Relations among transepithelial sodium transport, potassium exchange, and cell volume in rabbit ileum. The relation between active transepithelial Na transport across rabbit ileum and 42K exchange from the serosal solution across the basolateral membranes has been explored. Although 42K influx across the basolateral membranes is inhibited by ouabain and by complete depletion of cell Na, it is not affected when transepithelial Na transport is abolished (i.e. in the presence of an Na-free mucosal solution) or stimulated (i.e. when glucose or alanine is added to the mucosal solution). We are unable to detect any relation between the ouabain-sensitive Na-K exchange mechanism responsible for the maintenance of intracellular Na and K concentrations and active transcellular Na transport. In addition, the maintenance of cell volume (water content) does not appear to be dependent upon transepithelial Na transport or the ouabain-sensitive Na-K exchange pump. Although the results of these studies cannot be considered conclusive, they raise serious questions regarding the role of the Na-K exchange pump, located at the basolateral membranes, in active transepithelial Na transport and the maintenance of cell volume.


The involvement of gamma-aminobutyric acid in the organization of cat retinal ganglion cell receptive fields. A study with picrotoxin and bicuculline. The effects of picrotoxin and bicuculline upon the discharge pattern of center-surround organized cat retinal ganglion cells of X and Y type were studied. All experiments were carried out under scotopic or possibly low mesopic conditions; mostly but not exclusively on-center cells were studied. Stimuli were chosen so that responses were either; (a) "purely" central; (b) surround dominated; or (c) clearly mixed but center dominated. In each case a pre-drug control response was estaboished, the drug was administered intravenously, and its subsequent effect upon the response was observed. In Y cells both picrotoxin and bicucullin caused the center-driven component of the response to become somewhat reduced in magnitude, while the surround component was substantially reduced. There was thus a change in center-surround balance in favor of the center-driven component. Responses of X cells remained virtually unaffected by both picrotoxin and bicuculline.


Electromechanical properties of the single cell-layered heart of tunicate Boltenia ovifera (sea potato). The tubular heart of the sea potato is composed of a single layer of myoepithelial cells interconnected near the extraluminal surface by specialized junctions. If these junctions are used as the border which separates the luminal from extraluminal membrane, the surface area ratio, luminal:extraluminal, is approximately 12:1. A single myofibril is located near the luminal surface in each cell. Current passed across the heart wall in the direction that depolarizes the luminal membrane and hyperpolarizes the extraluminal membrane immediately produces "all-or-none" action potentials and contractions. Current passed in the opposite direction fails to produce action potentials until after the break of the stimulus, suggesting anodal break excitation of the hyperpolarized luminal membrane. High potassium solutions depolarized the myoepithelium and produced contractions only when applied to the luminal surface of the heart. [Ca]0 increases and [Mg]0 decreases twitch tension only on the luminal surface of the heart. The transwall resistivity is low (50-100 omega/cm2) due to an extracellular shunt. Because of this shunt and the larger surface area of the luminal membrane, the extraluminal membrane is effectively clamped to the potential of the luminal membrane and is not capable of directly influencing excitation-contraction coupling. These findings suggest that only the luminal membrane of the sea potato myoepithelium is capable of generating an action potential and triggering contraction.


Dynamics of aminopyridine block of potassium channels in squid axon membrane. Aminopyridines (2-AP, 3-AP, and 4-AP) selectively block K channels of squid axon membranes in a manner dependent upon the membrane potential and the duration and frequency of voltage clamp pulses. They are effective when applied to either the internal or the external membrane surface. The steady-state block of K channels by aminopyridines is more complete for low depolarizations, and is gradually relieved at higher depolarizations. The K current in the presence of aminopyridines rises more slowly than in control, the change being more conspicuous in 3-AP and 4-AP than in 2-AP. Repetitive pulsing relieves the block in a manner dependent upon the duration and interval of pulses. The recovery from block during a given test pulse is enhanced by increasing the duration of a conditioning depolarizing prepulse. The time constant for this recovery is in the range of 10-20 ms in 3-AP and 4-AP, and shorter in 2-AP. Twin pulse experiments with variable pulse intervals have revealed that the time course for re-establishment of block is much slower in 3-AP and 4-AP than in 2-AP. These results suggest that 2-AP interacts with the K channel more rapidly than 3-AP and 4-AP. The more rapid interaction of 2-AP with K channels is reflected in the kinetics of K current which is faster than that observed in 3-AP or 4-AP, and in the pattern of frequency-dependent block which is different from that in 3-AP or 4-AP. The experimental observations are not satisfactorily described by alterations of Hodgkin-Huxley n-type gating units. Rather, the data are consistent with a simple binding scheme incorporating no changes in gating kinetics which conceives of aminopyridine molecules binding to closed K channels and being released from open channels in a voltage-dependent manner.


