Fallopian tube and ovarian hydrocarbons.

Hydrocarbons of the human ovary and Fallopian tube have been studied by temperature-programmed gas chromatography. The major compounds present are a series of n-alkanes (C16 to C40), with the addition of iso and anteiso hydrocarbons. The human ovary and Fallopian tube hydrocarbons did not show significant changes during the menstrual cycle.


Progestational activity of danazol in the human female subject.

A progestational action of Danazol has not been reported in the human subject. Danazol administration for 1 month suppressed serum FSH and estradiol values, and the midcycle LH surge; ovulation promptly resumed after treatment. Administration to patients with polycystic ovarian disease resulted in increased LH values, elevated basal temperature, secretory findings in the endometrial biopsy, and menses. Ovarian biopsy did not document corpus luteum formation, and plasma progesterone did not rise. Administration of Danazol to an ovariectomized patients pretreated with estrogen resulted in an atypical endometrial secretory change. Clinical responses to Danazol may in part be explained by a progestational-like effect of the drug.


The late stage of serpiginous (geographic) choroiditis.

Serpiginous and geographic choroiditis, one and the same disease, is characterized by episodic involvement of the pigment epithelium and choroid. Each new lesion passes through an acute phase into an atrophic and scarring one. We observed 20 patients, some with long-term follow-up; some had eventual widespread involvement of both posterior poles. There was no basis for the disease, and treatment did not affect its course. In the patients with long-term disease there was widespread atrophy of the choroid and pigment epithelium and variable amounts of pigment clumping and subretinal fibrous tissue deposition. In nine patients discrete peripheral patches of atrophy were also found. In some eyes the atrophy at the posterior pole had become so confluent that the condition could have been mistaken superficially for a primary choroidal dystrophy. The uninvolved areas appeared to be normal. The electroretinogram and electrooculogram were only affected when extensive disease was present.


External buckling without drainage for selected detachments in aphakic eyes.

Of 325 patients with retinal detachments, 110 patients (34%) had aphakic eyes. These detachments were subdivided into three types based on their clinical appearance during indirect ophthalmoscopy and slit-lamp biomicroscopy. Fifty-two patients (47%) had aphakic detachments (Type 3), categorized by small tears due to traction along a prominent posterior or vitreous base and the absence of visible retinal degeneration. Fifty of the 52 patients in this group were operated on by using a modification of the nondrainage procedure developed by Custodis, and employing cryosurgical coagulation and an external encircling buckle using a 3-mm silicone sponge. The sponge was secured beneath the retinal tear, and its length was shortened to produce a moderately elevated buckle. Although 50% of retinal tears were open at the end of the operation, 60% of all eyes operated on without drainage reattached in 16 hours, 90% in one week, and the remainder in two weeks. Visual acuity of 70% of these patients was 6/15 (20/50) or better when tested six months after surgery. The operation did not wall away peripheral fluid, but closed retinal tears completely, reduced circumferential vitreous traction, and avoided drainage of subretinal fluid.


Melanocytic lesions of the eyelid skin.

We described the three histogenetic forms of cutaneous melanoma--lentigo maligna melanoma, superficial spreading melanoma, and nodular melanoma. The first two forms have a flat spreading component or radial growth phase in the epithelium as well as in the invasive or vertical growth phase. Formerly these two lesions may have been confused with one another. Nodular melanoma has only the vertical growth phase. Examples of lentigo maligna melanoma and superficial spreading melanoma were found in eyelid lesions involving both the skin and conjunctiva. The distinctive histopathology of the cutaneous lesion was retained in the conjunctiva.


Malignant melanomas of the conjunctiva.

A retrospective study of 23 conjunctival melanomas using the Clark classification revealed that the three most common forms of melanoma described in the skin--lentigo maligna melanoma (Hutchinson's freckle with melanoma), superficial spreading melanoma, and nodular melanoma--can be recognized in the conjunctiva. As in the skin, lentigo maligna melanoma appears to be associated with a good prognosis compared to the prognosis associated with superficial spreading melanoma. These two forms of melanoma are both associated with an intraepithelial stage and had previously been grouped under one designate, cancerous melanosis. They can be distinguished histologically although definite clinical differentiation will be determined in the future. Some melanomas with an intraepithelial stage, however, cannot be definitely classified. Relating all conjunctival cancerous melanoses to Hutchinson's melanotic freckle is no longer justified.


A histologic study of calcific and noncalcific band keratopathies.

One hundred five cases previously diagnosed as band keratopathy were reexamined. We found that band keratopathy was calcific noncalcific, or mixture of both. The noncalcific band was identified as elastotic degeneration of collagen, known clinically by various alternate terms. Cases of so-called reduplication of Bowman's membrane were reexamined, and many demonstrated production of a thick basement membrane of the corneal epithelium, with or without massive calcification. Identification of calcific-band keratopathy was made by transmission electron microscopy even when the tissue had been previously decalcified.


Histologic studies of the vasculature of the anterior optic nerve.

Thirty-one normal human anterior optic nerves were studied in thin serial sections and their vessels stained by standard histologic stains and a new modification of the silver reticulin stain. The retrolaminar cribrosa was profusely supplied by centripetal and longitudinal vessels of pial origin; small branches of the central retinal artery were also seen. Longitudinal continuity of small vessels extended from the retrolaminar nerve to the retinal surface. This system freely anastomosed with three transverse systems; a significant anteriolar input from short posterior ciliary arteries in the sclera to the lamina cribrosa; smaller short posterior ciliary branches and occasional choroidal capillaries to the prelaminar portion; and branches derived from the central retinal artery in and around the disk. Vessels entering the prelaminar region at the level of the choroid were mainly derived from scleral branches of short posterior ciliary vessels entering through the border tissue of Elschnig, rather than from choroidal branches of ciliary arteries. Venous drainage for the anterior optic nerve was primarily through the central retinal vein, although alternate smaller paths to surrounding tissues were also identified.


Electron microscopic study of human papilledema.

Papilledema associated with neoplastic invasion of the orbit in the optic disks of two patients was found and examined by light and electron microscopy. Pathologic changes in the optic nerve head and nerve included axonal degeneration and mild interstitial edema. Axonal swelling appeared to be the major factor in the overall increase in tissue volume of the optic nerve head. Vascular and perivascular glial alterations were nonspecific.


Xerophthalmia and anterior segment blindness.

The prevalence of presumed vitamin A-related corneal scars among 5,589 preschool-age Haitian children ranged from 1.2 per 1,000 in the south, to almost 1% in the famine-afflicted north. These scars accounted for at least 45% of all corneal scars, and all bilateral corneal blindness encountered. Most lesions were acquired during the first three years of life. There was no variation by sex or ecology of the sample site. This country of 5.5 million inhabitants acquires 345 new surviving cases of vitamin A-related corneal destruction, over one fourth bilaterally blind, each year, although local ophthalmologists rarely encounter the disease and Bitot's spots were absent from our study population. Countrywide clinical prevalence surveys are the only unbiased means of determining the magnitude, severity, and geographic distribution of vitamin A-related corneal destruction, prerequisites for the design of public health prevention programs.


Thermokeratoplasty for keratoconus.

Thermokeratoplasty for keratoconus was performed in 29 eyes with follow-up periods ranging from less than four months to 24 months. Twelve patients obtained visual acuity better than 6/12 (20/40). Five patients required corneal transplantation.


Ultrastructure of keratoconus with healed hydrops.

The corneas of three patients with keratoconus were examined by light and electron microscopy within approximately four months after onset of severe hydrops. The rupture and detachment of Descemet's membrane resulted in formation of extensive ledges. New endothelium completely resurfaced the exposed posterior stroma and the corresponding anterior aspect of the ledges. The endothelium also regenerated considerable basement membrane. In one case, clustered endothelium near the free end of the ledge appeared to have undergone fibrous metaplasia with secretion of extensive fibrillar and basement membrane material.


Ocular findings in mannosidosis.

Three patients with typical features of mannosidosis and deficiency of alpha-mannosidase activity, who were examined ophthalmologically, had similar lenticular opacities. Corneal opacities were absent. Chamber angle and striking ophthalmoscopic anomalies occurred in two young patients who had normal electroretinograms. Two patients had strabismus. Conjunctival biopsy specimens morphologically confirmed the lysosomal nature of this disorder.


Clinical and ultrastructural ocular histopathologic studies of adult-onset metachromatic leukodystrophy.

A twin brother and sister with adult-onset metachromatic leukodystrophy developed progressive central acuity loss and optic disk pallor. Both had normal electroretinograms and fluorescein angiography. Postmortem examination of the sister's eyes by histochemistry and electron microscopy revealed ganglion cell loss and optic atrophy. Cerebroside sulfate had accumulated in optic nerve glial cells. Optic atrophy was more advanced than in previously reported cases of infantile-onset metachromatic leukodystrophy. The pathologic process seemed to be retrograde optic nerve degeneration due to abnormal myelin metabolism.


Adrenoleukodystrophy with disease of the eye and optic nerve.

Adrenoleukodystrophy is an X-chromosome-linked recessive disease characterized by primary atrophy of the adrenal glands with or without Addison's disease and low plasma cortisol levels, and a degeneration of white matter of the central nervous system with blindness. In suspected cases of adrenoleukodystrophy an impaired rise in plasma cortisol levels after adrenocorticotrophin stimulation may be diagnostic. With the electron microscope, pathognomonic intracytoplasmic lamellar inclusions have been seen in adrenal cortical cells, peripheral nerve Schwann's cells, testicular interstitial cells, and in macrophages of the brain. Adrenoleukodystrophy appears to be a genetically determined lipid storage disease with an error in membrane sterol metabolism. A 10-year-old boy with adrenoleukodystrophy had visual loss, a prominent early symptom. The ocular abnormality consisted of a disproportionate loss of nerve fibers from the macular region. No intracytoplasmic lamellar inclusions were identified in cells representing macrophages within the optic nerve. They contained myelin debris suggestive of end-stage disease.


Plasma cell infiltration of the conjunctiva associated with pancytopenia, dermatitis, and polyclonal gammopathy.

A 73-year-old man developed conjunctivitis, epiphora, pancytopenia, dermatitis, and a polyclonal gammopathy. Diffuse infiltration and thickening of the conjunctiva and lacrimal canaliculi by plasma cells was present. Histopathologic examination suggested a reactive, chronic inflammatory response rather than neoplasia. The patient's ocular manifestations appeared to be related to his pancytopenia, dermatitis, and polyclonal gammopathy.


