PRL were subnormal; however, the serum E2, P, and 17alpha-OHP were normal. Eight of the 12 patients aborted prior to 100 days' gestation. The serum hCG, E2, and PRL were subnormal whereas the P and 17alpha-OHP were normal. Therefore, in patients who have subnormal serum hCG titers, serum E2 and PRL may provide a prognostic index of spontaneous abortion.


The effects of paracervical block on uterine activity and beat-to-beat variability of the fetal heart rate. Paracervical block analgesia with the use of lidocaine hydrochloride provoked little change in uterine activity. The general trend in uterine activity was an increase, although there was considerable variation in individual response. Beat-to-beat variability in the fetal heart rate increased following the block. The increase in variability began almost immediately, with the greatest increase occurring at a time when one would expect maximum maternal and fetal lidocaine levels. It is proposed that this increase in fetal heart rate variability is an early sign of post-paracervical block hypoxemia and/or hypoxia.


Enhancement of fetal lung maturity by intra-amniotic administration of thyroid hormone. Following preliminary results in animal studies demonstrating that thyroxine (T4) injected directly into the fetus or the amniotic sac is capable of enhancing fetal lung maturity, a trial of thyroxine treatment in mean was carried out. Two hundred micrograms of T4 were injected intra-amniotically in eight women with high-risk pregnancies in which premature delivery was inevitable or indicated. Fetal lung maturity was evaluated by a recently developed, accurate, and rapid method using the microviscosity value epsilon (this being the linear expression of the polarization value P) of the lipid assembly of the amniotic fluid as a parameter of the surfactant content. epsilon Values, which were very high before T4 injection, dropped steeply to below the value of 4.344, indicating fetal lung maturity. Eight newborn infants delivered, five by caesarean section, soon after the T4 injection did not develop respiratory distress syndrome, although they were born prematurely. Intra-amniotic injection of T4 appears to be of therapeutic value in enhancing fetal lung maturity.


Unreliability of prenatal determination of fetal sex with the use of Y-body fluorescence in midcervical smears. A prospective study of midcervical smears from 71 pregnant women was carried out to investigate the validity of Y-body fluorescence as a method for determining intrauterine fetal sex. Endocervical smears were taken below the mucous plug, appropriately stained with Atabrine, and examined using male and female buccal smears as controls. Analysis of the data showed that correct sex of the baby could be predicted only 55 per cent of the time. There was little difference in prediction rate whether the smears were taken in the second or third trimester. The first-trimester smear was the least reliable.


Uterine T-mycoplasma colonization in reproductive failure. In 46 patients with a history of habitual abortion and in 18 women with primary unexplained infertility, samples from cervical mucus and endometrial tissue have been examined for presence of T-mycoplasma, and the results compared to those obtained among 45 control subjects. Colonization of T-mycoplasma in the cervix was found to be common in all patient groups (49 to 83 per cent), whereas colonization in the endometrium was found to be significantly more frequent among the habitual abortion patients (28 per cent) and the infertility patients (50 per cent) than among the control subjects (7 per cent). In all patients having T-mycoplasma-positive endometria the organism was also isolated from the cervix, thus indicating an ascending route for the colonization of the uterine cavity. Bacteria belonging to the normal vaginal flora were frequently co-isolated from the endometrial samples along with T-mycoplasma. The women with T-mycoplasma-positive endometria showed a high incidence of postabortion fever. Treatment with doxycycline eradicated T-mycoplasma from the cervix and the endometrium and apparently led to an improvement with respect to the outcome of the posttreatment pregnancies.


Endometrial and vaginal cuff bacteria recovered at elective hysterectomy during a trial of antibiotic prophylaxis. The utility of culturing the cut edge of the vaginal cuff and endometrium of the uterine specimens of patients undergoing elective hysterectomy and receiving antibiotic prophylaxis has been critically examined. Subjects for this study represent a randomized subpopulation of patients participating in a larger controlled, prospective, double-blind study of antibiotic prophylaxis which has been conducted at Yale-New Haven Hospital during the past five years. On the basis of the organisms recovered, speculation is raised concerning the existence of an endometrial flora and the mechanisms of postoperative vaginal cuff infection in patients treated and not treated with antibiotic prophylaxis at the time of hysterectomy.


A safer method for paracervical block in therapeutic abortions. Adverse reactions to paracervical block, including death, are believed to be dose related. By using a modified jet injector instead of the standard syringe-and-needle technique, we obtained equal analgesia with one fifth of the standard milligram dosage of lidocaine in patients undergoing therapeutic abortion. Blood lidocaine levels as determined by gas chromatography were reduced by two thirds with jet injection. These results led us to conclude that jet injection for paracervical block is safer than the syringe-and-needle technique.


Residency education in the 1980's.

Residency education in the 1980's. It appears that great changes in residency education will be made in the 1980's. These changes not only portend excitement and improvement, but also predicate troublesome and trying times. Medical schools must take a more active part in residency training and may ultimately take full responsibility. Educational institutions will be asked to guarantee the intellectual and technical competence of their postgraduate trainees by tightly structuring the educational effort, and this obligation rightfully inures to the medical school rather than the hospital. Training programs must develop methods of using all private populations for postgraduate education that will reach at least the level of that achieved with nonprivate patients. Training programs must utilize community hospitals, and the desirable components of academia must be introduced into these institutions. As difficult to achieve as it is simple to state, new sources of funding must be found for postgraduate education. Finally, there eventually may be a need to devise entirely new concepts of training based on career goals, and the 1980's will provide fertile ground for those faculties that wish to be imaginative and innovative.


Optic atrophy and glaucomatous cupping.

Optic atrophy and glaucomatous cupping. We reviewed 170 eyes of 112 patients with optic atrophy from various causes. Special attention was directed towards measured cup:disk ratios as well as presence of glaucomatous-like cupping of the optic nerve head. We observed a small but significant increase in nerve head cupping in eyes with optic atrophy when compared to contralateral eyes, as well as to eyes of 50 diabetic patients. No characteristic glaucomatous disk changes were documented. We evaluated these findings with respect to possible causes of glaucomatous disk and field changes.


Systemic hypotension and glaucomatous changes. We undertook a prospective study to determine the frequency of development of glaucomatous disk or field changes in a series of patients who had survived at least one episode of shock with poor peripheral tissue perfusion. In 18 patients with 26 distinct episodes of shock we were unable to demonstrate any glaucomatous disk or field changes.


Pathophysiology and electron microscopy of melanomalytic glaucoma. We examined an eye with melanomalytic glaucoma by quantitative aqueous perfusion, light and electron microscopy. Facility of outflow was markedly diminished from normal in vivo and in vitro. The trabecular meshwork was heavily laden on its surface and in the intertrabecular spaces with macrophages. Many of these cells appeared to be wandering macrophages, while some appeared to be detached, phagocytic trabecular endothelial cells.


Spectral transmittance of intraocular lenses and retinal damage from intense light sources. I measured the spectral transmittance of clear polymethylmethacrylate intraocular lenses in the 300- to 700-nm range. The near-ultraviolet transmittance of the polymethylmethacrylate lens was significantly greater than that of the crystalline lens. Therefore, the pseudophakic eye is more susceptible to retinal damage from intense near-ultraviolet light sources than the normal eye. Retinal thermal response of the pseudophakic eye was compared with that of the normal eye for near-ultraviolet radiation, and retinal thermal response to near-ultraviolet radiation was compared with that to visible light for the pseudophakic eye. Additionally, because there was no significant difference between polymethylmethacrylate and crystalline lens in visible and near-infrared transmittance, thresholds for thermal retinal damage at a given wavelength are similar for the pseudophakic and the intact eye in these spectral regions.


Chorioretinal vascular anastomoses after perforating trauma to the eye. A 32-year-old white man sustained an ocular injury with a small piece of metal. He had perforation of the retina and choroid, and later developed chorioretinal vascular anastomosis. Disabling complications, such as neovascular growth, serous transudation, or hemorrhages, did not occur within a ten-month follow-up period. Interruption of Bruch's membrane and the retinal pigment epithelium, with approximation of the normally separated vasculatures of the choroid and retina, appears necessary for such anastomoses to occur.


Ocular manifestations of group A Niemann-Pick disease. Four infants with Group A Niemann-Pick disease had similar ocular abnormalities secondary to this systemic disease. Each child demonstrated corneal opacification, brown discoloration of the anterior lens capsule, and retinal opacification with a macular cherry-red spot. These abnormalities were seen in each child during the first year of life and appeared stable. Recognition of this combination of ocular defects facilitates early identification of patients with Group A infantile Niemann-Pick disease.


Pigment epithelial proliferation in human retinal detachment with massive periretinal proliferation. Biopsy specimens from vitreous and preretinal membranes, obtained during vitreous surgery from 39 human eyes suffering from massive periretinal proliferation, were examined electron-microscopically. Analysis of the cellular membranes demonstrated mostly cells with epithelial characteristics: polarization of the cells, basal lamina formation, specialized cellular junctions, and microvilli formation. These epithelioid cells contained prominent rough endoplasmic reticulum, glycogen deposits, a multitude of cytoplasmic filaments, some resembling myofilaments, and nonmembrane bound, sometimes wedge-shaped pigment granules. Macrophages were interspersed in the membranes. There was a striking similarity of these findings to those of an experimental model of retinal detachment in owl monkeys, We concluded that most likely the described cells derived from cells of pigment epithelial origin.