Effect of verapamil and of extracellular Ca and Na on contraction frequency of cultured heart cells. Monolayer cultures of myocardial cells were prepared by trypsin dispersion of neonatal rat ventricles. The cells were cultured for 4-5 days by which time a synchronously contracting monolayer of some 1.0 x 10(6) cells per 6-cm diam petri dish had formed. The contraction frequency and Na influx of the cells were unaffected by tetrodotoxin (2 x 10(-5) mg/ml) but both were markedly reduced by the addition of verapamil (10(-9) M to 10(-5) M). The effect of verapamil on both parameters occurred very rapidly. Although unresponsive to change in [Ca]0 between 0.3 mM and 3.0 mM, the contraction frequency of the cells declined rapidly as the [Ca]0 was reduced below 0.3 mM. On the other hand the beating rate of the cells was linearly related to [Na]0 below 40 mM the cells ceased to contract. It is therefore apparent that both [Ca]0 and [Na]0 contribute to the maintenance of the contraction frequency of cultured myocardial cells, but the latter is by far the more important. There also appeared to be, under all conditions, a close relationship between verapamilsensitive Na influx and contraction frequency. For the greater part this relationship was linear although at higher Na influx values it appeared to show evidence of saturation.


Permeability of the sodium channel in Myxicola to organic cations. The relative permeability of sodium channels to organic cations was determined in the Myxicola giant axon. Ionic currents under potential control were measured in seawater and in sodium-free solutions containing the organic cation. The measured reversal potential and the Goldman equation were used to obtain the relative permeabilities. The permeability sequence was found to be: sodium greater than hydroxylamine greater than hydrazine greater than ammonium greater than guanidine greater than formamidine greater than aminoguanidine greater than methylamine. Measurements were also made on sodium and several of the organic cations at different concentrations. The relative permeabilities of the ions were found to be independent of concentration. Qualitatively, the permeability sequence for the Myxicola giant axon was similar to that of the frog node of Ranvier.


Furosemide inhibition of chloride transport in human red blood cells. The chloride self-exchange flux across the human red cell membrane is rapidly and reversibly inhibited by 10(-4) M furosemide, a potent chloruretic agent. Furosemide reduces the chloride flux at all chloride concentrations and increases the cellular chloride concentration at which the flux is half-maximum. Kinetic analysis of the flux measurements made at several furosemide and chloride concentrations yields a pattern of mixed inhibition with a dissociation constant for the inhibitor-transport mechanism complex of 5 X 10(-5) M. From this pattern of inhibition and other observations, including that the percent inhibition is independent of pH (range 5.6-8.9), we conclude that the anionic form of furosemide interacts primarily with the chloride transport mechanism at a site separate from both the transport site and the halide-reactive modifier site.