Increased intraocular pressure induced by corticosteroids.

Twelve patients who were highly responsive to topically administered betamethasone were subjected to various corticosteroid preparations (four times daily for four weeks). Each patient was tested in the same eye with fluorometholone, tetrahydrotriamcinolone, medrysone, and betamethasone and the potential to elvate intraocular pressure was determined. The response of intraocular pressure to all the corticosteroids was dose-related and a highly significant correlation was demonstrated between the concentration of betamethasone and the magnitude of intraocular pressure response. The order of potential of corticosteroids to elevate IOP was betamethasone 0.1%, betamethasone 0.05%, tetrahydrotriamcinolone 1.25%, betamethasone 0.02%, fluorometholone 0.1%, medrysone 1.0%, and betamethasone 0.01%. Tetrahydrotriamcinolone 0.25% and fluorometholone 0.05 and 0.01% failed to elevate intraocular pressure significantly.


Plasma cortisol suppression test used to predict the development of primary open-angle glaucoma.

Forty patients classified as high responders (GG) to dexamethasone testing (intraocular pressure greater than 31 mm Hg) without visual field loss were subjected to plasma cortisol suppression testing. After a five-year follow-up adequate data were available on 35 patients. Eighteen responded to 1.0 mg of dexamethasone-diphenylhydantoin suppression testing in a similar fashion to patients with primary open-angle glaucoma while 17 responded in a similar fashion to subjects classified as low (NN, intraocular pressure less than 20 mm Hg) and intermediate (NG, intraocular pressure 20 to 31 mm Hg) responders to dexamethasone testing. Eight of the 35 patients developed glaucomatous visual field loss during the follow-up period. These eight patients were not more sensitive to suppression of plasma cortisol than the 27 patients maintaining normal visual fields. Thus, plasma cortisol suppression testing failed to predict the development of primary open-angle glaucoma in GG responders.


Congenital homonymous hemianopia.

We reviewed eight cases of congenital homonymous hemianopia to emphasize the features that may help the clinician to diagnose a congenital disease. The patients were usually unaware of the visual field defect. The hemianopia was usually congruous when incomplete and the opticokinetic nystagmus had a normal pattern. Associated congenital ocular and neurologic abnormalities were common. Clinically recognizable atrophy or hypoplasia of the optic disk was found in all but one of the patients. There was often a history of neonatal or gestational difficulties followed by emotional, behavioral, and learning problems without mental retardation.


An accidental tarsorrhaphy caused by acrylic adhesive.

A 10-year old boy accidently splashed acrylic adhesive in his left eye. I separated the eyelids by cutting adherent eyelashes with the use of a biomicroscope for magnification illumination. Tests with rabbits demonstrated that the solvent nitromethane dissolved the adhesions but diluted the glue and led to adhesions between the tarsal portion of the eyelid and the cornea. I used acrylic adhesions successfully for a temporary relief of irritation in a patient with Bell's palsy.


Marcus gunn (jaw-winking) syndrome.

Association of Marcus Gunn (jaw-winking) syndrome with ipsilateral familial cleft lip occurred in a 17-year-old white boy. He had anisometropia and esotropia with amblyopia of the involved eye. Jaw-winking and blepharoptosis improved to a cosmetically acceptable extent as the child grew older.


Performance in occupational therapy as a predictor of successful prevocational training.

Scores on three subtests of the Minnesota Follow-up Scale (MFS) were related to client outcomes in a prevocational training program in a study of 26 clients who were referred from an adult psychiatric day treatment unit. The results of the study agreed with a prediction that successful performance in occupational therapy in the day treatment unit, as measured by subtest 1, would be significantly related to successful client outcomes. the results regarding predictions for two other subtests were less conclusive because clients received high scores. Age and sex distributions showed that the younger male clients were most likely to be referred for prevocational training. The staff of the prevocational training program accepted the results of the study and also agreed that performance in occupational therapy (in the day treatment unit) should receive greater recognition by staff members as an important indicator of work potential when evaluating clients for referral to a vocational training program. It is planned to continue the use of the MFS in the day treatment unit as an aid for evaluating clients for referral purposes. Scores will continue to be related to client outcomes in the prevocational training program. Further study is also planned concerning the relationship of age and sex and sources to which clients are discharged or referred from the day treatment unit.


Behavior modification: a perspective.

Behavior modification is an approach for changing behavior based on a preliminary study of the individual. Behavior change is attempted once the individual's learning characteristics and the identification of the optimal learning conditions for the learner have been analyzed. The ability to analyze systematically and to develop behavior-environment relationships also brings a responsibility to the user to understand and master the principles and procedures of behavior modification. This article basically ignores the issue of selecting broad treatment goals and the authority of clinicians or teachers to work actively toward achieving these goals. The principal focus is to provide a perspective on the evaluation and use of behavior modification programs based on their conceptual and procedural foundations. Criticisms and the misuse of behavior modification programs are included as well as a set of guidelines for evaluating and developing effective ones.


Relationships between perceptual responses and accident patterns in children: a pilot study.

Many studies have been done to define factors related to accident tendencies in children, but few related these tendencies to developmental lags in visual perception. This pilot study explored the possibility that such a relationship exists. Twelve Caucasian females from similar socioeconomic backgrounds and age ranges were administered the Frostig Developmental Test of Visual Perception. Performance on the perceptual test was compared to accident frequency levels for each child to determine whether or not a correlation between visual perceptual performance and accident frequency existed. Although statistically significant results were not obtained, the need for more definite research related to spatial relations, position in space, and figure ground perception was demonstrated.


Additivity of effects within sectors of the sensitization zone of the Westheimer function.

In this paper, the fourth in a new series, we have examined the properties associated with illuminated sectors of the annular "sensitization" zone of the psychophysical Westheimer function. The results for one-, two-, and four-sector annular background fields indicate simple additivity of effects within the sensitization region when the flashing test field was set substantially above its increment threshold. Under such conditions effects of pattern orientation and borders within the sensitization zone were found to be negligible. The present findings provide a basis for relating the newly developed "transient-like" psychophysical test (which uses a windmill-type stimulus) to the Westheimer function. These data complement earlier clinical analyses of responses by patients whose Westheimer functions were studied near visual field lesions having sharp borders. The latter study is important in localizing this response function in the retina.


Diffraction theory and visual hyperacuity.

The implications of the diffraction theory of light are examined as they relate to visual acuity and hyperacuity. Two incoherent point sources of light give rise to a double-peaked light distribution whose trough is 26% below the adjoining peaks when the sources are separated by Rayleigh limit of resolution, but the dip has vanished when the separation is 80% of the Rayleigh limit. Diffraction theory, however, places no restriction on the precision with which any single source can be localized. No paradox is therefore involved in having a point-spread function with half-width one minute of arc and, at the same time, a localization threshold of a few seconds of arc, although the need for a sophisticated processing mechanism to achieve such low hyperacuity thresholds is emphasized.


Ultrastructural evaluation of the interaction of glucocorticoids and vitamin D on bone cells in thyroparathyroidectomized rats.

To determine the direct effects of cortisol on bone, rats were thyroparathyroidectomized (T(X)PT(X)), fed a low-calcium diet, and given high (50 mg/kg) or low (8 mg/kg) pharmacologic levels of cortisol with or without excess vitamin D3 (15,000 IU). Rats given vitamin D had osteoblasts and osteocytes interpreted ultrastructurally to be actively engaged in matrix synthesis, mineralization of matrix, and in calcium mobilization. Osteoclasts were numerous on metaphyseal trabeculae and in vascular channels of cortical bone. In T(X)PT(X) rats not given vitamin D, osteoblasts and osteocytes were interpreted to have reduced metabolic activity with minimal evidence of participation in bone formation or resorption. Cortisol at both dose levels failed to alter the electron microscopic appearance of osteoblasts, osteocytes, and osteoclasts with or without vitamin D. Bone turnover indicated by urinary hydroxyproline excretion was unaffected by cortisol treatment. These findings suggest that glucocorticoids have little direct action on bone cells and that their effects on calcium metabolism are probably mediated by an interference in intestinal calcium transport and by secondary hyperparathyroidism.


Eosinophil-enriched inflammatory response to schistosomula in the skin of mice immune to Schistosoma mansoni.

Exposure of the mouse skin to Schistosoma mansoni cercariae gives rise to acute, exudative inflammation in both normal and immune mice, but the immune response is anamnestically accelerated and is oesinophil-enriched, thereby enhancing opportunities for tegumental contact of schistosomula with host leukocytes, particularly with eosinophils. Many of the inflammatory changes occurring within the first 48 hours after exposure are due to cercarial products, e.g., "penetration tracts," but some remain demonstrable when schistosomula metamorphosed in vitro are injected intradermally and are therefore directed against the schistosomula themselves, such as the leukocyte "streaming patterns" seen in their pathways. In contrast to earlier observations in primates, cellular responses to schistosomula in the mouse lung 4 days after penetration are minimal in either normal or immune mice. Thus, immune cellular responses to schistosomula in mice are limited to an early time period after cercarial penetration and are morphologically suggestive of an antibody-mediated response rather than of delayed hypersensitivity. Our observations complement earlier evidence suggesting that antibody-mediated host leukocyte contact with schistosomula initiates the killing of challenge parasites in immune mice, with the eosinophil probably playing a crucial role.


A macrophage-dependent factor that stimulates the proliferation of fibroblasts in vitro.

Whole blood serum (HBS) stimulates the proliferation of fibroblasts in vitro, while platelet-poor plasma serum (PPPS) does not. Fibroblasts grown in the presence of PPPS are truly quiescent in that they are not deprived of nutrients in the culture medium and less than 3% of the cells synthesize DNA and divide. In vivo experiments have suggested that macrophages are necessary for stimulation of fibroplasia during wound repair. We have utilized the difference in growth-promoting activity between HBS and PPPS to study the ability of macrophages to produce growth-promoting activity in cell culture. Guinea pig peritoneal macrophages cultured in vitro in medium containing PPPS release into the medium, either directly or indirectly, a factor (or factors) that stimulates the proliferation of guinea pig wound fibroblasts. This macrophage-dependent, fibroblast-stimulating activity (MFSA) is nondialyzable, heat stable (56 C for 30 minutes), and requires culture in vitro for demonstration of activity. The relationship between MFSA and other growth factor(s) has not yet been determined. In contrast to the macrophage, lymphocytes prepared from mesenteric lymph nodes produced no figroblast-stimulating activity.