Visual function in acute posterior multifocal placoid pigment epitheliopathy. We examined a 19-year-old woman with acute posterior multifocal placoid pigment epitheliopathy one week after she noted blurring of central vision. Her corrected visual acuity was R.E.: 6/7.5 (20/25), and L.E.: 6/12 (20/40). The visual fields showed 10-degree pericentral scotomas. A color vision defect and an abnormal Stiles-Crawford effect were present. Dark adaptation showed a delayed time course, with normal final thresholds. The electro-oculogram was subnormal, suggesting widespread abnormality of the retinal pigment epithelium. Active lesions resolved within three weeks, but fluorescein angiography showed characteristic widespread residual changes. Within three weeks, she had normal visual acuity and a normal electro-oculogram. Other tests of visual function showed recovery with a slower time course. By one year, the visual fields, color matching, Stiles-Crawford effect, and dark adaptation were almost normal. Analysis of the color-matching data and Stiles-Crawford effect indicated that the abnormalities of macular function were caused by an underlying lesion of the pigment epithelium and photoreceptors. This caused a physical distortion of the photoreceptor layer and metabolic disfunction of the photoreceptors.


A specific enzyme defect in gyrate atrophy. To establish the enzyme defect in gyrate atrophy, we measured the activity of ornithine aminotransferase in phytohemagglutinin stimulated lymphocytes in a patient with gyrate atrophy, her daughter, and three normal controls. The patient's cells had no detectable ornithine aminotransferase activity and the daughter's cells had 44% of control activity. This intermediate value is characteristic of an obligate heterozygote. These results are the first demonstration of an enzyme defect in gyrate atrophy.


An improved microsurgical ceiling-mounted unit and automated television. To increase the versatility of a ceiling-mounted microsurgical unit, we instructed an instrument company to redesign an existant unit according to our requirements. The modified instrument has improved microscope supporting arms capable of supporting an inserted X-Y translation stage. The unit houses diathermy, cautery, fiberoptic light source, and suction devices. Most of these devices can be exchanged for other to adapt to individual requirements. Mirror image design increases versatility. Floor-mounted outlets avoid a multitude of cables. A double color television system for automatic recording of surgery has been installed.


Symblepharon in sarcoidosis.

Symblepharon in sarcoidosis. A 38-year-old black man had developed sarcoidosis, confirmed by biopsy five years earlier. He then developed skin lesions and, at age 38, follicles and cicatrization of the upper and lower palpebral conjunctivae of both eyes. This patient had keratoconjunctivitis sicca, lacrimal gland enlargement, and cicatrization of the conjunctiva with symblepharon. Biopsies of the lacrimal gland, conjunctiva, skin, nasal polyps, and epididymis all showed sarcoidosis.


Progressive nature of pigmented paravenous retinochoroidal atrophy. A 30-year-old man with pigmented paravenous chorioretinal atrophy showed, within a relatively short time, changes that documented the progressive nature of this disease. These changes included: further constriction of peripheral visual fields; more extensive and frequently confluent areas of retinochoroidal atrophy; a scalloped appearance of lesions resembling posterior gyrate atrophy; peripheral pigment clumping; and the presence of localized atrophic areas with crystal deposition in the peripheral retina.


Punctate lenticular opacities in type II mannosidosis. Ocular examination in four siblings with Type II mannosidosis revealed scattered punctate opacities in the entire lens. No such lenticular opacities were described in 28 previously reported patients, 17 presumed Type II and 11 Type I. Complete ocular examination with particular attention to opacities in the lens and cornea may provide additional phenotypic data for identification of genetic variants with amnnosidosis.


Ocular bioavailability and systemic loss of topically applied ophthalmic drugs. We used 20-day-old rabbits as a model to show that the ocular bioavailability of topically applied pilocarpine nitrate increased as the instilled volume of the drug was decreased. Decreasing the instilled volume from 25 to 5 microliter permitted a dosage reduction of greater than 2.5 times without sacrificing overall drug concentrations in the eye. Since only a small fraction of topically applied doses to the eye actually reached the interior of the eye, the remainder of the dose was lost and available for systemic absorption. The reduction in dosage permitted by this approach resulted in less drug appearing in the general circulation, as shown by comparative plasma level-time profiles. The advantages of reducing drop size are improved ocular bioavailability permitting the use of smaller doses; and less systemic drug loss, thus reducing the potential for systemic side effects. These advantages could be especially significant in the pediatric and geriatric age groups.


Simultaneous stereophotogrammetric and angiographic fundus camera. We developed an apparatus for serial, simultaneous stereophotogrammetric fundus angiography by modifying a fundus camera. The paired stereoangiograms obtained by this system provided satisfactory stereoscopy and fair depth of field. With this system, mounting and filing of slides were easy. Accurate photogrammetric analysis of the fundus can be performed. Clinical results were impressive in both young and old subjects with fully dilated pupils.


Viable composite grafting in eyelid reconstruction. I reconstructed eyelids in two patients by successfully using a new technique to increase the viability of a composite, full-thickness eyelid graft. Splitting the graft into two components of tarsal-conjunctival-margin and skin and placing each component against a viable skin and orbicularis flap, respectively, facilitated the acceptance of the graft and increased the success of the reconstruction.


A new headrest for ophthalmic microsurgery. We designed and successfully used a new headrest for ophthalmic microsurgery. The symmetrical instrument has a U-shaped frame and is designed to be clamped to an operating table as a projecting extension. The headrest has been satisfactory for patients having either general or local anesthesia, and particularly useful for vitreous surgery with the Zeiss Mark VI microscope; this headrest gives excellent control over the visual field and eliminates all extraneous movement.


A suction tip for controlled removal of nonmagnetic intraocular foreign bodies. I used a soft-tip suction needle during a vitrectomy procedure to life glass foreign bodies away from the retina so they could be more easily and safely grasped with foreign-body extraction forceps. The use of the instrument reduces the chance of inadvertent scraping of glass fragments or instruments against the retina during the removal.


A magnet tip for controlled removal of magnetic foreign bodies. I designed a small diameter magnet tip for intraocular removal of foreign bodies, particularly at the time of vitrectomy. Advantages of the intraocular tip include: (1) reduced likelihood of scraping of the foreign body along the retinal surface while in the magnetic field; (2) reduced chance of incarcerating the retina or choroid, or both, between the magnet and the foreign body during removal. Although the intraocular tip is less strong than conventional shorter tips, it provides greater control in the removal of intraocular foreign bodies when sufficient magnet strength is present.


Relationship of cigarette smoking to congenital anomalies and perinatal death. A prospective study. Congenital anomalies caused 3.43 perinatal deaths/1000 births, as reported in a large prospective study. At all gestational ages the mortality rates progressively increased when gravidas smoked more than 10 cigarettes/day. An excessive death rate was also found in males, in offspring of mothers over 39 years of age, and in women of low socioeconomic status. Placentas associated with the malformed infants had an increased frequency of single umbilical arteries and abnormal insertions of fetal membranes and umbilical cords into the placenta.


The influence of maternal immunization on the antibody response of the offspring in genetically high-responding rats. Immunization of high responding PVG female rats with poly(Glu52Lys33Tyr15) agrregated with methylated bovine serum albumin was associated with a decreased ability of their offspring to make an antibody response to the antigen. The amount of antigen given to the mothers was important in determining the magnitude of the antibody production in the offspring. The depression of antibody production was time-dependent: the first and second F1 litters from immunized mothers had significantly decreased antibody responses while no decrease was observed in the third F1 litter. Similarly, this alteration in the antibody response could be transmitted to the F2 generation but not to the F3 generation. These results suggest that aggregated antigen persists in the mother and crosses the placenta to interact with the developing immune system of the fetus. In the high-responding PVG strain, this interaction is associated with a decreased ability to respond to the antigen at a later time.


Ultrastructural and biochemical aspects of liver mitochondria during recovery from ethanol-induced alterations. Experimental evidence of mitochondrial division. To study the morphologic and biochemical changes occuring in liver mitochondria during recovery from ethanol-induced injury, rats fed a 6-month high-alcohol regimen plus a nutritionally adequate diet which did not induce fatty liver were compared with isocalorically fed controls. After this period the alcohol-fed animals displayed striking ultrastructural changes of liver mitochondria and a decreased respiratory activity with succinate or malate-glutamate as substrate. On the contrary, the respiratory rate with I-glycerophosphate was 50% increased. Regression changes were studied after alcohol was withdrawn from the diet. Enlarged mitochondria rapidly disappeared (in 24 hours), although a few megamitochondria were still present after 8 days of abstinence. A similar recovery was observed for the functional alterations. At the end of the experimental period, only a slight decrease of the maximal respiratory rate using malate-glutamate as a substrate was noted. The ultrastructural findings and the morphometric data suggest that the way in which mitochondrial normalization takes place is based on partition of these organelles.


Experimental infarct size as a function of the amount of myocardium at risk. Occlusion of the same coronary artery at the same anatomic site in a group of dogs results in significant variation in the size of the resultant infarcts. The present study shows that much of this variation can be explained by differences in the pattern of distribution of the occluded coronary artery. The relationship between the anatomic size of an occluded coronary bed and the the amount of necrosis resulting from 40 minutes of proximal circumflex coronary (LCC) occlusion and 3 days of reperfusion was determined in randomly selected dogs using an in vitro latex coronary injection technique. The amount of necrosis, calculated from serial histologic sections taken through the posterior papillary muscle (PP), correlated closely with the size of the occluded coronary bed: 5 dogs with small LCC beds (26 +/- 2%) had 10 +/- 3% PP necrosis; 5 dogs with medium-sized LCC beds (37 +/- 2%) had 33 +/- 1% necrosis; and 7 dogs with large LCC beds (42 +/- 1%) had 51 +/- 2% necrosis. The results show that much of the variability in infarct size among dogs subjected to coronary artery occlusion at the same anatomic site is a function of differences in ischemic bed size. Grouping dogs by occluded coronary bed size may improve the resolution of experimental studies testing the effect of various therapies on infarct size.


Spontaneous amyloidosis in LLC mice.