Kinetics of bicarbonate-chloride exchange across the human red blood cell membrane. The kinetics of bicarbonate-chloride exchange across the human red cell membrane was studied by following the time course of extracellular pH in a stopped-flow rapid-reaction apparatus during transfer of H+ into the cell by the CO2 hydration-dehydration cycle, under conditions where the rate of the process was determined by HCO3--Cl- exchange flux across the membrane. The flux of bicarbonate increased linearly with [HCO3-] gradient from 0.6 to 20 mM across the red cell membrane at both 37 degrees C and 2 degrees C, and decreased as transmembrane potential was increased by decreasing extracellular [Cl-]. An Arrhenius plot of the rate constants for the exchange indicates that the Q10 is strongly dependent on temperature, being about 1.7 between 24 degrees C and 42 degrees C and about 7 between 2 degrees C and 12 degrees C. These data agree well with the published values for Q10 of 1.2 between 24 degrees C and 40 degrees C and of 8 between 0 degrees C and 10 degrees C. The results suggest that different processes may determine the rate of HCO3--Cl- exchange at low vs. physiological temperatures, and that the functional (and/or structural) properties of the red cell membrane vary markedly with temperature.


Length-dependent electromechanical coupling in single muscle fibers. In single muscle fibers from the giant barnacle, a small decrease in muscle length decreases both the calcium activation and the peak isometric tension produced by a constant current stimulus. The effect is most pronounced if the length change immediately precedes the stimulation. In some cases, the decrease in tension with shortening can be accounted for almost entirely by a decrease in calcium release rather than changes in mechanical factors such as filament geometry. During the constant current stimulation the muscle membrane becomes more depolarized at longer muscle lengths than at the shorter muscle lengths. Under voltage clamp conditions, when the membrane potential is kept constant during stimulation, there is little length dependence of calcium release. Thus, the effect of length on calcium release is mediated through a change in membrane properties, rather than an effect on a subsequent step in excitation-contraction coupling. Stretch causes the unstimulated fiber membrane to depolarize by about l mV while release causes the fiber membrane to hyperpolarize by about the same amount. The process causing this change in potential has an equilibrium potential nearly 10 mV hyperpolarized from the resting level. This change in resting membrane potential with length may account for the length dependence of calcium release.


Mechanisms of resistance to fusidic acid in Staphylococcus aureus. The biochemical mechanisms of resistance to fusidic acid in Staphylococcus aureus were investigated. Organisms possessing plasmid genes for resistance showed a high basal level of resistance, but could be induced to higher levels after pre-incubation with fusidic acid. This induction occurred rapidly and probably did not depend on gene dosage effects. Mutants resistant to fusidic acid, obtained from plasmid-negative cultures, expressed resistance constitutively. Protein synthesis in cell-free extracts from staphylococci with plasmid-mediated resistance to fusidic acid was as sensitive to fusidic acid as was synthesis in preparations from sensitive organisms; whereas protein synthesis in preparations from a spontaneous fusidic acid resistant mutant was resistant to the antibiotic. None of the resistant strains caused detectable inactivation of fusidic acid and no new derivative of fusidic acid was found in culture extracts of plasmid-possessing organisms grown in the presence of radioactive antibiotic. Expression of plasmid-mediated resistance to fusidic acid was associated with a decrease in the molar ratio of phosphatidylglycerol to lysylphosphatidylglycerol, but the cardiolipin content remained constant.


Nitrate reductase from anaerobically grown Rhizobium japonicum. The activity of nitrate reductase in Rhizobium japonicum is controlled by oxygen tension, and not by nitrate. The enzyme from R. japonicum grown anaerobically in the presence of nitrate resembles that from bacteroids in having a molecular weight of about 69000 daltons; the enzyme from aerobically grown cells ahs a molecular weight of about 170000 daltons. Both types of enzyme have similar Km values, but differ in their sensitivity to KCN.


Actinorhodin is a chromosomally-determined antibiotic in Streptomyces coelicolar A3(2). Streptomyces coelicolar A3(2) synthesizes a second antibiotic, in addition to the plasmid-determined methylenomycin A. It was identified, primarily on the evidence of mass spectroscopy of its diethyl ester, as actinorhodin, which has been described previously in other strains. It inhibited most Gram-positive bacteria tested, but only at a comparatively high concentration. Five independent mutations leading to lack of actinorhodin synthesis were located between cysD and strA on the chromosome.