Effects of lipemia and trauma on experimental fat embolism.

According to some investigators, trauma is thought to bring about physical changes which produce a coalescence of normally dispersed blood lipids into fat droplets and pulmonary fat embolisms. Lipemia is thought to increase the extent of this embolization. If this theory is correct, intravenously infused labeled oil which is retained in the lungs should be mixed with and diluted by the fat emboli originating from the blood. Radioactive olive oil of known specific activity was slowly administered to a) control rats, b) rats made lipemic by dietary measures, c) severely traumatized rats, and d) traumatized lipemic rats. There was no difference in the specific activity of the oil recovered from the lungs of rats of any group, indicating that no recognizable amount of blood lipids had been added to the experimentally produced emboli.


Acute lung injury induced by cadmium aerosol. I. Evolution of alveolar cell damage.

Following exposure to an aerosol of 0.1% (.005 M) cadmium chloride, rat lungs were examined at 6 hours and 1, 2, 3, 4, 7, and 10 days. By light microscopy, damage was multifocal and centered about respiratory bronchioles. Ultrastructurally, there was Type 1 cell edema with frequent loss of surface plasma membranes during the first 24 hours. After 2 days, the number of Type 2 cells had markedly increased, and by 3 days the damaged alveoli were lined by plump cuboidal cells closely resembling Type 2 cells. By 4 days, these cells were flatter, the change being more marked by 7 days; by 10 days, the cells had regained the appearance of Type 1 cells through loss of osmiophilic bodies and superficial microvilli. We conclude that CdCl2 damages Type 1 cells, which are then replaced by proliferation of Type 2 cells. These cells lose their osmiophilic bodies and flatten out to replace the lost Type 1 cells, the process being almost complete by 10 days after the injury. This pattern resembles the injury caused by NO2, O3, and O2.


The adrenal cortex in spontaneously hypertensive rats. A quantitative ultrastructural study.

The adrenal cortex of spontaneously hypertensive rats (SHR) has been examined by quantitative morphologic techniques for electron microscopy. The volume and surface area of smooth endoplasmic reticulum and the volume of Golgi apparatuses in zona glomerulosa cells of SHR was significantly greater than those of Wistar-Kyoto strain (W/KY) normotensive controls; the volume of lipid droplets and nucleus was significantly less in SHR than in W/KY animals. A stimulation of the zona glomerulosa in SHR may well be attributable to the elevation in systolic blood pressure. A distinct lipid-free subglomerulosa was observed in the adrenal gland of W/KY rats; the cell volume was similar to that of the zona glomerulosa although the cells showed a significantly greater volume of mitochondria and surface area of mitochondrial membranes and greater volume of smooth endoplasmic reticulum and lysosomes. In the zona fasciculata, cell volume, volumes and surface area of mitochondria and smooth endoplasmic reticulum, and volume of lipid droplets were significantly lower in SHR than in W/KY rats. The volume of the Golgi apparatus was greater in SHR than in W/KY rats. Glycogen particles were observed in focal areas of some zona fasciculata cells. The adrenal cortex of another strain of normotensive Wistar rat (W/CFN) was compared with that of the W/KY and SHR. Although the relative adrenal weights of SHR and W/KY animals were identical, the weight of that in W/CFN was significantly smaller. The volume of the zona glomerulosa of SHR was significantly greater than that of W/KY although the volume of the zona glomerulosa in W/CFN was significantly greater than the other two groups. The volume of nucleus and lipid droplets of zona glomerulosa in W/KY was significantly greater than that in the S/CFN; the volume of the cell, mitochondria, smooth endoplasmic reticulum, lipid droplets, and lysosomes, and the surface area of smooth endoplasmic reticulum and mitochondrial membranes of W/KY animals was significantly greater than those of W/CFN animals. It is concluded that the W/CFN rat is not an appropriate control for spontaneously hypertensive rats.


Voluntary inhibition of the myotatic reflex and premotor response to joint angle displacement.

EMGs from the deltoid muscle of the nonpreferred arm were obtained from 18 subjects (9 males, 9 females). The EMGs resulted from a stretch reflex (reflex latency) from the fall of the relaxed arm from an electromagnet and from the resultant EMGs of a voluntary response to stop the preceived falling arm (premotor response). Ten normal trials were followed by 10 inhibition trials. By conscious relaxation of the arm and inhibition of the deltoid muscle, all subjects on most trials were able to completely eliminate the voluntary premotor responses. Elimination of the myotatic reflex proved much more difficult with two subjects completely inhibiting it on all trials and ten subjects on at least one trial; however when the reflex was not inhibited, the inhibited condition resulted in significantly reduced reflex duration and an increased reflex latency. No sex difference was found in the ability to inhibit the EMG responses.


Effects of a specific ecutaneous cold stimulus on single motor unit activity of medial gastrocnemium muscle in man.

The effect of a specific skin cooling stimulus on single motor unit (SMU) activity in the underlying medial gastrocnemius muscle on forty normal subjects was examined by computer analysis of the real time occurrence of each unit during a 12 minute experiment. Subjects (N, 17) discharging SMUs at a comfortable resting frequency (5.2 +/- 0.9 Hz) showed a tendency toward inhibitory responses during the first minute of cooling. Most subjects (13 of 18) who discharged SMUs at a frequency of 0.5 Hz underwent a statistically significant increase in SMU activity during the first minute and then a significant reduction in activity during the next minute of cooling. The general findings suggest that motor outflow can be altered in muscle underlying a specific thermal stimulus and that the central excitatory state of the nervous system plays a large role in determining how cutaneous cooling information will be processed to affect motor changes.


Effect of diazepam on muscle contraction in spasticity.

The direct effect of diazepam on skeletal muscle has been examined in 15 patients with neurological lesions resulting in spasticity. Diazepam 15-30 mg. IV reduced the amplitude of the compound action potential of the direct muscle response (M response) and the isometric twitch tension. It is postulated that diazepam may affect the contractile properties of muscle and, possibly, the electrical properties of the muscle membrane. These peripheral effects may contribute to the reported clinical benefits of the drug in patients with spasticity including those patients with complete spinal lesions.


Lengthening contraction and interpretations of active state tension in the isometric twitch response of skeletal muscle.

The plateau of tetanic tension in a lengthening contraction of muscle at any given length is always greater than that in an isometric contraction at the same given length. To account for this excess of tension, it is suggested that the contractile machinery is "locked" in a strained condition that might make the muscle capable of bearing a greater tension in a lengthening contraction than it can develop in an isometric contraction. It is proposed that this strained condition also occurs in a lengthening contraction of the twitch response. If this proposal is valid it seems certain that the plateu of tension in the lengthening contraction of the twitch response cannot be equated with the plateau of tension in the isometric contraction of tetanus. The design of the original concept, that the plateau of active state tension in the lengthening contraction of the twitch is equal to the plateau of tension (Po) in the isometric contraction of tetanus, is based upon the assumption that the contractile component is neither lengthening nor shortening during both of these plateaus. This assumption is made without considering the possibility that the plateau in the lengthening contraction might be due to concurrent lengthening of series elastic elements and shortening of the contractile component. To account for the plateau of tension observed after quick lengthening in the early phase of twitch contraction indirect evidence is presented favoring the view that the quick lengthening during stretch is followed by slow lengthening and stress relaxation (decrease of tension) in series elastic elements and simultaneous shortening and increase of tension in the contractile component. When the original concept of active state tension in the twitch response is interpreted in the light of lengthening contraction, it is concluded that the labeled or implied Po for the plateau of the active state tension is unwarranted and confusing. It seems that the primary source of confusion is the assumption that the tension a muscle is capable of bearing in a lengthening contraction is equatable with the tension it can develop in an isometric contraction.


African fossil tali: further multivariate morphometric studies.

Analysis of measurements from the tali of 21 individual fossil primates from Africa shows that the specimens fall into five clearly defined groups. Accordingly, these specimens have been included as groups along with extant species in a subsequent canonical analysis thus allowing the fossils to play their part in the determination of the canonical separations. The results of this procedure show that the five fossil groups lie in a part of the canonical space not occupied by any extant African primate. Their positions are between the envelope of Asiatic apes (Hylobates and Pongo) and the envelope of African forms near the edge which contains Pan and Papio. One fossil group is so similar to Hylobates that its talus may have functioned in locomotion in a parallel manner. Others lie near to Pongo in directions proceeding towards Pan and Papio and it is possible that this similarity may indicate remnants of morphological adaptation for climbing in these fossils. At the same time, however, individual specimens are closer to one or another of the extant groups and this considerable spread suggests that the locomotor adaptations as evidenced by talar morphology, of the primate fauna in Africa, may have been very different from those of the present day. This would not the inconsistent with the different habitats, floras and non-primate faunas that may have characterized the East African scene at these earlier times. Particular fossils from Olduvai and Kromdraai that are supposed to be australopithecine and therefore bipeds, are confirmed (Oxnard, '72; Lisowski et al., '74) as being totally different from man in their talar morphology and essentially rather similar to the majority of the other fossil tali examined.


Genetic structure and heterozygosity in the kuru region, eastern highlands of New Guinea.

Genetic structure of 20 of the 37 linguistic groups in the Eastern Highlands of New Guinea including the kuru region is analyzed using information on blood groups and serum protein polymorphisms. The average individual is heterozygous at 28.6% of loci and the average number of alleles per locus is 1.234. Coefficients of kinship for linguistic groups range from 0.005 for the sweet potato cultivating North Fore to 0.075 for the isolated Pawaians whose dietary staple is sago and who depend more on hunting and gathering. As one selects linguistic groups with smaller and smaller population size and increasing isolation, one finds that kinship coefficients rise as much as tenfold, but there is no concomitant loss of heterozygosity or trend toward fixation of alleles. Genetic relationships established by genetic distance trees and by principal components analysis are comparable and are consistent with other anthropological observations.


Prenatal origins of carpal fusions.

As shown in 138 embryos and fetuses in the 40-285 mm crown-rump length range, carpal and carpal-metacarpal "fusions" arise from incomplete separation of the cartilaginous precursors rather than from failure of initiation, thus accounting for the "fusions" seen in postnatal radiographs and the grooves that are evident enough in adult fusions. Radiographs selected from over 20,000 apparently normal individuals provide postnatal counterparts for the prenatal examples shown in histological sections.


Paradoxical bilateral asymmetry in bone size and bone mass in the hand.