Spontaneous amyloidosis in LLC mice. Practically all low leukocyte count (LLC) mice over 1 year of age develop renal amyloidosis. Renal amyloid is deposited in the glomeruli and in the interstitium between the convoluted as well as collecting tubules, with consequent development of cysts and necrosis. LLC mice die of chronic renal failure. Electron microscopic studies reveal amyloid fibrils in the mesangium, a thickening of the basement membranes, and fusion of the foot processes in the glomeruli. Massive amounts of amyloid fibrils are also present in the interstitium, where intracellular fibrils in the fibroblasts as well as in the tubular epithelium cells are found. Vesicles, which are probably formed from membrane disruption, and amorphous materials are seen along the basement membranes. LLC mouse amyloidosis is discussed with regard to its potential as a model for studies on amyloidosis as well as the etiology and origin of amyloid fibrils.


X-ray microprobe analysis of Michaelis-Gutmann bodies in human and experimental malakoplakia. Using x-ray microprobe analysis, we studied Michaelis-Gutmann bodies (M-G bodies) in malakoplakia tissue samples from human kidney and testis as well as from lesions experimentally induced in the rat. In all the M-G bodies tested we could unambiguously detect calcium at both its Kalpha and Kbeta lines. The actual amount of calcium depended on the developmental state, ie, on the degree of calcification of the M-G body, In M-G bodies of rat kidney malakoplakia tissue fixed without osmium tetroxide, the phosphorus could also be detected unambigously. From the ratios of calcium and phosphorus percentages (w/w) we concluded that CaHPO4 was present. No difference was found between M-G bodies in malakoplakia tissues of human origin and those in experimentally induced malakoplakia.


The hepatic effects of hypolipidemic drugs (clofibrate, nafenopin, tibric acid, and Wy-14,643) on hepatic peroxisomes and peroxisome-associated enzymes. Male Swiss-Webster mice were fed diets containing four hypolipidemic agents which are known to induce proliferation of hepatic peroxisomes. Treatment with all four drugs (clofibrate; its structural analogue, nafenopin; and two drugs structurally unrelated to clofibrate, tibric acid and Wy-14,643) produced a marked hepatomegaly in the mice. The extent of the increase in liver weight correlated well with the increases in total hepatic DNA and in the collective volume of hepatocyte peroxisomes. Treatment with these drugs also produced similar increases in the activities of peroxisome-associated enzymes. The most dramatic increases were noted in the activities of the short-chain (8- to 26-fold) and medium-chain (4- to 11-fold) carnitine acyltransferase. Significant increases were also noted in the activities of catalase (twofold to threefold), alpha-glycerophosphate dehydrogenase (twofold to threefold) and the long-chain carnitine acyltransferase (twofold to fourfold). Activity of the latter enzyme, however, is not known to be associated with peroxisome fractions. Concomitant administration of actinomycin D or cycloheximide with a single oral dose of clofibrate diminished the increases in liver weight and carnitine acyltransferase which occurred with clofibrate treatment alone. The finding that the major increase in activity of peroxisome enzymes occurred in those associated with metabolism of acyl CoA groups supports the hypothesis that the hypolipidemic action of the drugs and the proliferation of hepatic peroxisomes are related functions.


Pathways upstream: risks and realities of early screening efforts. The need for basic societal institutions to foster growth-enhancing and ego-strengthening experiences is highlighted. The ascendancy of Asklepios--as representative of the remedial, medical model--over Hygeia--symbolizing the preventive, public health approach--is traced from Hellenic mythology to present reality. The Hygeian merits of current early identification programs are considered, and means for moving them closer to the Hygeian ideal are suggested.


Parental treatment, children's temperament, and the risk of childhood behavioral problems: 2. Initial temperament, parental attitudes, and the incidence and form of behavioral problems. Childhood behavioral problems are found to be related to both early temperament and parental behavior, in that first-year temperament scores predicted mild (but not more severe) problems. A parental pathology scale discriminated more severe cases among girls only; more severe cases among boys were accompanied by negative temperament changes. For both sexes, the form of subsequent behavioral problems was associated with first-year temperament patterns.


Interaction of language development and activity level on performance of first-graders. Developmental theory suggests that language may be a compensatory factor in the cognitive functioning of hyperactive children. A comparison between first-graders of high activity level and those of low activity level provided support for this theory. Language maturity emerged as a significant variable in task performance and overall school achievement for the high-activity-level group only.


Ethnicity and service delivery.

Ethnicity and service delivery. This paper reports research representing part of a systematic effort to operationalize ethnic issues in service delivery. An attitude scale was developed and applied to a national sample of child welfare workers and to minority workers in innovative ethnic settings. Significant differences were found related to sample, age, ethnicity, and agency type.


Sharing the crisis of rape: counseling the mates and families of victims. The involvement of mates and family members in counseling interventions designed to help victims of rape in their post-traumatic reconstitutive efforts is critical. Suggestions are offered for assisting those close to the woman in their attempts to explore and articulate feelings and concerns about the crisis.


The remembrance of things past: on the collection and recollection of ingredients useful in the treatment of disorders resulting from unhappiness, rootlessness, and the fear of things to come. Lack of hope for future change is hypothesized as a distinguishing factor between suicidally depressed young adolescents and other young people who are also objectless, the developmentally dispossessed. Methods by which the affective reserve of hope and self-love can be therapeutically augmented are suggested, and speculations are offered on the role of the personal past and group past in generating hopefulness in the nonclinical population.


Sweden's approach to health screening for preschool children. The findings of a recent study of the approach taken by Sweden to a perceived problem in that nation's child health care system are reviewed. The Swedish experience is discussed in terms of its application to the United States, with particular reference to EPSDT and the newly proposed Child Health Assessment Program.


Problem kids and preventive medicine: the making of an odd couple. This paper maintains that the preventive medical model is inappropriate for dealing with childhood developmental disorders. The history of preventive medicine is traced briefly, and its adoption by the mental hygiene, child guidance, and community mental health movements is discussed. It is concluded that a program of screening, diagnosis, and treatment for poor children will have negative consequences for those it is meant to serve.


An approach to identification and prevention of developmental difficulties among Mexican-American children. This paper reviews the relevant literature and discusses the nature of Chicano concerns in regard to the implementation of legislation mandating developmental assessment of poor children. An approach to providing screening and remedial services responsive to the needs of Mexican-Americans is outlined.


Dynamic stiffness of rabbit mesotubarium smooth muscle: effect of isometric length. The dynamic stiffness of mesotubarium smooth muscle from nonpregnant adult rabbits was measured continuously during isometric contraction by applying small (0.5 percent of the muscle length) sinusoidal length perturbations and measuring the amplitude and phase of the resulting tension perturbations. Stiffness during contraction was directly proportional to muscle tension; during relaxation stiffness at all tensions was significantly increased as compared to the values encountered during the rise of tension. Peak isometric tension and dynamic stiffness (determined at a common tension level) both decreased at shorter muscle lengths; the relative falloff in stiffness was significantly less than the tension decrease. Varying levels of muscle activation (obtained by changing stimulus strength and by applying quick releases to active muscle) had little effect on the measured elastic modulus. Comparisons of these results with published data on single-cell contractile properties imply a cellular locus for a portion of the measured stiffness.


Placental amino acid uptake. IV. Transport microvillous membrane vesicles. The recent characterization of a vesicular microvillous plasma membrane preparation from human placenta has made possible study of the characteristics of amino acid transport by the isolated membrane. Variation of medium osmolality demonstrated that alpha-aminoisobutyric acid (AIB) is taken up virtually entirely into a vesicular space. Vesicular volume was determined from equilibrium uptake of three dissimilar nonamino acid substrates, all of which gave a common value. Temperature dependence, saturability, specificity, and similarity of kinetic constants all indicated that AIB uptake by the vesicles resembles that by whole villous tissue. AIB uptake was stimulated specifically by an inward sodium gradient and unaffected by an outward potassium gradient. The persistence of stimulation up to 2 h after the gradient was established could be correlated with the slow equilibration of sodium across the membrane. AIB exodus could be studied with minimal problems of substrate recapture by using preloaded membrane vesicles bound tightly to cellulose ester filters to facilitate transfer to fresh medium. The exodus process was saturable with a Km considerably greater than that for entry.


Binding of 2,3-diphosphoglycerate by spectrin and its effect on oxygen affinity of hemoglobin. The relationships between spectrin, a structural protein of the red blood cell (RBC) membrane facing the cytoplasm, and hemoglobin were studied. The oxygen-binding properties of stripped hemoglobin were not altered by the presence of spectrin, but the interaction of hemoglobin with organic phosphates was reduced by the addition of spectrin. The presence of the enzyme glyceraldehyde 3-phosphate dehydrogenase (G3PD), another component of the RBC membrane used as a control, did not change the oxygen affinity of either stripped hemoglobin or of hemoglobin solutions containing phosphates. Binding studies using the gel filtration method at pH 7.3 indicated reversible binding of 2,3-diphosphoglycerate to spectrin. A unit of 220,000 daltons was calculated to have seven binding sites and a binding constant of 1.2 X 10(4) M-1. A mechanism is proposed in which spectrin may facilitate oxygen transport for hemoglobin molecules reaching the membrane.


Controlled bending of high-resistance glass microelectrodes. The short working distance of compound microscope lenses in many cases prevents microelectrode penetrations of cells perpendicular to the cell surface. Bending electrodes very near their tips removes this constraint. A method is described for bending glass microelectrodes with a hot filament while their tips are immersed in a water drop. Immersion protects the fine electrode tips from the heat and provides control over the angle through which the electrodes are bent.


Some characteristics of kidney Na+ -dependent glucose carrier reconstituted into sonicated liposomes. Studies of the Na+-gradient coupled D-glucose carrier of the brush border membrane of rabbit kidney cortex extracted with Triton X-100 and reconstituted into artificial liposomes show that the reconstituted carrier behaves in those respects so far studied in a manner very similar to the same carrier studied in natural membrane vesicles.