Regulation of growth of Acinetobacter calcoaceticus NCIB8250 on benzyl alcohol in batch culture. Formation of benzoate and catechol during oxidation of benzyl alcohol by washed suspensions of Acinetobacter calcoaceticus NCIB8250 confirmed earlier results indicating that this organism metabolizes benzyl alcohol via benzaldehyde, benzoate, and the 3-oxoadipate pathway. There was no evidence for feedback inhibition of benzyl alcohol dehydrogenase or benzaldehyde dehydrogenase II. Examination of growth curves and patterns of substrate utilization, as well as measurement of enzyme activities, showed that benzyl alcohol dehydrogenase and benzaldehyde dehydrogenase II are repressed when A. calcoaceticus utilizes L-mandelate or phenylglyoxylate. Growth of bacteria on L-mandelate prior to their inoculation into benzyl alcohol/salts medium leads to an exceptionally long lag period before benzyl alcohol is used at the maximum rate. Benzyl alcohol metabolism is also suppressed during growth on benzoate.


Properties of phage-receptor lipopolysaccharide from Pseudomonas morsprunorum. Lipopolysaccharide (LPS) of Pseudomonas morsprunorum was extracted with hot phenol and purified by repeated centrifuging followed by either block electrophoresis or gel filtration. LPS from a virulent isolate exhibited specific phage inactivation (PI50 = 0.05 mug LPS ml-1), whereas LPS from an avirulent phage-resistant mutant did not. LPS was considered pure when a single band was detected following sodium dodecyl sulphate-cellulose acetate electrophoresis (pH 7.4). It was not phytotoxic when inoculated into cherry leaves at concentrations up to I mg ml-1, but produced weak chlorosis in bean and tobacco at 2 mg ml-1: no visible symptoms appeared after treatment with lower concentrations. The chemical composition of the LPS was partly determined.


Some aspects of the metabolism of butyrivibrio fibrisolvens. The growth responses of an acetate-utilizing isolate of Butyrivibrio fibrisolvens to CO2, acetate and pyruvate were determined using a chemically-defined medium. Carbon dioxide was essential for growth and both acetate and pyruvate increased growth. 14C from [I-14C]pyruvate appeared predominantly in formate and lactate. These results, together with those obtained with enzyme preparations, indicated pyruvate synthase, pyruvate-CO2 exchange and pyruvate formate lyase to be active.


Leucosporidium yeasts: obligate psychrophiles which alter membrane-lipid and cytochrome composition with temperature. The temperature limits of growth of three psychorphilic yeasts, Leucosporidium frigidum, L. gelidum and L. nivalis, were examined. All species grew well as subzero temperatures (-I degrees C). The maximum temperature of growth was significantly higher with glucose as substrate (18 to 20 degrees C) than with ethanol (17 to 18 degrees C). There was a positive correlation between the growth temperature and the degree of fatty-acid unsaturation of the cell lipids; the lower the temperature, the greater the degree of fatty-acid unsaturation. At subzero temperatures (-I degrees C) with ethanol as substrate, 90% of the total fatty acid was unsaturated with linolenic (35 to 50%) and linoleic (25 to 30%) acids predominating. At temperatures close to the maximum for growth, linolenic acid accounted for less than 20% of the total fatty acid and oleic (20 to 40%) and linoleic (30 to 50%) acids were the major components. Difference spectra of intact cells showed marked changes in the rations and amounts of individual cytochromes as a function of growth temperature. In L.frigidum with glucose as substrate, the ratios of cytochromes a +a3:b:c at 8 and 19 degrees C were I:I-I:2-9 and I:2-3:16-7 respectively. Similar changes in cytochrome ratios were noted for L.gelidum, but changes were much less marked for L. nivalis. The temperature effects were interpreted as supporting the view that membrane structure and composition are fundamental to temperature adaptation in psychrophilic yeasts.


Isolation of pigmentation mutants of Pseudomonas phenazinium. Pigmentation mutants of Pseudomonas phenazinium unable to synthesize iodinin, or producing it only in reduced amounts, were isolated. The abilities of the mutants to synthesize nine other phenazines were also altered. Cross-feeding experiments and the altered patterns of pigment production suggested metabolic relationships between the phenazine pigments, and a scheme for their biosynthesis is proposed.