Among 227 chronic renal disease patients, micrometer caliper radiogrammetric measurements of the second metacarpal at midshaft showed the right metacarpal to be larger (with greater bone area) and with a greater cortical area than the left second metacarpal, both in 208 right-handed individuals and in 19 left-handed individuals. This direction of asymmetry was individually characteristic of the majority of individuals, whether right-handed, left-handed or ambidextrous.


A study of nine polymorphic systems in the population of the Po Delta.

The present work reports a study of nine genetic polymorphic systems in the area of the Po Delta where malaria was endemic since the XIV century. Our data confirm some characteristics of this population already reported by other authors such as the high prevalence of thalassemia, the low prevalence of the rh (d) gene and the presence of G-6-PD deficiency. Among the other systems studied, i.e., AP, PGM1 ADA and AK, only AP frequencies of Po Delta population are significantly different from those of other continental Italian populations, the PC allele showing the lowest frequency so far observed.


Differential contribution of stature phenotypes to assortative mating in parents of Philadelphia black and white school children.

Assortative mating for stature, weight, and the ponderal and Quetelet's indices is considered in a large sample of Philadelphia Blacks and Whites. The husband-wife correlation for stature is positive and significant in Whites (r = 0.34, d.f. = 382), but negligible in Blacks (r = 0.06, d.f. = 420). Correlations for weight and the body indices are positive and significant in both samples, those for body indices showing some dependency on the husband-wife correlations for stature and weight. When couples are grouped into statural mating combinations on the basis of short (S), medium (M) and tall (T), White spouses' statures show an approximately linear relationship to one another. The distribution of Black spouses' statures, however, is not completely independent, even though the husband-wife correlation is close to zero. There are elements of both positive and negative assortative mating among Blacks, resulting in an excess of certain mating types over that expected on the basis of chance. These mating types are usually those in which the husband is shorter than the wife, except at the heterogenous extremes of the bivariate array.


Metering of fluid intake and determinants of ad libitum drinking in rats.

The contributions of homeostatis mechanisms to spontaneous drinking were assessed in a study of residual oral drinking under several conditions of exogenous water administration. Continuous and/or discontinuous infusiors were conducted for long periods with dry food present ad libitum. The routes of administration were intravenous (IV), intragastric (IG) through a nasopharyngeal catheter. All infusions  reduced from noninfused levels, but the magnitude of that reduction was a function of both route and temporal characteristics. Continuous infusions were more effective via the IG route than IV, and a residual intake of about 10 ml/24 h presisted at even the highest infusion rates. Discontinuous meal-paired IV infusions suppressed mid- and postmeal drinking, consistent with the  satisfaction of systemic needs induced by cry food intake. Meal-paired IG nasopharyngeal infusions competely suppressed drinking when the infusions exceeded  base-line intake by only about 20%. In marked contrast, corresponding IG infusions through a direct fistula catheter were relatively ineffective. In all cases the decreases in drinking were not of a nonspecific nature beacuse food intake was unchanged. The discussion considers the different levels of metering involved and the time-varying (derivative) nature of the infusion if was suggested that there is a nonhomeostatic contribution to normal drinking.


Isohemic blood volume expansion in normal and areflexive dogs.

The hemodynamic and renal responses to rapid intravascular volume expansion (VE) were studied in normal and areflexive dogs. "Isohemic" expansion was performed by infusing autologous blood (averaging 453 ml) thoroughly mixed with the circulating blood. In areflexive dogs cardiac output and arterial pressure doubled immediately after VE and fell back to control within 70 min; in normal dogs the circulatory response was less than one-third as great, but arterial pressure failed to return to control within 120 min. In the areflexive dogs, water, electrolyte, and total osmolar urinary output rose three- to fivefold after VE and declined thereafter, roughly following arterial pressure. In normal dogs the urine flow increased 40% immediately and rose further up to 70% in 60 min. No evidence for a natriuretic hormone was seen. It is concluded that mechanical factors are mainly responsible for the increased excretion of water and solutes after VE. Direct nervous reflexes to the kidney seemed to play a quantitatively minor role in the renal response.


Arachidonic acid in splanchnic artery occlusion shock.

Arachindonic acid infused into the mesenteric vascular bed of normal pentobarbital-anesthetized dogs at a concentrations of 150 mug/kg per min produced no significant changes in mean arterial blood pressure (MABP), portal vein pressure (PVP), screen filtration pressure (SFP), platelet count, circulating lysosomal enzyme or myocardial depressant factor (MCF) activities, nad only modestly increased superior mesenteric arter flow (SMAF)ans endogenous prostaglandin concentrations concentrations. It is concluded that arachidonic acid, at the infusion rate employed, dose not have any major effect on the circulatory status or on the lysosomal or platelet stability in normal dogs. In contrast, arachidonic acid administered to dogs in splanchnic artery occulusion (SAO) shock significantly exacerbated the decline in MABP seen after release of the occlusive clamps and also significantly reduced mesenteric blood flow. The hypothnsive of arachidonic acid appears to be partly due to the fatty acid itself and partly due to the metavolically formed prostaglandin endoct the platelet count or aggregability, lysosomal hydrolase activity, or MDF formation in the SAO shock dogs. These data suggest that increased endogenous prostaglandin concentrations in themselves are not a prime factor in the pathophysiology of circulatory shock, but that endogenous prostaglandin or related substances can significantly modulate the shock state.


PCO(2) and rate of formation of cerebrospinal fluid in the monkey.

Changes in cerebrospinal fluid formation rate (VF) with hypocapnia were measured by the ventriculocisternal perfusion technique in 24 rhesus monkeys anesthetized with nitrous oxide. In addition cerebral blood flow (CBF) was measured by the hydrogen clearence methods, Vf in control animals declined at a mean rate of 2.3 mul/min each hour during the last 4.5 h of a 7-h perfusion although variables known to effect Vf remained stable. Three hours after perfusion began, Vf of normocapnic controls was 41.4 mul/min +/- 5.4; CBF, 59P ML/100 G PER MIN. When Pco(2) was reduced to half of control, Vf fell to 35.6 mul/min +/- 6.3 and CBF fell by 27%. When Pco(2) was doubled, Vf fell to 33.1 mul/min +/- 5.3 and CBF increased threefold. The difference in Vf id significant only for the hypercapnic group (p=0.01). When animals were used as their own controls, three were no significant differences in Vf with hypercapnia compared to normocapnia. These results indicated that in the monkey variations of Pco(2) within broad physiologic limits, which are sufficient to cause large changes in CBF, have little effect of Vf.


Pineal multiunit activity in conscious quail: effects of light, blinding, ganglionectomy.

Multiunit activity (MUA) was recorded from thr pineal gland in unanesthetized male Japenese quail. The influence of light regimen on spontaneous and flash-evoked firing patterns of pineal cells was investigated. Shortening the day length from 18 to 6 h/24 h resulted in a marked increase in pineal MUA. Pineal firing rate was higher during the dark than during the light fraction of the photoperiod. Flashlight stimulation always led to a marked inhibition of the pineal MUA. Cutting the optic nerves bilaterally resulted in a marked increase in the level of MUA. None of the experimental conditions altered the elevated MUA in blinded birds. Thus, photoperiod and light stimulation appeared to be important for pineal activity; however, no direct photosended quail. Superior cervical ganglionectomy resulted in slightly increased spontaneous MUA but did not inhibit pineal responses to flashlight stimulations.


Effects of lactate and glutamine on palmitate metabolism in rat kindey cortex.

Rat renal cortical slices were incubated with [1-(14)C]palmitate bound to 2.5% albumin. The following effects were found: a)1 mM palmitate utilization or oxidation to CO(2) varied according to the concentration of lactate in the media, it increased at 0.8 and 3.2 mM, was unchanged at 8 mM, and decreased at 16 mM. Esterification was stimulated at 3.2 mM lactate. b) Addition of glutamine (0.1 mM) instead of lactate stimulated incomplete and complete oxidation of palmitate (1 mM), whereas high medium glutamine (10 mM) inhibited palmitate (1 mM) utilization, esterification, and oxidation to CO(2) but increased its incomplete oxidation. The low rate of exogenous palmitate oxidation observed in this study and the finding that exogenous palmitate oxidation is only partially inhibited at very high concentrations of exogenous lactate or glutamine are consistent with the view that these exogenous substrates contribute little to the oxidative metabolism of rat renal cortex in vitro, which probably depends on the supply of substrates endogenous to the tissue.


Hyperosmolarity: effects on nerves and smooth muscle of cutaneous veins.

Helical strips from dogs' saphenous veins were mounted in an organ bath (Krebs-Ringer solution, 37 degrees C) for isometric tension recording. Additional strips were incubated with [7-3H]norepinephrine and mounted for superfusion and isometric tension recording. The perfusate was collected every 2 min for estimation of total radioactivity and for column chromatographic separation of [3H]norepinephrine and its metabolites. Increasing osmolarity by sucrose caused a slow contraction that was maximal at 500-550 mosM and was accompanied by a reduction in total 3H efflux. The contraction was unaffected by a Ca2+-free medium, alpha-adrenegic blockade, and beta-adrenergic stimulaton. It was depressed by cooling (29 degrees C) and by anoxia combined with a glucose-free medium. Contractions elicited by K+ and Ba2+ were augmented by hyperosmolarity, but those caused by sympathetic nerve stimulation, tyramine, and norepinephrine were depressed. The output of [3H]norepinephrine during nerve stimulation was reduced. Thus, the hyperosmolarity causes 1) contraction of vascular smooth muscle, 2) augmentation of the contractile response to K+ and Ba2+, 3) depression of the excitation caused by norepinephrine, and 4) inhibition of the neuronal release of norepinephrine.


Thermoregulatory effects of monoamine potentiators and inhibitors in the rat.

Exogenously administered monoamines may elicit variable thermoregulatory responses dependent on dosage, species, site of administration, ambient temperature, etc. In an attempt to reconcile several inconsistencies, we have undertaken a series of studies related to monoaminergic control of temperature regulation. Thus, intraventricular administration of serotonin (2.64-26.4 mug) and norepinephrine (3.3-32.8 mug) in rats evoked acute (15-60 min) dose-dependent hypothermic responses (delta Tre = 2 degrees C) that were gradually superseded by significant, more persistent hyperthermia (delta Tre = 1 degreee C). Administration of chlorimipramine or imipramine (total dose 40 mug), even in monoamine-depleted animals, caused long-lasting hyperthermic responses, presumably by the prevention of reuptake of serotonin and norepinephrine at nerve terminals involved in thermoregulation. Pretreatment with the serotonin inhibitor cyproheptadine (4o mug) attenuated the hyperthermia achieved by central administration of chlorimipramine alone. We conclude that both monoamines can act as thermogenic agents under the conditions of these experiments.