Feeding in response to insulin but not to 2-deoxy-D-glucose in the hamster. Adult hamsters did not increase their food intake in response to subcutaneous injection of 2-deoxy-D-glucose (2DG) at doses of 50, 200, 350, 500, 750, 1,000, or 1,500 mg/kg. The failure to feed in response to 2DG was apparent regardless of time of testing and length of test. Hamsters did display marked hyperglycemia after 2DG treatment. Therefore, hamsters do detect and form neural responses to 2DG. In contrast to 2DG, injection of regular insulin, 2, 4, or 8 U/animal, caused hamsters to significantly increase their food intake over a 5-h test period. Furthermore, injection of 4 U of protamine zinc insulin twice daily also caused pronounced increases in food intake and weight gain by hamsters. Because hamsters do not seem to posses a feeding response to 2DG-induced glucoprivation, it seems unlikely that insulin elicits feeding via the glucoprivic control in this species. The results suggest that 1) hamsters lack the glucoprivic control of feeding behavior as exercised by 2DG, 2) 2DG and insulin treatments are not equivalent ingestive challenges, and 3) insulin-induced feeding may result in part from activation of a nonglucoprivic control of food intake.


Fetomaternal transfer of glucose analogues by sheep placenta. The steady-state permeability of the placenta to radiolabeled 3-O-methyl--D-glucopyranose (3MeG), alpha-methyl-D-glucopyranoside (AMG), and D-xylose was measured in chronically catheterized conscious sheep near term. Fetomaternal flux was calculated by application of Fick's principle to the uterine circulation after injection to the fetus. At a fetal glucose concentration of 10.2 +/- 1.25 mM, the permeability of 3MeG was half the maximal value of 59.5 +/- 11.2 ml/min found by extrapolation to zero glucose concentration. The permeability to 3MeG is considerably greater than is compatible with restricted diffusion, which together with the competitive effect of D-glucose suggests a carrier-mediated transfer mechanism. The permeability to AMG was less than 0.1 ml/min. The specificity pattern of sugar transport from the fetal side of the sheep placenta is different from that reported for gut lumen or kidney tubule in other species. D-Xylose is not metabolically inert after its injection into the fetal lamb.


Protein turnover in rat skeletal muscle: effects of hypophysectomy and growth hormone. The role of growth hormone in regulating protein turnover was examined in a perfused preparation of rat skeletal muscle. The perfused muscle maintained in vivo levels of ATP and creatine phosphate and exhibited constant rates of oxygen consumption and protein synthesis. Hypophysectomy reduced the rate of protein synthesis, the concentration of RNA, and the efficiency of protein synthesis in gastrocnemius muscle to 30, 46, and 66 percent of normal, respectively. In vivo treatment of hypophysectomized (hypox) rats with bovine growth hormone (250 microgram/day for 5 days) resulted in small increases in protein synthesis and RNA, whereas synthesis/RNA was returned to near normal. Elevation of ribosomal subunits in psoas muscle indicated an inhibition of peptide-chain initiation in hypox rats that was reversed by in vivo growth hormone treatment. Thus, hypox rats exhibited both a decreased capacity and a decreased efficiency of protein synthesis. Growth hormone replacement primarily increased efficiency of protein synthesis. The rate of protein degradation and the activity of cathepsin D in gastrocnemius muscle were decreased by hypophysectomy. Growth hormone treatment had no significant effect on degradation.


Efffect of vasoactive intestinal polypeptide on gallbladder smooth muscle in vitro. The effect of vasoactive intestinal polypeptide (VIP) on basal and octapeptide of cholecystokinin (OP-CCK) induced tension was examined with guinea pig gallbladder smooth muscle strips in vitro. VIP alone produced dose-related decreases in resting tension and antagonized spontaneous contractile activity where present. In combination with OP-CCK, VIP decreased the expected contractile respone. The degree of antagonism depended upon the concentrations of OP-CCK and VIP. VIP had no effect on acetylcholine-induced contractions. From these observations, we propose that VIP can affect gallbladder motor activity by decreaseing smooth muscle tone and by antagonizing cholecystokinin. These findings lend further support to our proposal that gallbladder motor function may depend upon the action and interaction of the gastrointestinal hormones.


Effect of luminal constituents on vitamin K1 absorption into thoracic duct lymph. Lymphatic appearance rate of [3H] phylloquinone was studied in unanesthetized rats with cannulated bile and lymph ducts. A linear relationship (y= -44.9 + 10.2x, r=0.99) was found between the rate of the compound's infusion into the duodenum and its appearance rate in the lymph. Increasing the taurocholate infusate concentrations from 5 to 15 mM increased phylloquinone appearance rate in the lymph from 6.47 +/- 1.82 to 24.14 +/- 1.20 pmol/min (P less than .01). Varying the infusate pH from 4.35 to 8.0 did not change lymphatic appearance rate of vitamin K1 or lymphatic flow rate. Addition of short-chain fatty acid (butyrate) to the infusate enhanced the total absorption of vitamin K1 into the bile and lymph, whereas the addition of polyunsaturated fatty acids inhibited the total absorption of the vitamin. These experiments delineate some factors that modify the extrusion rate of vitamin K1 out of the enterocyte into the lymphatic circulation and add information regarding this phase of the absorptive pathway of lipids.


Changes in red cell space of bone in hypocalcemic states: studies in rat femur. With the use of technetium-99m-labeled red cells, the red cell space of the femur was found to be increased in rats fed a 0.01 percent Ca diet for 4 wk, at which time they were also hypocalcemic. Rats fed the same diet for 2 wk did not demonstrate hypocalcemia nor hypervascularity of the femur. Thyroparathyroidectomized (TPTX) rats fed the calcium-deficient diet produced hypocalcemia nor hypervascularity as did TPTX rats fed a normal diet for 4 wk. However, bone vascularity was normal at 2 wk post-TPTX (normal diet) when the degree of hypocalcemia was less marked. Inhibition of prostaglandin synthetase with oral indomethacin 0.2 mg/100 g per 12 h for 60 h did not alter the red cell space estimates but did increase bone blood flow in both normal and calcium-deficient animals. Acute restoration of normocalcemia with CaCl2 orally in the calcium-deficient rats did not revert the bone hypervascularity. The evidence suggests that in these models of hypocalcemic states, the rise in the vascular space of bone does not result from the influence of PTH, calcitonin, diet, or prostaglandins.


Effects of some gastrointestinal hormones on two muscle layers of duodenum. The duodenums of opossums and cats were cut into strips 2 mm wide and 2-2.5 cm long. Strips cut in the oral-caudal axis were called longitudinal strips; those cut at 90 degrees to that axis were called circular strips. Cholecystokinin (CCK) and cerulein stimulated phasic contractions of circular muscle of opossum duodenum, but had no effect on the longitudinal muscle. The effect of CCK was not blocked by tetrodotoxin (10(-7)M), indicating a direct muscle stimulation. CCK had no effect of both muscle layers of the cat duodenum. Vasoactive intestinal peptide raised tension in longitudinal muscle, but reduced tension in circular muscle of opossum duodenum. Glucagon slightly reduced tension in both longitudinal and circular muscle of opossum duodenum. It also inhibited contractions of circular muscle caused by acetylcholine. Pentagastrin and secretin had no effect on either muscle layer in either species. These findings suggest that the circular and longitudinal muscle layers of the duodenum respond differently to at least some gastrointestinal hormones. Also, there is species variation in response to gastrointestinal hormones.


Effect of insulin on kinetics of sugar transport in heart muscle. Insulin increased the maximal rate of sugar transport in the perfused rat heart, but had essentially no effect on the Michaelis constant of sugar entry or half-maximal constant for equilibrium exchange. In control hearts, the following kinetic parameters of 3-O-methylglucose transport were measured: Michaelis constant for entry, 7-10 mM; equilibrium exchange constant, 7 mM; and activity constant (Vmax/Km) from 0.02 to 0.1 ml/g.min. In insulin-treated hearts, these values were 6 mM, 3 MM, and 2.2 ml/g.min, respectively. These changes in transport constants were consistent with a model in which 1) sequestered carrier was released by the hormone or 2) carrier movement, in all forms and directions, was accelerated. Measurements of glucose transport in control hearts indicated that the Michaelis constant for entry was 4 mM and the activity constant, 0.5 ml/g.min. In insulin-treated hearts, quantitation of transport parameters was prevented by accumulation of intracellular glucose.


Salivary gland K+ transport: in vivo studies with K+-specific microelectrodes. Stimulation-induced transport of K+ in the submandibular salivary gland of cats and dogs anesthetized with pentobarbital was studied with an extracellular K+-specific microelectrode. Electrical stimulation of the para-sympathetic chorda-lingual nerve caused a rapid transient increase in extracellular K+ concentration from 2.2 to 18.7 meq/liter in the cat and from 2.3 to 15.2 meq/liter in the dog. Eventually the K+ concentration fell below the prestimulatory level, indicating uptake of K+ by the gland cells. In case of prolonged stimulation (2-10 min), the uptake began during stimulation. However, a further reduction in extracellular K+ concentration occurred upon cessation of stimulation, a result that demonstrated that the cells did not fully recover their K+ ,content during stimulation. The latency of the release of K+, defined as the time from the beginning of stimulation to the point at which, the K+-specific microelectrode signal had increased by 2 mV, was 0.6 s in the cat and 0.8 s in the dog. Because these are overestimates of the "true" latencies, we conclude that the K+ release begins simultaneously with the hyperpolarization of the acinar cell membrane.


