Splanchnic and leg exchange of glucose, amino acids, and free fatty acids during exercise in diabetes mellitus. The influence of exercise on leg and splanchnic exchange of substrates was examined in eight insulin-dependent diabetics 24 h after withdrawal of insulin and in eight healthy controls studied at rest and after 40 min of bicycle ergometer exercise at 55-60% of maximal capacity. In four of the diabetic subjects, basal arterial ketone acid levels were 3-4 mmol/ liter (ketotic diabetics) and in the remainder, below 1 mmol/liter (nonketotic diabetics). ,ree fatty acid (FFA) turnover and regional exchange were evaluated with 14-C- labeled oleic acid. Leg uptake of blood glucose rose 13-18 fold during exercise in both the diabetics and controls and accounted for a similar proportion of the total oxygen uptake by leg muscles (25-28%) in the two groups. In contrast, leg uptake of FFA corresponded to 39% of leg oxygen consumption in the diabetic group but only 27% in controls. Systemic turnover of oleic acid was similar in the two groups. Splanchnic glucose output increased during exercise 3-4 fold above resting levels in both groups. In the diabetics, splanchnic uptake of lactate, pyruvate, glycerol, and glycogenic amino acids rose more than twofold above resting levels and was fourfold greater than in exercising controls. Total precursor uptake could account for 30% of the splanchnic glucose output in the diabetic group. In contrast, in the controls, total splanchnic uptake of glucose precursors was no greater during exercise than in the resting state and could account for no more than 11% of splanchnic glucose output. The augmented precursor uptake during exercise in the diabetics was a consequence of increased splanchnic fractional extraction as well as increased peripheral production of gluconeogenic substrates. The arterial glucagon concentration was unchanged by exercise in both groups, but was higher in the diabetics. In the diabetic subjects with ketosis in the resting state, exercise elicited a rise in arterial glucose and FFA, an augmented splanchnic uptake of FFA, and a 2-3 fold increase in splanchnic output of 3-hydroxybutyrate. Uptake of 3-hydroxybutyrate by the exercising leg rose more rapidly than splanchnic production, resulting in a fall in arterial levels of 3-hydroxybutyrate. It is concluded that (a) glucose uptake by exercising muscle in hyperglycemic diabetics is no different from that of controls; (b) splanchnic glucose output rises during exercise to a similar extent in diabetics and controls, while uptake of gluconeogenic substrates is markedly higher in diabetics and accounts for a greater proportion of total splanchnic glucose output; (c) exercise in diabetic patients with mild ketosis is associated with a rise in blood glucose and FFA levels as well as augmented splanchnic production and peripheral uptake of ketone bodies.


Control of proximal tubule fluid reabsorption in experimental glomerulonephritis. We have recently shown that in the early autologous phase of nephrotoxic serum nephritis (NSN) single nephron glomerular filtration rate is unchanged from values in normal hydropenic control rats, but that single nephron filtration fraction and efferent arteriolar oncotic pressure (piE) are reduced because of a marked reduction in the glomerular capillary ultrafiltration coefficient. The present study was undertaken to examine the influence of this decline in piE as well as the other known determinants of peritubular capillary fluid exchange on absolute proximal fluid reabsorption (APR) in NSN. The findings indicate that APR and proximal fractional reabsorption are reduced significantly in NSN, relative to values in a separate group of age and weight-matched normal hydropenic control rats studied concurrently. In addition to the measured decline in piE, efferent arteriolar plasma flow (Qe) and peritubular capillary hydraulic pressure (Pc) were found to increase significantly, while interstitial oncotic pressure, estimated from hilar lymph, was not significantly different from values in control rats. Using a mathematical model of peritubular capillary fluid uptake we found that, assuming that the capillary permeability-surface area product and interstitial hydraulic pressure are unchanged in NSN, the observed changes in piE and Pc are sufficient to offset the effect of the increase in QE, yielding a calculated reduction in APR of approximately 4 nl/min, in excellent agreement with the observed mean decline of 4.1 nl/min. These findings suggest that control of APR in NSN is mediated by the same factors that regulate APR under normal physiological conditions, namely, the imbalance of forces governing peritubular capillary uptake of isotonic reabsorbate.