Fermentation of purines and their effect on the adenylate energy charge and viability of starved Peptococcus prévotii. The principal products of endogenous metabolism of the obligate anaerobe Peptococcus prévotii were carbon dioxide, ammonia, acetate and butyrate, which are also produced by fermentation of nucleosides, purines and ribose, thus supporting our previous finding that RNA is the only cellular component to undergo substantial degradation under starvation conditions. Minor products were hydrogen, formate and propionate. The stoicheiometries of fermentation of xanthine, adenine, adenosine and ribose were determined. The ability to ferment exogenous nucleosides, purines and ribose declined rapidly on starvation, as did the ability to generate ATP from xanthine, and was paralleled by the loss of viability. However, addition of pulses of xanthine or adenine to organisms in the early stages of starvation sustained their adenylate energy charge and prolonged their viability. Evidence suggests that P. prévotii dies when its principal energy source (RNA) is depleted, and a possible explanation is that the transport function of the cytoplasmic membrane decays rapidly under these conditions so that, on transfer to a recovery medium, uptake of nutrients is inadequate to support growth.


Identification of glucitol (sorbitol) and ribitol in a rust fungus, Puccinia graminis f. sp. tritici. An examination of the soluble carbohydrates of the wheat stem rust fungus, Puccinia graminis Pers. f. sp. tritici Erikss. & E. Henn., showed the presence of glucitol (sorbitol), ribitol, fructose, and traces of xylitol, as well as confirming the presence of minnitol, arabitol, trehalose, inositol and erythritol. Ribitol and glucitol were major components in glucose-grown mycelium, and appeared to be the major components in mycelium parasitic on wheat leaves, but not in germinated or ungerminated uredospores. It is suggested that glucitol and ribitol may be intermediates (or by-products) of glucose utilization, whereas mannitol, arabitol and trehalose represent storage carbohydrates.


Examination of the polypeptides of hepatitis B surface antigen. When the polypeptides of hepatitis B surface antigen were examined by SDS-polyacrylamide gel electrophoresis under a variety of conditions, anomalous results were found to be due to (i) variable and at times incomplete dissociation of polypeptides after boiling with 1% SDS and reducing agent, (ii) reaggregation of solubilized material under certain electrophoretic conditions and during laboratory manipulations, and (iii) the variable presence of additional components in hepatitis B surface antigen prepared from certain individual donors. When these factors were taken into account, two major components were consistently identified by discontinuous buffer polyacrylamide gel electrophoresis, of apparent mol. wt. 60000 to 70000 and 12000 to 14000. However, in view of the demonstrated limitations of this technique in examining HBsAg polypeptides, alternative methods are necessary to confirm the true mol. wt. of the unique virus-specified amino acid sequence present.


Determination of conjugated monoamine metabolites in brain tissue. Levels of free and conjugated monoamine metabolites were analysed in brain tissue of rat and man. In the rat the conjugates were mainly of the sulfate ester type. The levels of conjugated dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) constituted 40--50% of the total amount of the metabolites. 4-Hydroxy-3-methoxy-phenylglycol (HMPG) and 5-hydroxy-3-indoleacetic acid (5-HIAA) were present as conjugates in 90 and 10% of the total levels. Chlorpromazine treatment resulted in an elevation of both the free and the conjugated forms of the dopamine metabolites and HMPG. In a human caudate nucleus obtained at autopsy both DOPAC and HMPG were present in the free form and as sulfate and glucuronide conjugates. The major dopamine metabolite found in this human brain was HVA. This metabolite and 5-HIAA occurred predominantly as free metabolites.