Metabolic adaptations in brown adipose tissue of the hamster in extreme ambient temperatures.

Cold acclimation caused the following changes in the brown adipose tissue (BAT) of the hamster: the relative weight of the tissue increased, it color darkened, the multilocular structure predominated, and tissue protein content increased while fat content decreased. There was also an increase in the mitochondrial protein content. Heat acclimation had the opposite effects, i.e., the color became lighter, total and mitochondrial protein decreased, fat content increased, and tissue structure was mostly unilocular. Accordingly, cold acclimation was accompanied by increased tissue respiration in the presence of chi-glycerophosphate (chi-GP) and succinate, whereas heat acclimation reduced the respiratory activity of the tissue with these substrates. Isolated BAT mitochondria from cold-acclimated animals increased activities of chi-GP and NADH oxidase, whereas the activities of succinic and cytochrome oxidases and the amount of mitochondrial cytochromes were unchanged. The effects of heat acclimation were more pronounced: there was a decrease in the activities of chi-GP, succinic, NADH, and cytochrome oxidases, as well as in the cytochrome a and a3 content. When respiration of tissue slices on succinate was compared to the maximal potential respiration, as measured with mitochondria disrupted by freezing and thawing, it was found that the relative activity (slices vs. disrupted mitochondria) was highest in cold-acclimated animals and decreased progressively with increasing acclimation temperatures. It is suggested that the differences in the apparent activity of the mitochondria were due to changes in the conformation of the mitochondria as a result of acclimation.


Influence of vasopressin and amiloride on shunt pathways of frog skin.

Studies were done to determine the influence of vasopressin and amiloride on the sodium backflux of nonedge-damaged frog skin. As before, the bidirectional fluxes of sodium appeared to be limited primarily to the active transport pathways of control skins. When the skins were treated with vasopressin, the sodium backflux was increased selectively (over that of sucrose) and more so than  was expected for the active transportpathway alone. In control skins, amiloride had no effect on the flux of the shunt pathway. However, with vasopressin-treated skins, amiloride at 10(-6) M decreased the sodium backflux of the shunt pathway to levels observed previously for the control skins. These observations are compatible with the idea that the shunt pathway may in part be cellular and in part extracellular. When the changes in open-circuit voltage and shunt resistance caused by vasopressin and amiloride (as determined from the I-V relationships) were examined, the data were also found to be compatible with the idea that vasopressin exerted an influence on the shunt pathway of the frog skin, and this effect of vasopressin could be reversed by amiloride.


Rise in plasma alpha-amino nitrogen concentration in rats eviscerated after colure regulation.

Rats were exposed to 4 or 25 degrees C for 6, 12, and 24 h or for longer periods up to 2 wk, then eviscerated. The hourly changes in plasma alpha-amino nitrogen were followed for 4 h after operation, which because of functional removal of the liver allows amino acids released from the extrahepatic tissues to accumulate in the blood. Although cold exposure of tissues to accumulate in the blood. Although cold exposure of 24-h-fasted rats for 6 h before eviscerated resulted in an increased rate of rise of plasma alpha-amino nitrogen postoperatively, the rise was not significantly greater than warm controls until after 12 h of exposure. Thereafter, similar results were obtained whether cold was 12, 24, or 48 h or 14 days duration. Fasting in the cold produced an immediate sharp rise after evisceration so that the concentration was 2 times the control value in 2 h. By contrast, animals allowed to eat adlibitum showed the rise after evisceration but it was progressively smaller in amount as the exposure extended beyond the 1st day. After 5 days there were no longer significant differences from control values. The reduction in rate of rise in plasma alpha-amino nitrogen coincided with cold-induced increases in food intake. The findings support the view that protein metabolism of muscle, the predominant extrahepatic tissue, may participate in thermogenesis when other sources of energy in the body have been depleted.


Reversal of hypoxic bradycardia by halothane or midcollicular decerebration.

Previous work suggests a primary vagal bradycardia during hypoxic excitation of the arterial chemoreceptors. In this study we examined whether tachycardia, resulting from withdrawal of vagal inhibition of the cardiac pacemaker, may also occur during hypoxia. Cats with cervical spinal section were ventilated with hypoxic gas mixtures or allowed to remain apneic in expiration while heart rate was continually monitored. During recovery from halothane anesthesia or following electrolytic midcollicular decerebration, the bradycardic response to hypoxic or asphyxic stimulation was reduced or was reversed to tachycardia. The extent of reduction or reversal of the bradycardia was positively correlated with the level of the arterial pressure which was adjusted by either hemorrhage or infusion of phenylephrine. These findings indicate a tachycardic component of the vagal response to hypoxia, integrated in the pontomedullary region of the brainstem and resulting from interaction between the chemoreceptor and baroreceptor reflexes.


Influence of medium tonicity on respiration by suspensions of human platelets.

We describe the use of graded decrements of medium osmolarity to progressively unmask respiratory capacities of whole human platelets in suspension. This departure led to the first demonstration that human platelet mitochondria are capable of tightly coupled respiration that responds to addition of mitochondrial substrates, ADP, and inhibitors in a way that other mammalian mitochondria are expected to behave. In 300 mosM media added alpha-glycerophosphate (G3P), succinate, or ADP effected only slight stimulation of base-line O2 consumption. At 180 mosM O2 consumption peaked and was not significantly affected by succinate or ADP. At 80 mosM base-line O2 consumption fell precipitously and was restored by G3P or succinate prior to being raised to its highest levels by ADP. Added NADH had no effect on O2 consumption at 80 mosM but sharply stimulated it when platelet suspensions were exposed to 60 mosM media by pretreatment with distilled water. At 80 mosM, selected compounds that inhibit or uncouple oxidative phosphorylation of isolated mammalian mitochondria from a variety of cells exerted similar influences on while platelets.


Fever and antipyresis in the lizard Dipsosaurus dorsalis.

Lizards (Dipsosaurus dorsalis) were placed in a desertlike environment in which the ambient temperature (Ta) at night (1800-0600 h) was 12 degrees C and the day (0600-1800 h) Ta was between 30 and 55 degrees C depending on the location within the chamber. When dead Aeromonas hydrophila (4 X 10(9) organisms) was injected into nine lizards, an elevation in body temperature (Tb) of 2.7 degrees C was observed during the same day. On the day after bacterial injection the lizards' body temperatures averaged 41.6 degrees C, an increase of 4.2 degrees C over their control day Tb. Further investigations on the febrile response of D. dorsalis were conducted at the University of Wisconsin's Biotron, where there exists a simulated desert environment with the light intensity, temperature, and humidity closely parelleling a typical spring day in the southwestern desert of the United States (the natural habitat of Dipsosaurus). In this environment injection of dead bacteria into seven lizards led to an average febrile response of similar magnitude (Tb = 40.5 degrees C) but with a longer latency than that found at the University of Michigan. Injection of 13 lizards with live A. hydrophila (5 X 10(9) organism subcut.) in the simulated desert at Michigan led to a daytime fever averaging 2.3 degrees C (mean Tb = 40.6 degrees C) over a 5-day period. During the 6th and 7th day the lizards' body temperature returned to the normal or afebrile level. Injections of sodium salicylate along with dead A. hydrophila resulted in a dose-dependent attenuation of the febrile response. These results demonstrate that the reptilian febrile response is strikingly similar to avian and mammalian fever and suggest a common origin and perhaps function for the febrile mechanism.


Responses of rat brainstem neurons to carotid occlusion.

The distribution and features of cardiovascular neurons (CVN) were studied in the brainstem of chloralose-anesthetized rats. Only neurons yielding an immediate response to carotid occulsion (CO) were considered as CVN. The criterion was deduced from the response patterns of cardiovascular afferent (carotid sinus nerve) and efferents (sympathetic and vagal nerves) during CO. Seventy-two CVN were identified and were observed to be mostly in the medullarly reticular formation and to some extent in the nucleus tractus solitarius and nucleus ambiguus. Fifty-five CVN (type A) decreased their firing rates in response to CO where 17 CVN (type B) increased their rates. Analyses of the time courses of their responses to CO revealed the convergence of the chemoreceptor and baroreceptor inputs onto some type A neurons. Electrical stimulation of the spinal cord evoked orthodromic responses in some neurons in both types. The evoked responses were blocked by CO in type A neurons whereas they were facilitated in those of type B. These results suggest that input from arterial baroreceptors, arterial chemoreceptors, and spinal ascending afferents is integrated within CVN.


Effects of 4-pentenoic acid on renal phosphate and calcium excretion in the dog.

The effects of 4-pentenoic acid (4-PA) on renal excretion of phosphate and calcium were studied in anesthetized mongrel dogs. The major metabolic action of 4-PA is inhibition of long-chain fatty acid oxidation. In intact dogs undergoing modest saline diuresis, 4-PA caused significant decrease in the percentage of filtered phosphate reabsorbed. No statistically significant calciuria was observed. Similar results were observed in intact dogs undergoing more brisk saline diuresis as well as in acutely and chronically thyroparathyroidectomized dogs. However, when results were pooled, both phosphate and calcium excretions were significantly increased. The results are interpreted as demonstrating the importance of fatty acid oxidation in providing energy for the work of tubular phosphate reabsorption. Either the energy source for calcium reabsorption differs from fatty acid oxodation, or calcium reabsorption is less sensitive to changes in energy sources. The action of 4-PA is independent of the forces involved in saline diuresis and of parathyroid hormone.


Further studies on coupling between sodium transport and respiration in toad urinary bladder.

When sodium transport (JNa) and CO2 production (JCO2) were measured simultaneously in the toad urinary bladder in the absence of electrochemical gradients under conditions of spontaneous variation of JNa, the curve of JNa on JCO2, phiJNa/phiJCO2, was found to be highly linear in an individual epithelium. However, no unique value appeared to characterize a population of bladders. In an effort to investigate the nature of this variation, phiJNa/phiJCO2 was examined under a variety of conditions. It was found that agents that affect sodium entry into the active transport pool, e.g. vasopressin and amiloride, or those that influence the energy-linked exit step, e.g. ouabain and insulin, have no effect on the phiJNa/phiJCO2. To investigate the possibility of the presence of a significant backleak from the serosal side into the cell, the sodium concentration was changed to 75 and 160 mM. Neither of these maneuvers influenced phiJNa/phiJCO2 or (JCO2)JNa=O. Furthermore, in the absence of mucosal sodium, ouabain had no effect on JCO2, suggesting that no significant recirculation is occurring. It is concluded that for each individual epithelium JNa is coupled to JCO2, and their ratios appear, within experimental error, to be invariant. It is suggested that sodium traverses the active transport pathway largely or entirely in one direction.