Estimation of thyroxine and triiodothyronine distribution and of the conversion rate of thyroxine to triiodothyronine in man. Studies on peripheral metabolism of simultaneously administered 125-I-labeled L-thyroxine ([125-I]T4) and 131-I labeled L-trilodothyronine ([131-I]T3) were performed in five normal subjects, in four patients with untreated hypothyroidism, and in 3 hypothyroid patients made euthyroid by the administration of T4.  The fractional turnover rate (lambda 03) of thyroid  hormones irreversibly leaving the site of degradation and the volumes of pool 1 (serum V1) of pool (interstitial fluid, V2), and of pool 3 (all tissues, V3)were obtained by using a three-compartment analysis.  In addition to the turnover studies, the ratios for the in vivo T4 to T3 conversion were determined by paper chromatographic study in sera obtained 4, 7, and 10 daysafter the injection.  The rate (K12) of the extrathyroidal conversion of T4 to T3 was also estimated by the compartment analysis.  The T3 distribution volume (V3) of pool 3, in which T3 is utilized and degraded, was about 60% of totaldistribution volume (V=V1+V2+V3) in normal subjects, whereas only about 25% of the extrathyroidal T4 pool was in the intracellular compartment, indicating that T3 is predominantly an  intracellular hormone..


Effect of ketone infusions on amino acid and nitrogen metabolism in man. To evaluate the role of hyperketonemia in the hypoalaninemia and decreased protein catabolism of prolonged starvation, Na dl-beta-hydroxybutyrate was administered as a primed continuous 3-6-h infusion in nonobese subjects and  in obese subjects in the postabsorptive state and after 3 days and 3-5 1/2 wk of starvation. An additional obese group received 12-h ketone infusions on 2 consecutive days after 5-10 wk of fasting. The ketone infusion in nonobese and obese subjects studied in the postabsorptive state resulted in total blood ketone acid levels of 1.1-1.2 mM, a 5-15 mg/100 ml decrease in plasma glucose, and unchanged levels of insulin, glucagon, lactate, and pyruvate. Plasma alanine fell by 21% (P smaller than 0.001) in 3 h. In contrast, other amino acids were stable or varied by less than 10%. Infusions lasting 6 h reduced plasma alanine by 37%, reaching levels comparable to those observed in prolonged starvation. Equimolar infusions of NaC1 and/or administration of NaHCO3 failed to alter plasma alanine levels. During prolonged fasting, plasma alanine, which had fallen by 40% below prefast levels, fell an additional 30% in response to the ketone infusion. In association with repeated prolonged (12 h) infusions in subjects fasted 5-10 wk, urinary nitrogen excretion fell by 30%, returning to base line after cessation of theinfusions and paralleling the changes in plasma alanine. Ketone infusins resulted in two- to fourfold greater increments in blood ketone acids in fasted as compared to postabsorptive subjects. It is concluded that increased blood ketone acid levels induced by infusions of Na DL-beta-hydroxybutyrate result in hypoalaninemia and in nitrogen conservation in starvation. These data suggest that hyperketonemia may be a contributory factor in the decreased availability or circulating alanine and reduction in protein catabolism characteristic of prolonged fastings9


Chloramphenicol-containing drugs. A report from Spain. The composition of 185 Spanish compounds containing chloramphenicol, along with the information supplied in ther package inserts, were studied. Only 11 of these compounds contained chloramphenicol alone, this antibiotic being associated with other chemotherapeutic agents and/or other drugs in the remainder. Indications listed in the leaflet largely went beyond the limits of the medically established uses of chloramphenicol, and information concerning side effects, contraindications, or precautions was scanty and in some instances even confusing. A change in the availability of drug combinations containing chloramphenicol and an improvement of the information accompanying them is urged.


Neural intersegmental connection in the spinal root and ganglion region of the rat. A study has been made of the macroscopic, microscopic and electron-microscopical appearance of intersegmental neural connections in the rat. Macroscopically, spinal roots and ganglia of adjacent segments were frequently observed to be linked by discrete, slender strands, mainly in the lumbosacral region where the roots are long. When examined under the light microscope, even the smallest was found to contain as many as 72 myelinated fibres with a range of diameters between 1.5-14 mu-m. The were commonly accompanied by blood vessels. Connections, when present, contributed to as much as 6-28% of the total number of myelinated axons in dorsal roots. Under the electron microscope, links between dorsal roots, or between dorsal roots and adjacent ganglia, contained unmyelinated fibres comparable in numbers to those found in the dorsal roots themselves. In links between ventral roots and ganglia the numbers of unmyelinated fibres proportionally exceeded those found in ventral roots. The presence of these connections may account for the reported finding of undamaged nerve fibres in the dorsal roots after dorsal root sectioning or ganglionectomy and in the ventral roots after ventral root sectioning.