Experimental validation of measurements of glucose turnover in nonsteady state. The aim of the present experiments is to validate, in conscious dogs, the tracer infusion methods of measuring nonsteady turnover rates. This was done in nine experiments performed in four normal dogs by infusing isotopically labeled glucose (2-3H, 6-3H, 1-14C) and monitoring the concentrations of both the labeled and unlabeled substances. The validation is based on the observation that a high exogenous infusion of glucose will suppress endogenous glucose production and become the sole source of glucose in the body. By infusing glucose at a high, time-varying rate, calculating its rate of appearance, (Ra) and comparing it to the infused rate, the method can be verified. The calculations were based on: a) a single-compartment model with a modified volume of distribution; b) a two-compartment model; and c) a generalized dispersion model. The absolute values of the areas of the deviations of the calculated from the infused curves were found to be, respectively, 9.5, 8.4, and 7.8 percent of the total area under the infused curve. It was concluded that the tracer infusion method can reliably measure Ra of glucose when it is changing rapidly, and the system is out of steady state.


A comparison of body fat determined by underwater weighing and volume displacement. Two hydrostatic techniques, underwater weighing and water displacement, were used to determine body fat for 67 volunteer men between 25 and 61 yr of age (-/x=41 yr). All tests were administered in random order in the morning on the same day while subjects were in the postabsorptive state. Test-retest reliabilities for the underwater weighing and water displacement techniques were 0.995 and 0.96, respectively. The correlation between the two hydrostatic techniques was r=0.96. The mean percent fat determined by underwater weighing (-/x=20.1 +/- 6.4) and water displacement (-/x=19.4 +/- 6.1) were significantly different (t=28.16; df=65; P less than 0.001). These analyses showed that both techniques were reliable in measuring percent body fat, but produced slight systematic differences. Regression equations were provided to adjust for the difference.


The sodium transport pool.

The sodium transport pool. The sodium transport pool in epithelial cells represents sodium involved in active transport across the epithelium. There has been much controversy about the size of such a pool and even about its existence. Techniques for estimating the size of this pool are described. By analysis of toad bladder epithelial cells scraped from hemibladders mounted in chambers under a variety of conditions it has proved possible to detect and to quantify a sodium transport pool. Only about 20 percent of non-inulin space sodium measured flame photometrically is contained in this pool. This represents the total sodium entering cells from the mucosal medium, is in good agreement with the cellular sodium measured by the electron microprobe, and averages some 10-16 mmol/kg tissue H2O. Measurements of the pool in other tissues are considered.


Effects of sodium and potassium salts with anions other than chloride on renin secretion in the dog. Intrarenal arterial infusions of sodium and potassium salts with anions other than chloride were given to evaluate the role of the chloride ion in influencing renin secretion (RS). The studies were conducted in dogs with thoracic caval constriction. Sodium lactate increased renal venous plasma sodium concentration (RVPNa) from 142 to 166 meq/liter (n, 6); RS decreased from 3,070 to 1,510 ng angiotensin/min (P less than 0.005). Arterial blood pressure and renal blood flow were not changed appreciably. Sodium excretion (ENa) increased, whereas chloride excretion (EC1) fell during the first three 15-min infusion periods. Potassium lactate increased renal venous plasma potassium concentration from 4.1 to 6.2 meq/liter (N, b). RS decreased during the first three 15-min periods of infusion (from 3,470 to 2,180 ng angiotensin/min, P less than 0.01). ENa and EC1 increased during the infusion. Potassium sulfate also decreased RS, and EC1 was usually increased. The results with sodium lactate favor a role for sodium compared with chloride in mediating the decreased renin release, but there are other possible interpretations which have been discussed. Additional studies are needed to resolve the role of chloride during potassium infusion.


Vasopressin responsiveness of renal adenylate cyclase in newborn rats and rabbits. Newborns show an inability to concentrate maximally their urine. The vasopressin responsiveness of adenylate cyclase was, therefore, examined in membranes obtained from kidneys of neonatal and adult rats and from renal medulla and isolated collecting tubules of newborn and adult rabbits. In spite of higher basal and NaF-stimulated activity, vasopressin failed to stimulate adenylate cyclase from neonatal rat kidneys. In neonatal and adult rabbits, basal and NaF-stimulated adenylate cyclase activities of renal medullary membranes were comparable but vasopressin stimulation was significantly lower in the newborns. No change in hormonal activation constant was observed. This hyporesponsiveness of neonatal adenylate cyclase to vasopressin was confirmed with single isolated rabbit collecting tubules for adenylate cyclase determination, a highly sensitive preparation. It is intriguing to speculate that the low vasopressin stimulation of the medullary adenylate cyclase in the developing kidney may contribute to the known limitations of the urinary concentrating mechanism in the newborn period.


Aldosterone in the exaggerated natriuresis of spontaneously hypertensive rats. The effect of mineralocorticoid hormones on the urinary responses of spontaneously hypertensive and normotensive rats to oral salt loading was determined. In response to a control salt load, the increase was determined. In response to a control salt load, the increase in urinary sodium excretion by the spontaneously hypertensive rats was significantly greater than that of the normotensive rats [48 +/- 6 (SE) mueq/h vs. 26 +/- 4 mueq/h]. Treatment with spironolactone did not significantly alter the natriuretic response of the spontaneously hypertensive rats (43 +/- 8 mueq/h) to another salt load, but increased the natriuretic response of the normotensive rats (55 +/- 7 mueq/h) to that of the hypertensive rats. D-Aldosterone suppressed the natriuretic response to salt loading of the hypertensive rats to a level which was not significantly different from that of the normotensive rats. Plasma aldosterone concentration was significantly lower in the spontaneously hypertensive rats than in the normotensive rats (18.0 +/- 3.3 and 52.1 +/- 5.2 ng/100 ml, respectively). Neither extracellular fluid volume nor total body water in spontaneously hypertensive and normotensive rats were significantly different. The data support the hypothesis that the exaggerated natriuresis in the spontaneously hypertensive rats is mediated by a relative lack by these rats of aldosterone-mediated distal tubular sodium reabsorption.


Site of formation of kinins in the dog nephron. The site of formation of kinins in the nephron was determined by stop-flow studies in dogs. Klinin, inulin, sodium, potassium concentrations were measured in the fractions collected during the stop-flow procedures. In addition, in three of the 17 stop-flow experiments, kallikrein activity was also measured. The highest kinin concentration after correction for water reabsorption was found in the fractions that were probably trapped in the distal part of the nephron. Either one or two peak was located either in the fraction overlapping (in one instance) or in the fractions coming prior to the fractions with the highest concentration of potassium. This first peak was present in all but one of the stop-flow experiments and was greater than the second peak. The second peak of kinins was found in 13 of the 17 stop-flow exeriments and was located in the fractions with the lowest sodium concentration. Those fractions with the lowest sodium concentration. Those fractions with the lowest sodium concentration also had the highest kallikrein concentration. No evidence of kinin formation was found in the fractions representing the proximal nephron. We conclude, therefore, that kinins are formed in the distal part of the nephron, with the highest concentration found in the last part of the distal nephron and/or in the renal papilla and pelvis.


Physical properties of isolated perfused basement membranes from rabbit loop of Henle. Isolated, perfused segments of late proximal straight tubule, descending thin limb of Henle, and ascending thick limb of Henle from the rabbit were studied before and after removal of the epithelium with sodium deoxycholate. The relationship between transmural hydrostatic pressure and outer tubule diameter was similar in paired intact tubules and basement membranes, indicating that basement membrane is the principal determinent of tubule distensibility. As calculated from teh measured perfusate flow at several different transmembrane hydrostatic pressures, the hydraulic conductivity of the basement membranes was 6-8 X 10(-3) cm3/cm2.min.cmH2O. With use of these LP values and the calculated oncotic pressure required experimentally to reduce transmembrane hydrostatic pressure transiently to zero, the apparent reflection coefficient of the basement membranes for serum albumin was estimated to be 0.05-0.16. It is concluded that basement membranes of the loop and of other previously studied segments of rabbit nephron provide very strong and elastic mechanical support to the epithelium while having minimal resistance to flow of water and of solutes as large as serum albumin.


Fluid absorption with and without sodium in isolated perfused snake proximal tubules. Net fluid absorption (JV) was studied in isolated, perfused snake (Thamnophis spp.) proximal renal tubules. With standard (150 mmol/liter Na+) bicarbonate-buffered Ringer in perfusate and standard Ringer plus dextran (4 g/100 ml) in bath, JV was about 0.9 nl min-1 mm-1. Removing dextran from bath reduced JV by about 20 percent. When sodium in perfusate was replaced with choline JV approached zero. However, when sodium in bath as well as perfusate was replaced with choline, JV returned to control level. Results were the same when sodium was replaced with tetramethyl-ammonium, sodium chloride was replaced with sucrose or lactose, or chloride was replaced with methyl sulfate. In contrast, replacing sodium in perfusate or in both perfusate and bath with lithium did not reduce JV. Fluid absorption was always isosmotic. Replacing bicarbonate with phosphate or Tris in sodium-containing media had no effect on JV, but the presence of buffer in sodium-free or low-chloride media may have been important for JV. Reducing temperature 10 degrees C reduced JV by about 35 percent with either sodium chloride or sucrose in both perfusate and bath. The results indicate that isosmotic fluid absorption can occur when lithium is substituted for sodium or when some other substitution is made for sodium, chloride, or both in perfusate and bath simultaneously.


Cardiac output and renal excretion rates during acute blood volume expansion in rats. Selected central vascular parameters and renal excretion rates were monitored in anesthetized rats after acute, isohemic blood volume expansion by 33 percent. The infusate was an equilibrated mixture of animals' own blood and isotonic, isoncotic (6 percent) bovine albumin. Expansion increased mean arterial pressure by 35 percent, mean central venous pressure (CVP) by 850 percent, cardiac output (CO) by 56 percent, hematocrit (Hct) by 25 percent, plasma protein concentration (Ppr) by 25 percent, renal excretion rates of volume by 4,400 percent, of sodium by 2,800 percent, and of potassium by 360 percent of the respective preinfusion value. Hct and Ppr measurements suggested that 15 min after the end of the infusion, only 33 percent of infused volume remained within the circulation and that there was little further change in this during the remainder of the experiment. At the end of the elevated renal response, CVP and CO alone had returned to control values. Renal excretion rates were highly correlated with CO, but they were delayed by 2-5 min with respect to it. The results suggest that the renal response to acute volume expansion does not primarily control blood volume. Cardiac output may be the controlled variable in the response.