Propagation of stimulated slow waves in cat intestinal muscle.

This study was designed to examine the propagation and propagation failure of the slow wave. Spontaneous slow waves and action potentials were recorded from the longitudinal muscle layer of small strips of cat jejunum. Slow waves could be stimulated electrically at intervals shorter than the spontaneous interval, and the velocity of propagation of these slow waves was slower than the spontaneous slow waves. The velocity of propagation was approximately proportional to the time between slow waves. At intervals about one-half the normal spontaneous interval the propagation became slow and unstable, which would result in the periodic failure of a single slow wave. This type of failure may underlie the formation of the slow-wave frequency gradient observed in the intact intestine. The wave shape of the external recording of the slow wave, together with the measurement of electrotonic current spread in strips of isolated muscle, suggest that the slow wave propagates by local circuit currents in an electrically excitable cablelike tissue.


Determinants of glomerular filtration rate in the dog.

Micropuncture techniques were used to evaluate the determinants of glomerular filtration in hydropenic dogs. Stop-flow and servo-null techniques were used to estimate the glomerular capillary and proximal tubule hydrostatic pressures. The validity of stop-flow estimates was verified by comparisons with direct puncture of glomerular capillaries in Munich-Wistar rats. Efferent arteriolar oncotic pressure was calculated from the filtration fraction and systemic protein concentrations. This calculation was verified in separate experiments by measurement of the protein concentration in blood collected directly from efferent arterioles. In 14 dogs, estimated glomerular capillary pressure (GCP) averaged 65.8 +/- 2.9 mmHg and proximal tubule pressure (PT) averaged 20.5 +/- 1.3 mmHg. The net hydrostatic filtration pressure (GCP - PT) of 45.3 +/- 2.7 mmHg was significantly higher than the efferent arteriolar oncotic pressure (piEA) of 33.2 +/- 2.8 mmHg (P less than .001). These findings indicate that filtration dynamics in the dog are characterized by filtration pressure disequilibrium.


Maturation of contractile response of ductus arteriosus to oxygen and drugs.

Contractile responses of rings of ductus arteriosus from fetal and neonatal guinea pigs were studied in buffered Krebs-Henseleit solutions of various oxygen tensions. Oxygen-induced contraction of ductus arteriosus increased with gestational age, peaking at term and attenuating within 24 h after birth. Contractions of ductus in response to potassium were not different in term and preterm fetuses. Maximal contractile response of pre- and postductal aortic rings to oxygen was 8.3% of the maximal oxygen-induced contraction of ductal rings from the same fetuses. Pulmonary artery was quite insensitive to oxygen. Of 12 ductus exposed to bradykinin in the absence of oxygen seven contracted (maximal response was obtained with 15.0 ng/ml). Exposure of ductus to bradykinin in the absence of oxygen enhanced subsequent contractions of ductal smooth muscle rings to air. Atropine failed to inhibit the oxygen-induced contraction of ductus. These data suggest that acetylcholine is not essential for oxygen-induced contraction of the guinea pig ductus arteriosus.


Intestinal ion transport: effect of norepinephrine, pilocarpine, and atropine.

The effects of parenteral pilocarpine, atropine, and norepinephrine on salt and water transport were studied in jejunum and ileum of anesthetized rats. Pilocarpine increased jejunal transmural PD, reduced absorption of Na, K, HCO3, and H2O, and increased secretion of Cl; in ileum, it caused secretion of Na and H2O, elicited secretion of K, and reduced the absorption of Cl. In both segments, perfusate became more akaline, and there was less of a rise in PCO2. Atropine prevented all changes caused by pilocarpine. Atropine alone increased jejunal absorption of Na and HCO3 and acidity of perfusate, implying that cholinergic nerves influence transport. Norepinephrine augmented jejunal absorption of Na, Cl, and H2O but caused no change in PD. In ileum, norepinephrine increased absorption of Na and Cl, reduced the rise in pH, increased the rise in PCO2 of perfusate, but did not affect net HCO3 movement. With all agents, when Na absorption increased, perfusate became more acidic in jejunum and less alkaline in ileum, evidence of an association between Na and H transport.


Effect of vasopressin on sodium excretion and plasma antinatriferic activity in the dog.

Vasopressin (VP) was administered for 1 h intravenously to hydropenic, anesthetized dogs in doses of 1.0-1.25 mU/kg per min. In 14 experiments, sodium excretion (UNA V) increased from a mean of 13 +/- 5 to a peak of 96 +/- 21 mueq/min 40 min after beginning infusion (P less than .001). Urine flow and potassium excretion increased from 0.18 +/-.04 ml/min and 20 +/- 2 meuq/min to peak values of 0.6 +/- .08 ml/min and 61 +/- 9 mueq/min, respectively (P less than .001), with no significant increase in glomerular filtration rate. No significant changes in UNA V occurred in eight sham control experiments of in six experiments in which VP was given at 75 muU/kf per min. To test the hypothesis that VP might be natriuretic indirectly by releasing a natriuretic substance, plasms ultrafiltrates were tested for toad bladder antinatriferic activity(AA). During steady-state control, AA was -10 +/- 3%. Thirty and sixty minutes after beginning VP, AA increased to -24 +/- 3% (P less than .05) and -26 +/- 2% (P less than .001), respectiviely. No significant change in plasma AA occurred in either sham controls or in animals given the subnatriuretic VP dose. Incubation of plasma with 1,000 muU/ml VP caused no increase in AA. The data show that VP natriuresis is accompanied by an increase in plasms AA. The results suggest that vasopressin natriuresis in hydropenic dogs at least in part to the release of a humoral inhibitor of renal tubular sodium transport.


Effect of serotonin on brown adipose tissue and on its sympathetic neurons.

Previously we have shown that there are two types of sympathetic neurons in the rat interscapular brown fat-pad: long adrenergic neurons with cell bodies located in the paraspinal ganglia and short adrenergic neurons with cell bodies located within the pad itself. The present studies examine 1) the uptake of [3H]norepinephrine by these neurons, 2) the effect of serotonin on release of the catecholamine, and 3) the metabolic action of serotonin on brown fat. [3H]norepinephrine uptake from the medium in which brown fat slices are incubated is linear with time up to 90 min. This uptake is blocked by both cocaine and imipramine. As these drugs block uptake by sympathetic neurons, the [3H]norepinephrine is probably taken up by neurons and not by some other cell in the pad. Serotonin creatinine sulfate, but not creatinine sulfate, promotes the release of the catecholamine from these neurons. Serotonin also exerts a norepinephrine-like metabolic effect on slices of normal brown fat. It stimulates lipolysis and inhibits lipogenesis. Serotonin has no effect on isolated brown fat cells or on slices of reserpinized tissue. It also does not potentiate the action of norepinephrine on these last two preparations. Therefore serotonin's action on brown fat is mediated by norepinephrine-containing stromal cells. The data suggest that the rat brown fat-pad has sympathetic neurons that can take up norepinephrine and that serotonin exerts its metabolic effect by stimulating the release of norepinephrine from these neurons.


Effect of insulin on canalicular bile formation.

Mongrel dogs were prepared by cholecystectomy, ligation of the lesser pancreatic duct, and insertion of gastric and duodenal cannulas. The common bile duct was cannulated through the duodenal fistula. After bile flow had been stabilized by intravenous infusion of sodium taurocholate the dogs were given an intravenous injection of insulin or 0.9% NaCl (control). Insulin caused marked increases in bile flow, chloride output, and biliary clearance of erythritol and small increases in bicarbonate output and bile salt output. The increased erythritol clearance indicates that canalicular secretion contributes to insulin choleresis in dogs.


Effect of potassium on ammoniagenesis by renal mitochondria.

Ammonia production by rat renal cortical mitochondria was studied with both in vivo and in vitro manipulation of potassium to further elucidate the mechanisms relating potassium homeostasis and renal ammonia production. Mitochondria from potassium-depleted animals demonstrated an increase in ammonia production at all glutamine concentrations studied, which ranged from 0.5 to 10 mM. This increase in ammoniagenesis compared favorably in degree of change with and was of sufficient absolute magnitude to entirely account for the findings observed both in renal cortical slices studied in vitro and in the intact animal. When rotenone is added to the medium, increased ammoniagenesis is still detected, indicating that either glutamine entry into the mitochondria and/or the activity of phosphate-dependent glutaminase are critical rate-controlling steps. In contrast to studies with renal slices, a decrease in ammonia production was not apparent with cortical mitochondria from chronically potassium-loaded animals. In vitro alterations of the potassium homeostasis. Therefore, these experimental manipulations either do not activate an effector mechanism which takes place in vivo, or the alteration in ammoniagenesis requires an adaptation over time that is not achieved with this in vitro approach.


Mineralocorticoid activity of 18-OH-DOC and DOCA in dogs with an aortic-caval fistula.

The mineralocorticoid activity of 18-hydroxydeoxycorticosterone (18-OH-DOC) was measured during chronic electrolyte balance studies or during the postprandial increase in electrolyte excretion in conscious dogs with an aortic-caval fistula. In the chronic balance study, daily doses of DOCA and 18-OH-DOC ranging from 1 to 25 mg were administered intramuscularly for 3 consecutive days each, 6 h prior to feeding. For the postprandial study, 2-10 mg of DOCA and 18-OH-DOC were administered at feeding and postprandial electrolyte excretion was measured hourly for 6 h. Sodium and fluid retention in the dogs with an aortic-caval fistula was related to the dose of mineralocorticoid administered and equivalent sodium-retaining responses were achieved with 6-10 times more 18-OH-DOC than DOCA. Rapid absorption of both steroids was suggested from the postprandial measurements of urinary sodium excretion. Slight potassium retention occurred during the chronic administration of large doses of DOCA but the postprandial potassium responses produced by the steroids were variable and suggested a slight kaliuresis. The data also emphasize the importance of mineralocorticoids in sodium retention and ascites formation in this experimental model of high-output heart failure.