Effect of diethylenetriaminepentaacetic acid and procaine on hemorrhage induced by rattlesnake venom. Nineteen compounds and seven combinations of compounds were tested for their ability to neutralize the hemorrhagic activity of Crotalus atrox venom in vitro and in vivo. Two compounds and four combinations were effective in reducing hemorrhage in an in vivo test in which the venom was injected before injection of compounds. DTPA plus procaine HCl was the most effective combination and reduced hemorrhage when injected 1, 5, or 15 minutes after injection of venom. DTPA-procaine reduced hemorrhage induced by injection of C. atrox venom into dogs as well as mice. DTPA in combination with procaine did not reduce myonecrosis or lethality resulting from injection of venom into mice, but it could be used in conjunction with antivenin to treat local tissue damage resulting from rattlesnake venom poisoning.


The distribution of the olfactory tracts in the bullhead catfish, Ictalurus nebulosus. Using degeneration staining methods, central projections of the olfactory tracts in the bullhead catfish, Ictalurus nebulosus were studied. Seporate lesions were made of the lateral and medial olfactory tracts in an attempt to separate their zones of projection. Three major terminal fields were found: lateral, medial and central-posterior complex. Two additional minor projections were seen: interbulbar and hypothalamic. The lateral division of the olfactory tract terminates in lateral, central and hypothalamic terminal fields. The medial tract projects to lateral, meedial, posterior and hypothalamic fields. All terminal fields were found bilaterally; the lateral tract partly crossing in both the anterior commissure. A small intellbulbar commissure was also found to contain medial tract fibers. Evidence is given to show that the anterior olfactory nucleus, if present in catfish, may be located within the olfactory bulb itself. Similarities between mammalian and teleost olfactory systems are also discussed.


Pharmacokinetics of creatinine in man and its implications in the monitoring of renal function and in dosage regimen modifications in patients with renal insufficiency. A single-compartment model is proposed to describe the pharmacokinetics of creatinine in man. Based on the information from the literature, it was estimated that the average biological half-life of creatinine in normal male adults between 20 to 39 years old is 3.85 hours. This half-life is prolonged in renal patients and becomes 77 hours when renal function decreases to 5 per cent of normal. Based on pharmacokinetic analysis, it was also shown that the time required to reach a new steady-state serum creatinine level after onset of renal failure is highly dependent upon the degree of renal insufficiency. For example, for the subjects analyzed in this paper, it was estimated that it will take 1.1, 2.5, 6.7, and 13.4 days to reach 95 per cent of the steady-state levels when the renal function drops to 50, 25, 10, and 5 per cent of the normal capacity. The model analysis also predicts that from a practical point of view the daily fluctuation in serum level in patients with better than 25 per cent of normal renal function is not very significant. On the other hand, the fluctuation in the early stage of severe renal failure is predicted to be very dramatic. The analysis also predicts that the serum level will decrease to a normal or near normal value within two days after improvement of renal function from moderately to severely impaired state. The data obtained from an anuric patient seems to support the validity of the pharmacokinetic approach used in this study. The implications of the above pharmacokinetic analyses for the monitoring of renal function and dosage regimen modifications in patients with renal insufficiency were discussed.


Intense surveillance of adverse drug reactions. An analysis of 338 patients. A prospective study of adverse drug reactions was recently completed at the Clinical Pharmacology Unit of J. J. Group of Hospitals. 338 patients were included in this study, and adverse reactions were noted by a team of workers including a nurse and a physician. World Health Organization definitions were used to describe adverse reactions. A total of 20 per cent of the patients showed adverse reactions to drugs. There was no difference with regard to age, occupation, or religion of the patients. Reaction was more common in the undernourished and also with a larger number of drugs or longer duration of stay in the hospital. The common reactions were neurologic, gastrointestinal, and allergic. Significant information is obtained by analysis of the percentage reaction in patients receiving drugs and the percentage of reactions per doses administered. It is confirmed that short-term intense surveillance programs are capable of providing useful data on incidence and types of adverse drug reactions.


Pharmacokinetics of phenformin in man.