Autoregulation of cerebral blood flow during early experimental renal hypertension in the conscious dog. Using the radioactive microsphere technique, cerebral blood flow (CBF) was measured in six conscious dogs before intervention and again on the 3rd-5th days after inducing hypertension by the one-kidney Goldblatt (1-KGH) procedure. Sham-operated controls were also studied. The normal temporal variability of CBF, as well as the precision of the microsphere technique in measuring CBF were also determined in other normal dogs. A left atrial catheter was used for the microsphere injections (15 micrometer diam spheres) and an aortic catheter was used for cardiac output and blood pressure measurements. On the 3rd-5th days after 1-KGH, mean aortic pressure increased from a control value of 94 +/- 7 mmHg to 135 +/- 20 mmHg (P less than 0.005). CBF did not change significantly from the control flow of 57.1 +/- 7.9 ml/100 g per min. Calculated cerebral vascular resistance increased by 47 percent (P less than 0.025) above the control value. Hence, the early phase of experimental renal hypertension is associated with adequate autoregulation of cerebral blood flow.


Role of extravascular protein in capillary-tissue fluid exchange. A mathematical model of capillary-tissue fluid exchange is presented. The effect of variation in plasma and interstitial osmotic pressure that occurs as a result of convection and diffusion of protein is examined. Analytic solutions to the resulting equations are obtained by using the methods of perturbation theory. It is found that fluid exchange can significantly alter the pericapillary interstitial osmotic pressure, reducing both filtration and reabsorption. Variation in plasma osmotic pressure is important only for certain pathological conditions in which excessive filtration occurs. Specific numerical examples are presented which show quantitatively the extent of these effects for various normal and pathological conditions of physiological interest.


Measurement of local cerebral blood flow with iodo [14C] antipyrine. The autoradiographic diffusible tracer technique for the measurement of local cerebral blood flow was originally designed for use with the radioactive, inert gas 131I-labeled trifluoroiodomethane and is applicable only with tracers that exhibit unrestricted diffusion through the blood-brain barrier. Because of the technical problems associated with the use of gaseous tracers, a suitable nonvolatile tracer has been sought. [14C] Antipyrine has been used previously and found to be unsuitable because of limitations in its diffusion through the blood-brain barrier. An analogue of [14C]antipyrine, iodo [14C]antipyrine, exhibits higher partition coefficients than [14C]antipyrine between nonpolar solvents and water and might, therefore, be expected to diffuse more freely through the barrier. Its use as the tracer in the local blood flow technique leads to values considerably above those obtained with [14C]antipyrine in the rat and cat and essentially the same as those obtained with the gas trifluoro[131I]iodomethane in the cat. Iodo[14C]antipyrine appears, therefore, to be a satisfactory nonvolatile tracer for the measurement of local cerebral blood flow.


Hemodynamic similarities between the trigeminal and aortic vasodepressor responses. The hemodynamic changes associated with hypotension elicited by electrical stimulation of the spinal trigeminal complex (trigeminal depressor response, TDR) or the aortic nerve (aortic depressor reflex, ADR) were compared in rabbits anesthetized with urethan. The hypotension associated with each response was accompanied by bradycardia, a marked fall in total peripheral resistance, a small decrease in cardiac output, and a nonuniform decrease in regional vascular resistances, with the order of magnitude of the decrease being femoral greater than mesenteric greater than renal arterial resistance. In individual experiments the percent decrease in heart rate, total peripheral resistance, or regional resistances was plotted against the percent fall in arterial pressure to obtain a pair of regression lines during the TDR and ADR. There was no significant difference in the slope or y-intercept of the regression line between the TDR and ADR for all of the hemodynamic variables examined. In both responses, however, the slope of the femoral resistance/arterial pressure relationship was significantly greater than that of the renal resistance/arterial pressure relationship. We conclude that the TDR is characterized by a pattern of hemodynamic changes similar to that of the ADR.


Vascular capacitance of dog intestine using mean transit time of indicator. Changes in vascular volume of dog jejunum caused by norepinephrine, isoproterenol, or acetylcholine at constant=flow perfusion, were compared to changes in volume caused by changes in blood flow or venous pressure. Vascular volume was measured by indicator dilution mean transit time, using a step input of indocyanine green (125 microgram/min). Venous pressure was held at 10 mmHg; control arterial pressure was about 110 mmHg. At a control flow of 521 ml/min.kg of tissue, the vascular volume was 104 +/- 14 (SD) ml/kg of tissue. Reducing flow by 75 percent caused the volume to decrease by 29 percent (--31 ml/kg); maximal norepinephrine infusion at constant flow and venous pressure decreased the vascular volume by 24 percent, and a 10-mmHg reduction in venous outflow pressure caused a 25 percent (--27 ml/kg) reduction. On the other hand, isoproterenol (100 microgram/liter) at constant flow caused a 245 percent increase in conductance and only a 12 percent increase in vascular volume. Thus, active venoconstriction, changes in venous pressure, or changes in flow independently may cause changes in vascular volume of the intestine. Active smooth muscle changes in the venous capacitance vessels are not necessarily correlated with changes in the arterial resistance vessels.


Restoration of hemorrhaged plasma volume by gastrointestinal fluid in the dog. Conscious, intact and splenectomized, male dogs were hemorrhaged 35 percent of their blood volumes (23 +/- 3 and 25 +/- 4 ml/kg, respectively) from carotid loop cannulas. Isotonic saline or glucose solutions were administered by gastric tube in volumes equal to the blood volume hemorrhaged. Plasma volume, mean arterial blood pressure, venous hematocrit, plasma protein concentration, and interstitial fluid pressure were monitored after hemorrhage and after fluid treatment. The magnitudes of plasma volume restoration 8 h after hemorrhage in the nontreated dogs averaged 56 +/- 9 percent of the hemorrhaged volume and did not differ significantly between intact and splenectomized dogs. Plasma volumes, however, were increased significantly by enterally administered fluids. The maximum rates of plasma volume restoration occurred within the 1st h after fluid treatment. Approximately 46 percent and 28 percent of the hemorrhaged plasma volume was replaced by saline and glucose solutions, respectively, during this period. Results support the hypothesis that fluid is absorbed from the gastrointestinal tract following hemorrhage, and that enterally administered fluids restore plasma volume at a rate and to an extent exceeding that provided by net interstitial fluid exchange alone.


Kinetic analysis of calcium desaturation curves from isolated kidney cells. This paper provides mathematical solutions for calculating calcium fluxes and compartments in isolated kidney cells from calcium-45 desaturation curves. In contrast to other available methods, these solutions allow the calculation of kinetic parameters even if isotopic equilibrium has not been reached at the beginning of the desaturation period. To test the validity of the method, calcium-45 desaturation experiments were performed in isolated kidney cells after labeling periods of 30, 60, 90, or 120 min. Even though the calcium-45 desaturation curves differ with different labeling times, the respective values of the calculated parameters are practically identical. The optical labeling period was found to lie between 60 and 120 min. Since this new method does not require initial isotopic steady state, it allows a formal kinetic analysis of tracer desaturation curves even after short periods of labeling.


A field and circuit thermodynamics for integrative physiology. II. Power and communicational spectroscopy in biology. This paper continues the development begun in Part I (15), to show in what way it is meaningful to reduce biological phenomena to physical theory at any level of organization. The appropriate level-independent physics is comprised of thermostatics, thermodynamics of irreversible processes, statistical mechanics, and nonlinear mechanics. Generalized, these approaches lead to a spectroscopic description of the constellation of periodic processes that constitute the living states. The spectroscopic description is here applied also to the inputs received by living systems, from lethal, high-energy, nuclear particles and radiation to low-energy communicational signals that make up languages understandable at the various levels in an hierarchical system. The concept of language is then itself generalized, showing how the empirical relation discovered by Zipf can be derived from a thermodynamic basis. It is demonstrated that certain linguistic and statistical-mechanical distribution functions can be related. Applications of the field thermodynamic approach to two problems in transport phenomena are given in APPENDIX I; applications of field thermodynamics to language and communication are given in APPENDIX II.


Studies of calcium-45 desaturation from kidney slices in flow-through chambers. This paper describes a method to measure calcium fluxes and calcium exchangeable pools in tissue slices by continuous perifusion in flow-through chambers. 45Ca desaturation from rat kidney slices can be analyzed as in an open three-compartment catenary system. A set of equations is given to calculate all the relevant kinetic parameters from the triple exponential equations which best fit the desaturation curves. The results show that the kinetic parameters obtained in kidney slices by this new method are in the same order of magnitude as those previously observed in cultured monkey kidney cells.


Comparative aspects of brain barrier systems for nonelectrolytes. Blood-brain and blood-CSF barriers to inulin were compared in 11 vertebrate species. Twenty hours after systemic administration, [14C]inulin penetrated into the central nervous system to an equivalent extent in mudpuppy, salamander (adult and larval), red sculpin, big skate, little skate, southern stingray, and Atlantic stingray with values for RB (dpm/g brain divided by dpm/ml plasma) in the range 0.01- 0.04 and for RCSF (dpm/ml CSF divided by dpm/ml plasma) from 0.02 to 0.04. These values are similar to those reported for mammals. For dogfish, nurse shark, and lemon shark, RB ranged from 0.04 to 0.09 and RCSF from 0.08 to 0.29 and for hagfish RB=0.12, indicating that barrier systems to inulin are poorly developed in sharks and possibly absent in hagfish. Analyses of radiolabeled urea and sucrose penetration into brain and CSF revealed further differences in shark barrier function. Brain barriers to insulin in dogfish and little skate developed with age; in nurse shark there was no detectable change in the inulin ratios over the weight range, 0.2-110 kg.