Effects of digitalis and calcium on papillary muscles in normal and hypoxic states.

The effects of digoxin and ouabain in 2.5 and 4.0 mM extracellular calcium were studied in well-oxygenated and hypoxic isolated, isometrically contracting cat papillary muscles. Muscle digoxin content was measured at the conclusion of the digoxin experiments. In the well-oxygenated environment muscles in the higher Ca bathing media reached peak glycoside inotropic effect sooner and contained 2.7 times more digoxin. During hypoxia and reoxygenation muscles contracting with glycosides performed no differently than those without a glycoside present. Muscle digoxin content was lowered at the end of hypoxia (P less than 0.05) in 2.5 mM Ca; after reoxygenation digoxin content was significantly greater than either before or after hypoxia (P less than 0.001). Hypoxic depression of muscle performance was attenuated in 4.0 mM Ca but muscles in 2.5 mM Ca showed greater improvement during reoxygenation even though the muscles in 4.0 mM Ca had significantly greater digoxin content at the end of reoxygenation (P less than 0.02). It therefore is concluded that, although altered extracellular calcium can alter performance during hypoxia and reoxygenation, muscle performance is not aided by the presence of digitalis and under these conditions performance cannot be correlated with muscle digoxin levels.


Suppressive effect of endotoxin on erythropietin-responsive cells in mice.

Infection may be associated with failure of erythropoiesis, and endotoxin has been shown to cause a decrease in the number of erythroid cells in the marrow of mice. We have investigated the effect of endotoxin on erythropoiesis in BDF1 mice by studying its effect on the incorporation of intravenously administered 59Fe into peripheral red cells. In normal mice the injection of endotoxin 2 and 3 days prior to the administration of 59Fe results in suppression of its incorporation into red cells. In exhypoxic polycythemic mice, endotoxin suppresses the response to erythropoietin injection when the endotoxin is given prior to or at the same time as the erythropoietin. This effect is much less marked when endotoxin is given after erythropoietin. We conclude that endotoxin either 1) impairs the function of erythropoietin-responsive cells, 2) competively decreases erythroid progenitors by stimulating granulocytes, or 3) inactivates erythropoietin.


Digestion of tripeptides and disaccharides: relationship with brush border hydrolases.

Intestinal digestion of two tripeptides (leucyl-glycyl-glycine, prolyl-glycyl-glycine) and two disacchrarides (sucrose, maltose) was examined in the hamster by intestinal perfusion in vivo and hydrolysis of the substrates by microvillus membranes. Perfusion studies showed that luminal disappearance rates of leucyl-glycl-glycine were significantly higher than prolyl-glycyl-glycine (P less than o.001), sucrose (P less than 0.001), and maltose (P less than 0.005). Hydrolytic products of leucyl-glycyl-glycine, sucrose, and maltose were detected in the gut lumen in appreciable concentrations, whereas negligible concentrations of prolyl-glycyl-glycine products were present. Leucyl-glycyl-glycine hydrolysis in microvillus membranes was markedly higher than prolyl-glycyl-glycine (P less than 0.001), which was predominant in the cytoplasmic fraction. These results indicate that leucyl-glycyl-glycine, like sucrose and maltose, is hydrolyzed at the membrane. With some tripeptides, i.e., leucyl-glycyl-glycine, digestion occurs at the microvillus membrane with subsequent transport of hydrolytic products into the intestinal epithelial cell. Other tripeptides, i.e., prolyl-glycyl-glycine, may cross the membrane and undergo intracellular hydrolysis by cytoplasmic peptidases.


Renal handling of [(14)C]mannose.

The uptake of D-[(14)C]mannose by adult rat kidney cortex slices has been examined. The process involved appeared to be saturable and oxygen dependent and to be inhibited by glucose, galactose, chi-methyl-D-glucoside, and phlorizin. Extensive metabolism of the sugar occurred. (14)CO(2) was produced to an extent comparable to that from D-glucose. Radioactive compounds accumulated in the tissue, approximately 50% of which were in the form of phosphorylated or other polar intermediates. The remaining neutral fraction consisted of mannose with a small amount of label in glucose and an unidentified compound which behaves like an alditol. Mannose concentration in the intracellular fluid was never greater than that of the medium.


Oral contraceptives, norethindrone and mestranol: effects on tissue levels of minerals.

The study involved three levels of dietary zinc (deficient, marginal, and adequate) and four hormonal conditions; namely, no steriods, norethindrone, mestranol, and norethindrone plus mestranol. The steroids were incorporated into diets and fed to 11-wk-old female Sprague-Dawley rats. After 10 wk of treatment, various tissues were excised for mineral assays by atomic-absorption spectrophotometry. Both steroids, reduced weight gain. Mestranol depressed plasma zinc, tibia copper and magnesium, and liver iron, but elevated the zinc levels in liver and erythrocytes, plasma copper, liver magnesium and calcium, and iron content of tibia and heart. In general, the effect was most prominent with adequate zinc but diminished in magnitude with the reduction of zinc intake. In addition, norethindrone increased heart iron and tibia calcium. Mestranol appeared to be the main causative factor and may have induced a possible shift of minerals from one pool to another. As expected, zinc deficiency resulted in the reduction of zinc concentrations of plasma, tibia, kidney, and pancreas, and the elevation of copper, iron, magnesium, and calcium concentrations of various tissues.


Permeability of renal peritubular capillaries to neutral dextrans dextrans and endogenous albumin.

Renal lymph-to-renal vein concentration ratios (CL/CV) for neutral dextrans (18-42 A effective radii) and endogenous serum albumin were measured in rats before and during acute colume expansion with isoncotic plasma or Ringer solution. Under all conditions studied, CL/CV decreased with increasing dextran size, in normal hydropenia falling from 0.93 +/- 0.03 SE at 18 A to 0.24 +/- 0.02 a 42 A (n = 12). Albumin (36 A pradius) behaved in a manner similar to a 40 A dextran, CL/CV averaging 0.33 +/- 0.03 (n = 12) in hydropenia. For all dextran sizes studied and for albumin, CL/CV decreased markedly during either form of volume expansion. Ringer loading produced significantly greater decreases in CL/CV for the larger dextrans and albumin than did plasma loading, and also resulted in much greater increases in renal lymph flow, while causing increases in whole kidney fluid reabsorption similar to those with plasma loading. With a compartmental model in which diffusion of dextrans and albumin from capillary lumen to interstitium is opposed by capillary uptake of tubule reabsorbate, these results are interpreted to indicate that connective reflection coefficients for dextrans with radii great than or equal to 36 A and albumin are essentially equal to 1. Indirect evidence is therefore provided that albumin and the larger globulins exert their full osmotic pressures across the walls of peritubular capillaries.


Hepatic venous compliance and role of liver as a blood reservoir.

Changes in hepatic blood volume in response to rapid elevations in hepatic venous pressure were examined in cats using hepatic plethysmography. The liver was intact and received blood from an intact portal vein and hepatic artery. The hepatic blood volume increased in response to elevated venous pressure. Compliance of the hepatic capacitance vessels became greater as the distending venous pressure was increased over the range of venous pressures studied (0-9.4 mmHg). When hepatic venous pressure was elevated to 9.4 MMHg, the hepatic blood volume more than doubled. The liver serves as an important buffer for rapid changes in blood volume, the importance increasing with greater infused volumes of fluid. While overall venous compliance decreased at distending pressures in excess of 5-6 mmHg, the compliance of the hepatic capacitance vessels shows marked increases at pressures above this level. Expansions of the blood volume results in elevations of central venous pressure. Within a few minutes the hepatic capacitance vessels sequester a significant proportion of the added volume. As long as central venous pressure is raised, the liver demonstrates a secondary fluid buffering role by filtering large volumes of fluid across the vascular bed into the peritoneum.


Sympathetic nervous control of cat ileocecal sphincter.

A perfusion method was designed in order to investigate that effects of stimulation of the splanchnic and lumbar colonic nerves on the ileocecal sphincter (ICS) of the cat. Splanchnic and lumbar colonic nerve stimulation at physiological frequencies, i.e., below 10-12 impulses/s, elicited a contraction of the sphincter concomitant with an inhibition of the motility of the adjacent parts of the small and large intestines. It is concluded that the splanchinc and lumbar colonic nerves contract the ICS by a direct effect on the sphincter and not via a contraction of the intestine surrounding the sphincter. Guanethidine and phenoxybenzamine but not propranolol blocked the contraction of the ICS. It is suggested that the splanchnic and lumbar colonic nerves control the sphincter via an alpha-adrenergic mechanism. Inhibitory fibers within the splanchnic or lumbar colonic nerves to the ICS were not found. The excitatory in the ICS elicited by adrenaline, nor-adrenaline, or phyenylephrine infusion was completely blocked by phenoxybenzamine. Propranolol did not block the effect on ICS of these drugs. On the contrary, an augmented response could be shown, indicating unmasking of an excitatory alpha-receptor response by blockade of inhibitory beta-receptors. Further support for these inhibitory beta-receptors was provided by the finding that isoprenaline had a relaxing effect on the sphincteric muscle, an effect that was blocked by propranolol. In order to block the inhibitory effect on the small and large intestine elicited by splanchnic and lumbar colonic nerve stimulation, both phenoxybenzamine and propranolol had to be administered.


An examination of transcapillary water flux in renal inner medulla.

We recently demonstrated that net fluid uptake occurs in the capillary system of the inner medulla. To define the site of fluid uptake, the concentration of protein was determined in plasma from descending vasa recta at the base and tip of the exposed papilla in Munich-Wister rats. The vasa recta plasma-to-arterial plasma protein concentration ratio (VR/P) was 1.43 +/- 0.09 at the base and 1.66 +/- 0.09 at the tip. These results, which indicate fluid loss from the descending vasa recta, are difficult to explain on the basic of hydraulic and oncotic forces alone. The osmolality of the contents of descending vasa recta increased between base and tip (delta = 72 +/- 30 mosmol/kg H2O). If the increase in osmolality of plasma in descending vasa recta lags behind that of the adjacent medullary interstitium, a transcapillary osmotic driving force exists favoring water loss from descending vessels. It is concluded that fluid uptake by the inner medullary circulation occurs beyond descending vasa recta in interconnecting capillaries or ascending vasa recta. In our view the most likely interpretation of these results is that fluid movement across vasa recta in the inner medulla is influenced by three forces: those owing to transcapillary differences in osmotic, oncotic, and hydraulic pressures.