Pharmacokinetics of phenformin in man. Phenformin was assayed in urine, plasma, and sputum specimens, obtained from two healthy volunteers during the four-day period following oral administration of a single therapeutic dose. Approximately one third of the drug was excreted unchanged in the urine. Phenformin profiles were obtained for urinary excretion rates and for plasma and saliva concentrations. The terminal exponential declines indicate a half-life of approximately 11 hours. At 37 degrees C, plasma bound 19 per cent of added phenformin.


Intensity and pattern discrimination after lesions of the pretectal complex, accessory optic nucleus and ventral geniculate in pigeons. Pigeons were trained to discriminate between pairs of visual stimuli that differed in intensity or pattern. After completion of training, bilateral, stereotaxic lesions were made in various cell groups in the mesencephalon and diencephalon that receive terminals of the optic tract. The target regions were nucleus ectomamillaris (accessory optic nucleus), nucleus lentiformis mesencephali and area pretectalis (prectal complex) and the nucleus geniculatus lateralis, pars ventralis (ventral geniculate). In some cases, combined lesions of nucleus lentiformis mesencephali and area pretectalis were made. Lesions of nucleus ectomamillaris, nucleus lentiformis mesencephali, area pretectalis, or ventral geniculate did not produce major impairments of discrimination performance nor did combined lesions of nucleus lentiformis mesencephali and area pretectalis. A number of cases of intended destruction of the ventral geniculate also had extensive damage of the overlying nucleus rotundus. In several of these cases of combined destruction of nucleus rotundus and ventral geniculate, the previously reported discrimination deficits following nucleus rotundus lesions did not appear. In those cases in which the nucleus rotundus deficit was observed, the lesions were found to include the nucleus subpretectalis, which, like nucleus rotundus, receives tectofugal fibers via the brachium of the superior colliculus. The data of the ventral geniculate + rotundus cases and ventral geniculate + rotundus + subpretectalis cases suggest that sensory deficits following a lesion in a particular cell group may not necessarily indicate that the sensory information is processed in that cell group, but rather that the lesion had deprived other cell groups of the appropriate input necessary for their proper functioning.


The differential projections of the olfactory bulb and accessory olfactory bulb in mammals. Three species were studied, the rabbit, opossum and rat. Lesions of the main olfactory bulb caused terminal degeneration, assayed by the Fink-Heimer method, to occur in the ipsilateral olfactory tubercle, prepyriform cortex (including its periamygdaloid part), ventrolateral entorhinal area, and in anterior and posterolateral divisions of the cortical amygdaloid nucleus. The various parts of the ipsilateral anterior olfactory nucleus and the rostroventral end of the anterior continuation of the hippocampus (hippocampal rudiment) also received this projection. Lesions of the accessory olfactory bulb, which receives its sensory input from the vomeronasal (Jacobson's) organ, caused terminal degeneration to occur in the medial amygdaloid nucleus and in a posteromedial part of the cortical amygdaloid nucleus. This projection was conveyed by an accessory olfactory tract, which is accompanied in part of its course by a small nucleus, the bed nucleus of the accessory olfactory tract. The accessory olfactory tract is initially a part of the lateral olfactory tract but becomes increasingly indivuated at more posterior levels. It parts company with the lateral olfactory tract at the rostral end of the amygdaloid region, and, in addition to distributing to the medio-cortical amygdaloid region, it enters the stria terminalis to terminate in the bed nucleus of the stria terminalis in a small region bearing cytoarchitectonic resemblance to the medial amygdaloid nucleus. The topographic segregation of the areas of termination of the olfactory and accessory olfactory (vomeronasal) projections is suggestive of a functional dichotomy in the organization of the olfactory system...