Adrenergic modulation of insulin secretion in vivo dependent on thyroid states. Insulin secretory responses via adrenergic mechanisms were studied in vivo with hyperthyroid rats prepared by daily injections with thyroxine and with rats rendered hypothyroid by the addition of methylthiouracil in the drinking water. Isoproterenol, a beta-adrenergic agent, caused hyperinsulinemia in hyperthyroid rats more markedly than in euthyroid rats, but failed to induce hyperinsulinemia in hypothyroid rats. The isoproterenol-induced hyperinsulinemia was abolished by a beta-adrenergic receptor blocker in hyperthyroid as well as in euthyroid rats. The glucose-induced hyperinsulinemia was enhanced in hyperthyroid, was not essentially affected in euthyroid, and was inhibited in hypothyroid rats, by an alpha- and beta-adrenergic agent such as epinephrine. It is concluded that the relative function of alpha- to beta-adrenergic receptors responsible for the pancreatic secretion of insulin is dependent on the thyroid state; beta-adrenergic actions are predominant over alpha-actions in hyperthyroidism and vice versa in hypothyroidism.


Glucose transport in isolated rat adipocytes with measurements of L-arabinose uptake. Data is presented suggesting that rates of L-arabinose transport, calculated from L-[1-14C]arabinose uptake measurements, can be used as indicators of changes in the rates of glucose transport in isolated rat adipocytes. L-[1-14C]arabinose, at 37 degrees C, was found to be nonmetabolizable and taken up by adipocytes exponentially with time reaching 95% of equilibrium in 30 min. When L-arabinose is corrected for background, the corrected uptake values conform to the time-dependent monoexponential uptake relationshiop predicted for a facilitated transport system and are not significantly different from 0 in the presence of 70 micron cytochalasin B. Transport rates were calculated from corrected uptake values near the half-maximal uptake of L-arabinose and from a value of the total amount of L-arabinose in the cell at equilibrium. Competitive inhibition of L-arabinose transport by glucose and countertransport of L-arabinose in the presence of glucose suggest that L-arabinose and glucose share the same transport system. Data is presented demonstrating the effect of insulin and dexamethasone on the transport system that confirms the conclusions obtained by other investigators using other methods.


Erythritol and mannitol clearances with taurocholate and secretin-induced cholereses. The biliary clearances of [14C]erythritol (Cery) and [3H]mannitol (Cmann) were measured simultaneously in dogs during cholereses induced by sodium taurocholate and by secretin. Cery increased equally with the increase in bile flow induced by taurocholate, whereas mannitol entry into bile was partially restricted; deltaCery/deltabile flow averaged 0.96; deltaCmann/deltaCery averaged 0.81. Values for erythritol clearance exceeded bile flow by a constant volume over a wide range of bile flows, a result that suggests distal reabsorption of a fixed amount of fluid, independent of canalicular bile production. During secretin-induced choleresis both Cery and Cmann accompanied 30-40% of the increase in bile flow, and the ratio of Cmann/Cery was 1.02. Thus the secretin-responsive region is permeable to both erythritol and mannitol. This affects the extent to which measured erythritol clearance accurately reflects canalicular bile formation; Cery may underestimate or overestimate canalicular bile flow. The electrolyte composition of bile remained relatively constant over a broad range of bile flows although the characteristics of taurocholate- and secretin-induced biles differed from each other. Taurocholate-stimulated bile was virtually isotonic. Secretin-induced bile had a high total concentration of electrolyte (mean concentration 367 meq/liter) rich in chloride and bicarbonate and was hypertonic.


Dietary iodine and accumulation of radioiodine in thyroids of chickens. Groups of hatchling white leghorn cockerels were fed a basic, semisynthetic low-iodine diet to which various amounts of iodide were added: 0 up to 100 microgram I/g feed. Growth rates were unaffected by the range of dietary iodine content. A transitory goiter occurred only in the group fed the basic low-I diet. Half-life of 131I in the thyroid increased directly and fractional turnover rate inversely with increase of dietary iodine. Trichloroacetic acid-soluble iodine in serum did not accurately reflect variation of dietary iodine. However, effective clearance and binding rate constants did decrease proportionally to dietary iodine increase beyond the first 3-5 days. Concentration of iodine in thyroid was directly proportional to dietary iodine after 10 days. There was no consistent correlation between thyroxine or triiodothyronine and dietary iodine except in general terms of high and low dietary iodine groups. The avian thyroid exhibits great lability in adjusting functionally to a wide range of dietary iodine contents.


Dietary iodine and thyroidal iodide transport in chickens: organic binding blocked. Experimental data concerning the increase in T/S [I-] (ratio of concentration of radioiodide in thyroid to that in serum) during equilibration after a single injection of radioidide were obtained from chickens in which protein binding of radioidide was inhibted by methimazole. Equilibration data were obtained from chickens fed a low-iodine diet (2 mo) as well as the low-iodine diet to which various amounts of NaI had been added. Experimental data were compared with productions based on the open two-compartmental model of Wollman and Reed (Am. J. Physiol. 196: 113-120, 1959). Thyroidal clearance (C/m) of radioiodide (the rate at which radioiodide is transferred from blood into the thyroid and equal to the radioiodide content of C microliter serum per minute) varied inversely to iodine content of feed. Exit rate constant (KTB, the fraction of thyroidal radioiodide transferred to serum per minute) was relatively more constant. The experimental data fitted the predictions from the model within experimental error. Thirty days of feeding the low-iodine diet was required before C/m stabilized at 50 microliter/min per mg and KTB at 0.065; stabilization of C/m and KTB occurred in 12 days with the highest iodine diet.


Primary role of decreased fatty acid synthesis in insulin resistance of large rat adipocytes. The ability of large fat cells from spontaneously obese rats to synthesize fatty acids from D-[1-14C]glucose, D-[6-14C]glucose, or [2-14C]pyruvate was markedly diminished compared to small fat cells from lean animals. Furthermore, fatty acid synthetase and acetyl coenzyme A carboxylase activities in dialyzed homogenates of large fat cells were inhibited by 84 and 90%, respectively, compared to small cells. Pentose shunt activity, but not glycolytic flux, was also markedly inhibited in large fat cells incubated with or without insulin. However, the NADPH oxidant vitamin K5 completely restored pentose shunt activity in large cells to the elevated levels observed in small fat cells in the presence of this agent or insulin. Furthermore, inhibition of mitochondrial oxidation and fatty acid synthesis in small cells by rotenone led to a secondary inhibition of pentose shunt activity indicating a link between these two pathways. Direct measurements of glucose-6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase activities in fat cell homogenates showed no difference between cell types. The data provide strong support for the hypothesis that the fatty acid synthetic pathway is the primary metabolic defect in large insulin-resistant rat adipocytes, a defect which secondarily leads to inhibited pentose shunt activity.


Glutamine metabolism, interorgan transport and glucogenicity in the sheep. [U-14C]glutamine and [6-3H]glucose were infused into four groups of sheep: fed, NH4Cl acidotic, fasted, and dexamethasone treated. Net and unidirectional plasma glutamine fluxes in the portal-drained viscera (PDV), liver, kidneys, and hindquarters were measured by multiplying venoarterial concentration differences and 14C extraction ratios by the rate of blood flow. In fed sheep, glutamine was released by kidneys and muscle but removed by PDV and liver. In all other sheep, renal glutamine release either decreased or switched over to net removal largely due to increased unidirectional renal utilization. This increased renal glutamine demand was compensated for, during acidosis, by a decreased net hepatic glutamine removal but, during fasting and dexamethasone treatment, by an increased muscle glutamine release. Plasma glutamine and glucose turnover rates averaged 11-12 and 19-24 mmol/h but the percentage of glutamine converted to glucose was higher during fasting and dexamethasone treatment (21%) than in normal fed sheep (17%) perhaps reflecting the increased glutamine removal by the kidneys. Since renal glutamine utilization increases with acidosis and fasting and, since glutamine turnover remains unchanged, glutamine metabolism by other body tissues must be altered to compensate for renal changes.


Extrapancreatic glucagon in control of glucose turnover in depancreatized dogs. Depancreatized dogs have plasma immunoreactive glucagon (IRG), which is of gastric origin and is immunologically indistinguishable from pancreatic glucagon. The effects of extrapancreatic IRG on the tracer-determined rate of glucose production were examined to establish whether this hormone contributes to the hyperglycemia observed in six conscious, depancreatized dogs after insulin withdrawal. The dogs were initially maintained normoglycemic with an intraportal insulin infusion. Insulin withdrawal resulted in a 53 and 70% decrease of serum immunoreactive insulin (IRI) at 60 and 210 min, respectively. At 60 min, plasma glucose rose and Ra increased by 50%. A somatostatin-induced decrease in IRG prevented a further increase in Ra and glucose; after somatostatin withdrawal, IRG, Ra, and plasma glucose increased. Arginine given 1 or 3 h after insulin withdrawal increased IRG by 100 pg/ml, and mean Ra rose by 8.9 mg/kg-min. Thus, in depancreatized dogs with low but detectable serum IRI, IRG suppression is associated with inhibition of Ra and further rise in plasma glucose is prevented. Stimulation of IRG release increases Ra and results in marked hyperglycemia. It is concluded that extrapancreatic glucagon has a diabetogenic effect during acute insulin defiency.