Role of sinoatrial ring bundle in internodal conduction.

The role of the sinoatrial ring bundle (SARB) in internodal conduction was examined by the microelectrode technique in excised rabbit hearts. The spread of the sinus impluse to the surrounding tissues was shown to proceed anteriorly toward the right branch of the crista terminalis significantly faster than toward the other direction. Thus the right SARB and the right branch of the crista terminalis close to the sinus node were the earliest areas excited by the sinus impulse in the areas surrounding the sinus node. It was further shown that the activation sequence does not initiate from the right SARB to the right branch of the crista terminalis via the junction of these two structures. Cutting the SARB did not produce any delay in conduction from the sinus node to the atrioventricular (AV) node. The conduction velocity measured at the endocardial surface by two microelectrodes has proved that conduction in the crista terminalis was significantly faster than in the SARB. The upstroke of the action potential from the crista terminalis was also steeper than that from the SARB. These results suggest that the SARB is not the main route for impulse propagation from the sinus node to the AV node; the fastest internodal conduction therefore takes place with wide wave fronts, along the crista terminalis.


Renal excretion of urate in mongrel and Dalmatian dogs: a micropuncture study.

Free-low micropunction experiments were performed in mongrel dogs and in Dalmatian coach hounds infused with urate to obtain Purate levels of 0.15-0.21 mM before and during the infusion of pyrazinioc acid (PZA). In the absence of PZA, mongrel dogs excreted approximately 50% and Dalmatians 140% of filtered loads of urate. In mongrel dogs net reabsorption occurred only in the proximal convoluted tubules. PZA enhanced net proximal reabsorption and revealed the occurrence of proximal secretion, whereas fractional urate excretion in the urine decreased only slightly. In Dalmation dogs urate fluxes across walls of proximal convoluted tubules resulted in either net reabsorption or net secretion, with no mean change. Net urate secretion occurred between superficial late-proximal and early-distal tubules, and considerably decreased fractional excretion of urate. The renal handling of PZA was similar in mongrel and in Dalmatian dogs.


Left ventricular force-length relations of isovolumic and ejecting contractions.

To determine the interrelationships between ejecting and isovolumic force-length relations and the extent to which the left ventricle will shorten, data obtained in 27 isolated, servo-regulated hearts were examined. For each heart a series of contractions, variably loaded (delta L) were derived for a thickwalled sphere and normalized by the cross-sectional area of muscle and length at zero end-diastolic pressure. It was found that within the physiological range examined total and active force were essentially a linear function of initial L with respective increments or reductions in slope produced by positive or negative shifts in contractile state. The force-L relations obtained isovolumically and at end ejection were virtually identical. For a given ejection pressure, end-systolic L was constant, despite variations in filling and therefore independent of initial L and deltaL; moreover, the L to which the ventricle shortened was determined by the course of the systolic force L-relation. Thus, irrespective of loading, delta L occurs within the confines of the contractile state-dependent isovolumic force-L relation and where the latter is equivalent to the end-systolic force-length relation.


Fibrin-induced release of platelet serotonin.

Human platelets were reacted with polymerized fibrin formed from human fibrinogen. The platelets adhered to the fibrin particles and this adhesion was followed by the release of serotonin from prelabeled platelets. The adhesion of platelets to fibrin was not inhibited by adenosine or prostaglandin E1. However, the subsequent Ca2+-dependent release of platelet serotonin was completely inhibited by these compounds. After the initial platelet-fibrin interaction, ADP and serotonin released from activated platelets may lead to additional platelet aggregation and release. Therefore, in addition to clot stabilization, fibrin serves as an initiator of the platelet release reaction. This in turn initiates the self-amplifying process of platelet aggregation.


Lactate production in isolated perfused rat lung.

The ability of the isolated perfused rat lung to produce lactate under aerobic and hypoxic conditions has been studied. The lung has been found capable of producing lactate at a rate of 53 mumol/g dry wt per h in the presence of as great as 1 mM extracellular lactate under aerobic conditions. Essentially 100% of the lactate synthesized was derived from [U-14C]glucose. When hypoxic, the rate of lactate production doubled, but only 60% was found to be derived from [U-14C]glucose. When the perfused lung was exposed to aerobic conditions following hypoxia, it was found that lactate production did not decrease. However, lactate production from [U-14C]glucose did increase. It is concluded that lung tissue possesses a high rate of lactate production under aerobic contitions from glucose in comparison to glucose oxidation to CO2. When the lung is hypoxic, lactate production increases as a probable result of amino acid catabolism with little anaerobic energy production occurring. The effect of hypoxia was not reversed within the duration of the performed experiments.


Glucagon, insulin, and gluconeogenesis in fasted odd carbon fatty acid-enriched rats.

Forty-eight male rats were fed a nutritionally complete diet containing 30% of dietary energy as fat. For 24 animals (control) the fat source was corn oil, for the remaining 24 rats (experimental) the fat source was a triundecanoin-corn oil mixture (7:3, wt/wt). After 6 wk, groups of control and experimental rats were killed after 0, 24, and 48 h of fasting. In the experimental group, adipose tissue fatty acids contained, on average, 280 mmol undecanoate/mol fatty acid. In the control group, no odd-numbered fatty acids were present. During fasting, the experimental groups had higher plasma glucose and alanine levels, higher plasma insulin-to-glucagon ration, and lower liver phosphenol pyruvate caboxykinase. The results suggest that the terminal propionate residues generated when odd carbon fatty acids are oxidized become gluconeogenic precursors and cause a reduced need for gluconeogenesis from protein.


Renal urate excretion at various plasma concentrations in the rat: a free-flow micropuncture study.

Free-flow micropuncture experiments were performed in male Sprague-Dawley rats undergoing moderate mannitol diuresis and infused with urate-containing solutions. The resulting plasma urate concentrations ranged from 37.5 +/- 2.4 to 601.2 +/- 23.8 muM. With urate loading, the fraction of filtered urate excreted in pelvic urine increased from 0.32 +/- 0.02 to 0.92 +/- 0.05 mu M, but net secretion was not observed. At normal urate levels net reabsorption occurred along superficial proximal tubules, whereas net secretion could be demonstrated at the highest plasma urate levels. Net movements of urate did not appear to occur across the walls of the lower segments of nephrons.


Time course of ureteral changes with obstruction.

Chronic obstruction is characterized by a marked degree of ureteral dilatation and tortuosity which develops in the presence of a relatively low intraluminal pressure. To define the mechanism for the development of this relationship,  the pressure-tension-deformation relationships of acute and chronically obstructed ureters were investigated. Rabbit ureters, in vivo, were obstructed and deformation correlated with intraluminal pressure. During the initial 3 h of obstruction, ureteral resting pressure increased from approximately 0 to 42 cm H2O, and diameter increased 16% with a slight increase in length. Subsequently, average wall tension (tensile stress) and intraluminal pressure declined, although deformation persisted. Between 6 h and 8 days after the onset of obstruction, intraluminal pressure remained essentially unchanged. During this time interval, ureteral deformation continued gradually and progressively as the ureter underwent creep both circumferentially and longitudinally. This was associated with a marked increase in average wall tension. At 8 days the diameter had increased by 170% and the length by 25%.


Biliary excretion of dye in dogs infused with BSP or its glutathione conjugate.

A comparison of the maximal rates of biliary excretion (Tm), of dye in dogs infused with either BSP or its glutathione conjugate (BSP-GSH) was carried out. Tm was much higher when BSP-GSH rather than BSP was infused. This was accounted for by a significantly higher concentration of dye in bile of dogs receiving BSP-GSH. Evidence is presented that BSP and its conjugated metabolites compete for a common transport carrier and that BSP disproportionately depresses the biliary excretion of conjugated dye compounds. This latter observation accounts for the depressed dye Tm found during infusion of BSP. Choleresis invariably accompanied dye excretion. When BSP-GSH was infused, enhanced bile flow could be accounted for by the predicted osmotic activity of dye transported into bile. By contrast, the choleresis measured during infusion of BSP was significantly greater than that predicted. An additional mechanism for choleresis is operative, therefore, when unconjugated BSP is infused. Administration of taurocholate enhanced dye Tm when BSP-GSH was infused. Since increments of canalicular bile flow induced by theophylline and glucagon did not enhance dye excretion into bile, this effect by taurocholate appears to be related to taurocholate excretion per se rather than to the enhanced canalicular bile flow which accompanies its excretion.


Vitamin K2 absorption by rat everted small intestinal sacs.

Small intestinal absorption of vitamin K2 was investigated in vitro. Experiments with increasing concentrations of the vitamin up to 900 nM revealed linerity between the concentration and the rate of absorption (r = 0.99). Addition of metabolic uncouplers and inhibitors such as 2,4-dinitrophenol, sodium azide, and potassium cyanide did not decrease the rate of absorption of the vitamin (P less than 0.05). Absorption rate of the vitamin increased when taurocholate was replaced by a nonionic detergent, Pluronic F-68. The addition of butyric and octanoic acids to the incubation solution caused an increase in the absorption rate of vitamin K2. No change in the absorption of the vitamin occurred in the presence of oleic and linoleic acid. Addition to vitamins K1 and K3 to the incubation solution did not change the rate of vitamin K2 absorption. These findings suggest that vitamin K2 is absorbed by the small bowel by a passive noncarrier-mediated diffusion process. The rate of diffusion varied when the lipid and bile salt composition of the incubation solution was modified. Distal intestinal absorption of vitamin K from bacterial sources coupled with colonic absorption of the vitamin may be the major constant source of vitamin K in mammals.


Effects of norepinephrine on mechanics of arteries in vitro.

The effects of smooth muscle activation on the pressure dependence of arterial wall characteristic impedance were studied with isolated segments of canine iliac and carotid arteries. Measurements of external diameter and transmural pressure were made before and after activation of the arterial smooth muscle (SM) by norepinephrine (NE) in concentrations of 0.5 and 5 mug/ml and used to compute values of characteristic impedance (Z0). In the absence of SM tone, values of Z0 for both arterial sites increased monotonically with transmural pressure. For the larger [NE], values of ZO exhibited a minimum at pressures of the order of 125 mmHg and increased for both larger and smaller values of pressure, For the smaller [NE], values of Z0 showed a similar pressure dependence but with a broader minimum. It is concluded that the previously demonstrated constancy of vascular impedance with changes in arterial pressure is at least the result of the presence of a tonic level of SM activation in conduit arteries.