Crossed pathways from the entorhinal area to the fascia dentata. I. Normal in rabbits. The entorhinal area projects to the Ammon's horn and the fascia dentata by way of the medial and lateral perforant paths that originate in the medial and lateral part of that area, respectively. The two tracts terminate at different laminar levels in the molecular layers of the ipsilateral hippocampal regio inferior and fascia dentata. Using the Fink-Heimer technique, each of the perforant paths in the normal rabbit is now shown to innervate the antero-dorsal extremes of the Ammon's horn and fascia dentata in both hemispheres. The crossed and uncrossed components of each path innervate homotopic zones on each side. This bilateral innervation contrasts with the situation in the rat where only very weak crossed components exist. Degeneration particles in the fascia dentata contralateral to a lesion of the perforant paths diminish in number along the course of the fibers as they proceed away from the midline, but are traceable for several millimeters. Crossed fibers are shown to pass from one hemisphere into the other directly through the fused molecular layers of the fasciae dentatae. The bilateral innervation in the rabbit indicates that even though the axons of the perforant paths are highly specific with respect to the class of neuron and the dendritic segments upon which they form synapses, they apparently do no possess a mechanism by which they can distinguish between the receptive fields in the two hemispheres. It is concluded that during ontogeny the perforant path fibers from both sides most likely compete for available synaptic sites in the rostral part of their terminal fields and that their relative amounts in the two hemispheres is governed by spatial and temporal factors.


Crossed pathways from the entorhinal area to the fascia dentata. II. Provokable in rats. In the rat thhe perforant pathways from the entorhinal area normally innervate the fascia dentata only ipsilaterally. However, unilateral ablation of the entorhinal area (deentorhination) induces the formation of an anomalous crossed projection from the intact contralateral entorhinal area to the septal portion of the deafferented fascia dentata. After deentorhination of rats aged 1-30 days the organization of this projection was analyzed (a) by producing secondary lesions in the intact entorhinal area of perforant paths and observing the results anterograde degeneration with Fink-Heimer silver impregnation techniques, and (b) by staining with Timm's sulfide silver method whichmakes the terminal fields of afferent systems stand out in different tones of colors. Both methods showed the crossed entorhino-dentate projection to consist of two separable components. They were named the crossed medial perforant path and the crossed lateral perforant path, corresponding to their similarity in origin, dendritic localization of termination and Timm stainability to the ordinary, uncrossed medial and the lateral perforant pathways (MPP and LPP) which arise in the medial and lateral parts of the entorhinal cortex, respectively. Similarly induced crossed projections were demonstrated to the subcallosal continuation of fascia dentata, the fasciola cinerea. The heaviest terminal field of the crossed entorhino-dentate projection which was found in the most rostral and medial parts of the deafferented fascia dentata correlated with a lack of expected aberrant extension into theMPP and LPP  terminal zones of commissural and ipsilateral hippocampodentate fibers. In Fink-Heimer preparations there was little variation in the distribution of the aberrant crossed sustems over the range of ages studied although the chronic operations performed earliest postnatally (5 days) tended to produce the heaviest representation. This latter observation appeared consistent with changes in the Timm staining pattern of the deafferented fascia dentata, since with an increase in age at the primary lesion from 5 to 14 days there was no increase in the spread into the fascia dentata of Timm stainable axon ter minals from CA3, interpreted as a sign of fewer crossed entorhinal afferents succeeding in a presumable competition with the CA3-derived system for available terminal space.


Distribution of ultrastructural tracers in crustacean axons. Ruthenium red and horseradish peroxidase were used to compare the uptake of exogenous molecules into crayfish motor axons and their sheaths in severed and intact peripheral nerves. Both tracers penetrated the axonal sheath and were subsequently seen lining small vesicles and tubules in the axoplasm. Tracer appeared to enter the axon via pinocytotic vesicles. There were no perceptible quantitative or qualitative differences in ruthenium red uptake between intact and severed axons. However, counts of tracer-filled vesicles in axons exposed to peroxidase showed that at least three times as much tracer penetrated the severed as opposed to the intact axons.