Role of prostaglandin E2 in zinc absorption in the rat. The supernatant of cytoplasmic extract of rat small intestine was mixed with 65Zn and subjected to Sephadex G-75 column chromatography. The activity of 65Zn was detected in four peaks with estimated 800, 10,000, 50,000-75,000 mol wt, and larger than 100,000 daltons. The zinc-binding ligand from the 800 mol wt peak was prostaglandin or prostaglandin-like as indicated by ultra-violet absorption spectrum, by absorption spectrum shift in alcoholic potassium hydroxide, by its effects on pulmonary vascular resistance, and by radioimmunoassay. Addition of prostaglandin E2 or prostaglandin extracted from rat small intestine with ethyl acetate into the lumen of intestinal sacs resulted in a two to threefold increase in the activity of 65Zn in the external medium after 15-20 min incubation. The absorption and tissue distribution of orally administered 65Zn were decreased by 60% in indomethacin-treated rats and increased 70% when ethyl acetate-extracted prostaglandin and radioactive zinc were given simultaneously. These data suggest that prostaglandin not only binds zinc, but also facilitates its transport across the intestinal mucosa.


Effects of prolonged vasopressin treatment in Brattleboro rats with diabetes insipidus. Normal Long-Evans rats (LE) exhibited diurnal variations of plasma arginine vasopressin (AVP) concentrations with peak values at 10 A.M. and minimum values at 1 P.M. Brattleboro rats heterozygous for hypothalamic diabetes insipidus (DI) had significantly reduced plasma AVP concentrations and increased plasma osmolalities when compared with LE rats. By prolonged injection of 100 mU/day of vasopressin tannate (VPT) into Brattleboro rats homozygous for DI, plasma AVP concentrations close to those of LE rats were achieved. Potassium was retained for 7 days until escape of vasopressin-induced potassium retention occurred. When 500 mU VPT were injected into DI rats, high plasma AVP levels were induced. Potassium was retained for 2-3 days. After initial sodium retention, periods of natriuresis occurred. During treatment with 100 mU VPT/day most of the alterations present in DI rats were corrected, which included increased water turnover and external water loss, increased hematocrit and plasma sodium concentrations (but not increased plasma osmolalities), hypokalemia, increased activity of the renin-angiotensin system, and reduced adrenocortical function.


Effects of chronic tubular obstruction in Necturus kidney. The effects of chronic single nephron or mesonephric duct obstruction on renal pressures were measured in anesthetized Necturi by servo-null techniques. Glomerular capillary hydrostatic pressure (PGC) averaged 11.3 +/- 1.2 (SD) cmH2O in 18 normal nephrons. Chronic tubule blockade for 2-6 days produced no significant change in PGC. Light and electron microscopy of the juxtaglomerular apparatus (JGA) revealed juxtaglomerular cell granules widely dispersed along the course of preglomerular arterioles, a deficient macula densa, and no polkissen. The absence of a detectable change in PGC with chronic tubule blockade, i.e., a tubuloglomerular feedback response, may reflect poor development of the JGA in this amphibian.


Renal and adrenal responses to [des-Asp1]angiotensin I in the dog. There is evidence for the endogenous generation of [des-Asp1]angiotensin II (AIII) from a nonapeptide precursor, [des-Asp1]angiotensin I ([des-Asp1]AI). In the present study, the effects of equipressor doses of exogeneously administered [des-Asp1]AI and AIII on renal function and plasma aldosterone concentration were compared. Intravenous infusion of [des-Asp1]AI (75 ng/kg min-1 for 40 min) decreased renin secretion, renal blood flow, creatinine clearance, and sodium and potassium excretion in dogs. Infusion of AIII at one-third of the rate of [des-Asp1]AI (25 ng/kg min-1) produced comparable decreases in these same parameters. Filtration fraction was increased with both peptides. Both peptides also increased plasma aldosterone concentration to the same extent. A bolus injection (5 mg i.v.) of the converting enzyme inhibitor SQ 20,881 completely reversed the mean arterial pressure and renal blood flow responses to [des-Asp1]AI, but did not alter these responses to AIII. These data are consistent with the concept that endogenous generation of AIII from [des-Asp1]AI can occur via the action of converting enzyme on this substance.


Localization of central sites of action of angiotensin II on ADH release in vitro. It is now thought that angiotensin II can stimulate antidiuretic hormone (ADH) release in vivo by a direct action in the central nervous system but it is not known whether the locus of stimulation is the hypothalamus or the neurohypophysis or both. Isolated rat neural lobes incubated for 10 min in buffer containing angiotensin II (200 ng/ml or 2 microgram/ml) did not increase ADH release compared to control values, but addition of KCl (60 mM) to the bath markedly stimulated ADH release. However, intact hypothalamoneurohypophysial systems (containing the supraoptic nuclei) incubated with angiotensin II (200 ng/ml or 2 microgram/ml) did show a pronounced stimulation of ADH release. The data support the hypothesis that angiotensin II, at least in vitro, has a central effect on ADH release which is at the level of the hypothalamus.


Bicarbonate absorption by rabbit cortical collecting tubules in vitro. The rate of transport of bicarbonate was studied in isolated perfused rabbit cortical collecting tubules that were absorbing bicarbonate in vitro. Acetazolamide completely inhibited bicarbonate absorption, as was previously observed with isolated proximal tubules. Therefore, carbonic anhydrase probably is important for bicarbonate absorption in both the proximal tubules and collecting tubules. Inhibition of sodium transport by ouabain or elimination of its transport by completely removing the sodium did not cause a decrease in bicarbonate absorption by the collecting tubules. We previously found that inhibition of sodium transport caused a great decrease in bicarbonate absorption by proximal tubules. Therefore, absorption of bicarbonate is not directly related to sodium transport in collecting tubules, but it probably is related to sodium transport in isolated perfused rabbit proximal tubules. Amiloride inhibited bicarbonate absorption by the collecting tubules consistent with previous observations that the drug inhibits urinary acidification. Although amiloride also inhibits sodium transport and reduces the transepithelial voltage across the collecting tubules, the effect of the drug on bicarbonate transport apparently is independent of the other effects.


Tubular sites of potassium regulation in the normal and uninephrectomized rat. Tubular handling of potassium was studied in the Charles River CD (cesarean derived) rat by clearance, micropuncture, and anatomic techniques. The following groups were evaluated: group I, hydropenia; group II, KCl-mannitol infusion; group III, 10% body wt saline loading; group IV, uninephrectomy, hydropenia; and group V, uninephrectomy, saline loading. Comparison of micropuncture samples from early and late distal collection sites (LDCS) and urine collections revealed no net K transport along the distal convoluted tubule in groups I and III-V but net addition of K in all groups beyond the LDCS. Absolute K secretion beyond the LDCS appeared to be flow dependent in groups I-III. The LDCS was noted by light and electron microscopy always to be lined with collecting tubule epithelium. We conclude that no net change in potassium transport occurs along the superficial distal convoluted tubule during hydropenia or saline loading in normal or uninephrectomized Charles River CD rats, but secretion is demonstrable during KCl infusion. Net addition of potassium beyond the LDCS was noted in all groups and this addition was enhanced by uninephrectomy.


Filtration rate and stop-flow pressure feedback responses to nephron perfusion in the dog. Experiments were performed to evaluate the influence of the distal tubular feedback mechanism on glomerular function in the dog. Single nephron glomerular filtration rate (SNGFR) and stop-flow pressure (SFP) were measured from early segments of proximal tubules during alterations in distal perfusion rate (via a late proximal puncture site) and perfusate composition. Perfusion rate (PR) was varied from 16 to 68 nl/min with a microperfusion pump. The intermediate segment of the nephron was blocked with a solid wax cast, thus preventing retrograde influences of the microperfusion procedure. During perfusion with an ultrafiltrate of plasma and an artificial tubular fluid solution (ATF), SNGFR decreased from 63 +/- 2.6 (SE) nl/min at a PR of 16 nl/min to 20 +/- 2.4 nl/min at a PR of 63 +/- 2.6 nl/min. At a PR of 16 nl/min, SFP was 48 +/- 1.3 mmHg with ultrafiltrate and ATF. Increases in PR to 68 nl/min led to a reduction in SFP to 26 +/- 1.5 mmHg. SFP was also measured during changes in PR with various electrolyte solutions of decreasing complexity. Elimination or substitution of Na+, K+, Cl-, HCO3-, and Ca2+ did not significantly alter the magnitude of the feedback response to increases in PR to 68 nl/min. These results confirm the existence of a feedback system in the dog capable of adjusting glomerular function in response to changes in distal perfusion rate. The results based on the various perfusion solutions fail to indicate a unique requirement for any specific component.


Mechanism of the glucocorticoid-induced increase in glomerular filtration rate. In order to investigate the mechanism(s) by which glucocorticoids increase GFR the determinants of glomerular ultrafiltration were measured in two groups of seven Munich-Wistar rats. Group 1 rats were normal controls and group 2 rats were pretreated with methylprednisolone (MP), 15 mg/kg per day for 4 days prior to study. In rats given MP mean values for SNGFR were about 25% higher than in the control group, averaging 33.6 +/- 1.6 (SE) vs. 27.0 +/- 1.0 nl/min. Mean values for initial glomerular plasma flow rate (QA) were also about 25% higher in MP-treated rats, averaging 83.4 +/- 3.9 vs. 65.9 +/- 1.9 nl/min in controls. Mean values of the transglomerular hydraulic pressure difference (deltaP) as well as afferent (IIA) and efferent (IIE) oncotic pressures were essentially similar between control and MP-treated rats. Filtration pressure equilibrium, i.e., equality between IIE and deltaP, obtained in both groups and the mean minimum estimates of the ultrafiltration coefficient (Kf) were also similar between control and MP-treated rats. Thus, the rise in SNGFR following MP is entirely due to the increase in AQ, rather than to changes in the other determinants of ultrafiltration.