Genetically-associated variations in the development of reflex movements and synaptic junctions within an early reflex pathway of mouse spinal cord. The embryonic development of reflex forelimb movements produced by cutaneous stimulation of the forepaw was examined in five inbred strains of the house mouse, Mus musculus. A quantitative electron microscopic study of synapse formation between the neurons that comprise the spinal cutaneous reflex arc was also carried out on specimens from three of the strains subjected to reflex testing. This investigation provides evidence that there is significant genetically-associated variability in the developmental timing of synapse formation within this disynaptic pathway and in the reflex behavior which it mediates. Specifically, it was found that C57BL/6J embryos had greater numbers of synaptic junctions in the reflex pathway at embryonic days 14-16, and they also showed reflex movements earlier than LP/J embryos. C57BL/6J embryos also showed a more rapid increase in the number of boutons during this embryonic period. CBA/CaJ embryos displayed a temporal pattern of development that differed from both C57BL/6J and LP/J. At E15, CBA/CaJ embryos were more similar to LP/J with regard to both reflex activity and synapse number, but by E16, CBA/CaJ values for both of these measures were more similar to C57BL/6J. On the basis of the data detailed in the text, we suggest that the strains differ in the following manner: C57BL/6J embryos develop boutons rapidly but appear to be relatively inefficient in the actual formation of synaptic junctions; CBA/CaJ embryos develop boutons at a slower rate than C57BL/6J but form synaptic junctions more efficiently; LP/J embryos develop boutons slowly and are also relatively inefficient in forming synaptic junctions. The genetic implications of--and some developmental processes which might be responsible for--the observed strain differences in the timing of synaptic development are discussed in the text. There was no detectable genetic variability of the basic sequence in which the neurons of the cutaneous reflex arc develop their synaptic connections. For all three strains examined, the data indicated that synaptic closure occurred in a retrograde sequence with respect to the direction that neurotransmission normally flows between the neurons of this pathway. This finding agrees with results obtained by other investigators from a number of diverse vertebrate species, and such a widespread lack of variability implies that a retrograde sequencing of synapse formation is involved in the development of specific neuronal connectivities.


Surface fine structure of supraependymal elements and ependyma of hypothalamic third ventricle of mouse. The ependymal surface of the hypothalamic third ventricle of the adult female and male mouse was examined with the scanning electron microscope. The material was dried with the critical point method. Supraependymal cells, exhibiting a variety of forms, lie among the cilia of the rostrodorsal two-thirds of the ventricle. The cell bodies are usually between 8 and 10 mu in diameter and have dividing pseudopodial processes which may be broad or narrow, flat or stout, smooth or varicosed. The textured surfaces of the cells seen in this material appear to have no cilia, microvilli or membraneous folds though they may have small bleb-like protrusions. Some cells and adjacent cilia bear clusters of friable-looking material that may be secretory. In several female mice, mounds of debris, that could be degenerating cells or secretory material, were seen in intimate association with clusters of cells. The cells' processes extend over and through the surface of the mound. While some supraependymal cells may be neurons or glia, it is suggested that many of the cells seen may be morphological variants of one cell line, mononuclear phagocytes. Sausage-shaped structures at the end of long cilia-like stalks are described and their possible identity discussed.


The representation of the visual field in the lateral geniculate nucleus of Macaca mulatta. Microelectrode recording techniques were used to investigate the projection of the visual field into the lateral geniculate nucleus (LGN) of Macaca mulatta. The data were used to construct charts plotting visual direction, designated in terms of azimuth and elevation, onto sections of the nucleus cut in coronal, sagittal and horizontal Horsley-Clarke planes. The projection of the horizontal meridian divides the LGN along its plane of symmetry into a medial-superior half having negative elevations and a lateral-inferior half having positive elevations. Elevations become more positive or negative with distance from this plane. Azimuths closest to the vertical meridian are located posteriorly, while the most peripheral azimuths are found at the anterior pole. Two families of surfaces representing visual directions of constant azimuth and elevation are described. Visual field zones of increasing eccentricity are represented serially along the posterior-anterior axis of the LGN, with the foveal area restricted to the posterior pole and the monocular crescent projecting to the anterior pole. The mapping is completely continuous across the horizontal meridian. The edges of the stacked cell laminae exposed around the periphery of the LGN form an oval band which receives the projection of the perimeter of the contralateral hemifield. The vertical meridian is represented by the posterior two-thirds of this band, while the periphery of the hemifield projects to the anterior third. The central visual field out to the optic disc is represented by six cell layers, while the rest of the binocular field projects to four layers only (2 parvocellular and 2 magnocellular). The monocular crescent is represented by one parvocellular and one magnocellular layer. Features associated with the projection column of the optic disc are integrated into the transition from six to four layers. Details of the receptive field topography in the vicinity of the optic disc discontinuities indicate that these gaps are produced by intralaminar mechanisms. The magnification factor (mm-3/steradian) increased monotonically from peripheral visual fields to the foveal center, varying over a range of three decades. This range is intermediate between those derived from data reported in the literature for the retina and the striate cortex. The ratio of LGN magnifications at any two angular eccentricities is a power function, with an exponent of 1.34, of the corresponding ratio of retinal ganglion cell densities. Similarly, the ratio of cortical magnifications (mm-2/steradian) at any two eccentricites is a power function, with an exponent of 1.35, of the corresponding ratio of LGN magnifications.


The fine structure of pulse labeled (3-H-thymidine cells) in degenerating rat optic nerve. The ultrastructure of pulse labeled (3-H-thymidine) cells in rat optic nerve undergoing Wallerian degeneration is described. The study was limited to the first ten days after enucleation since cell proliferation during this interval is greater than in normal optic nerve (Skoff and Vaughn, '71). Approximately one-third of the pulse labeled cells are astrocytes. The majority of the proliferating astrocytes are in a reactive state, having changed their normal fibrous appearance to one showing a paucity of filaments. Thirty percent of the pulsed cells can be classified as microglia. Only immature oligodendrocytes proliferate, and they account for less than 10% of the pulse labeled cells. About 30% of the labeled population are undifferentiated glial precursor cells. Electron microscopic autoradiographic data obtained from normal optic nerve and presented in this paper indicates that glial precursor cells which have divided shortly before enucleation continue to proliferate after it. The evidence suggest that recently formed glial precursor cells transform into phagocytes following enucleation. Less than 3% of the pulse labeled cells examined in this study are ultrastructurally similar to mononuclear leukocytes. The results of the present study together with previous studies of degenerating optic nerve indicate that most phagocytes in Wallerian degeneration are derived from proliferation of intrinsic glia rather than from an invasion of exogenous cells.


Genetic mechanisms controlling the domestication of a wild house mouse population (Mus musculus L.). A controlled reenactment of the domestication process provided information on the relative effects of natural selection, inbreeding, and habitat upon an originally wild house mouse population. Effects were assessed by testing offspring that were bred under either laboratory or simulated natural conditions, systematically inbred or outbred, and postnatally fostered in laboratory or simulated natural habitats. Ten generations of domestication failed to reveal any behavioral differences due to either natural selection or habitat on nine different behavioral tests. Inbreeding strongly reduced intermale aggression, partially reduced resistance to recapture by humans, but failed to affect any of the seven other behaviors.


Interrelationship among multiunit activity of the midbrain reticular formation and lateral geniculate nucleus, thalamocortical arousal, and behavior in rats. Analyses of multiunit activity of midbrain reticular formation (RF) and lateral geniculate nucleus (LG) revealed marked phasic covariation that conformed to characteristics of behavior. Movement patterns appeared to set the range within which RF activity and thalamocortical arousal (as reflected in LG activity) varied. In tests of spontaneous behavior, sensory stimulation, bar pressing for food, and conditioned emotional response. RF activity and thalamocortical arousal conformed to immediate properties of behavior apart from conditions giving rise to the behavior. Other analyses revealed close relationships between RF activity and visual evoked response, but only a general relationship to hippocampal slow-wave rhythms. Our findings emphasize the necessity for refining psychological conceptualizations of arousal processes.


Effects of posterior parietal and frontal neocortical lesions in the squirrel monkey. Brightness discrimination, three forms of a spatial pattern discrimination in which the essential cue and site of reinforcement were separated (SSP), delayed response, form discrimination, and three forms of a spatial pattern discrimination in which the essential cue and site of reinforcement were identical (ISP) were given, in the order mentioned, to two groups of squirrel monkeys with frontal lesions were impaired on delayed response, and those with parietal lesions were impaired on form and SSP discriminations. Neither group was impaired on brightness discrimination. The results confirm and extend previous findings by other investigators that the posterior parietal cortex of nonhuman primates is critically involved in visually guided spatial discriminations when the primary cue and the site of reinforcement are separated.


Avoidance by rats of illumination with low power nonionizing electromagnetic energy. Rats spent more time in the halves of shuttle boxes that were shielded from illumination by 1.2 GHz microwave energy than in the unshielded. In Experiment 1, rats avoided the energy when it was presented as 30-musec pulses with a pulse repetition rate of 100 pulses per second (pps). The average power density was about .6 mW/cm2, and the peak power density was about 200 mW/cm2. In Experiment 2, the energy was presented both continuously and in pulse-modulated form, i.e., .5-msec exponentially decaying pulses at a rate of 1,000 pps. The average power density of the continuous energy was 2.4 mW/cm2, and the average power density of the pulse-modulated energy was .2 mW/cm2. The peak power density of the modulated energy was 2.1 mW/cm2. The rats avoided the pulsed energy, but not the continuous energy.