A rapid and simple micromethod to measure picograms of norepinephrine (NE) and dopamine (DA) in small samples of brain tissue and pituitary gland. A rapid and simple procedure to determine Dopamine (DA) and Norepinephrine (NE) in small tissue samples (mug quantities) is described. The radioenzymatic assay sensitivity, defined as twice the blank, is about 0.1 ng for NE and DA. Drugs known to modify brain catecholamine metabolism were shown to alter differentially DA and NE concentration in the medial basal hypothalamus (MBH) of male rats. Different areas of the brain and the pituitary gland, namely the parietal cortex, the pre-optic region (POA), the median eminence (ME), the medial basal hypothalamus without the median eminence and the posterior pituitary contain different concentrations of DA and NE, emphasizing the importance of regional analyses in tissue amines determination.


Serum dopamine-beta-hydroxylase activity in rat during post-natal development. Rat serum dopamine-beta-hydroxylase (DBH) activity is quite high in the immediate post-natal period reaching peak activity (75 units) at 16 days of age. Activity then decreases rapidly over the following weeks to approach adult levels (10 units) by seven weeks of age. Also, specific activity of DBH in heart increased rapidly during the first 2 1/2 weeks of life attaining adult levels by 18 days of age. In contrast, heart weight and total DBH activity in whole heart increased in a coordinate fashion at a relatively constant rate throughout the first seven weeks of life. Serum levels of non-copper sensitive endogenous inhibitor (s) of DBH increased throughout the first seven weeks of life while no change in copper sensitive inhibition was observed. Also, the rapid phase of decrease in serum DBH activity corresponded to the period of the most rapid increase in body weight.


Insulin coma therapy: decrease of plasma tryptophan in man. A biochemical study was performed in two patients submitted to insulin coma therapy. The injection of insulin resulted in a decrease of free and total tryptophan as well as tyrosine in plasma, while NEFA were not influenced by this treatment. The ratio of tryptophan to tyrosine was enhanced. The administration of glucose after insulin provoked an increase of free and total tryptophan. The results support the hypothesis that in man insulin may favor the uptake of tryptophan by the brain, and enhance the synthesis of cerebral serotonin.


The nerve lesion in the carpal tunnel syndrome. The relative roles of pressure deformation and ischaemia in the production of compression nerve lesions remain a controversial issue. This paper concerns the genesis of the structural changes which follow compression of the median nerve in the carpal tunnel. The initial lesion is an intrafunicular anoxia caused by obstruction to the venous return from the funiculi as the result of increased pressure in the tunnel. This leads to intrafunicular oedema and an increase in intrafunicular pressure which imperil and finally destroy nerve fibres by impairing their blood supply and by compression. The final outcome is the fibrous tissue replacement of the contents of the funiculi.


Treatment of benign intracranial hypertension by dehydrating agents with particular reference to the measurement of the blind spot area as a means of recording improvement. A series of 30 patients (28 females : 2 males) presenting with benign intracranial hypertension is reported. It is shown that the papilloedema may be resolved in as little as six weeks by the use of dehydration therapy. Evidence is presented that this method can restore to normal a visual acuity which is as low as 6/24 or even 6/36. It is concluded that surgery is never required in the management of this condition. It is strongly recommended that serial blind-spot measurements should be used routinely to assess the effectiveness of therapy. Fluorescein angiography has a place in diagnosis among a small proportion of these patients.


Assessment of the severity of head injury. Ranking of head injuries by severity is an essential part of clinical management, of prognosis, of treatment trials, and of legal assessment for compensation. Various methods of assessing severity are reviewed. No one scale is appropriate for all types of injury, or in all circumstances. A check list is provided which should enable every injury to be assessed; its use would facilitate comparison between individual cases of head injury, and between reports from different studies.


Incidence of postoperative epilepsy after a transtentorial approach to acoustic nerve tumours. Sixty-nine patients who had neurosurgical treatment for acoustic neuroma by one of two different techniques were studied with a view to determining the incidence of postoperative epilepsy. Fourty-five patients who had larger tumours underwent a combined translabyrinthine and transtentorial neurosurgical approach. For the others with smaller neuromas a translabyrinthine method was used. Only the combined approach was associated with postoperative epilepsy, and it occurred in 22% of the patients. Epilepsy was associated with temporal love trauma during surgery.


Cutaneous silent period in masseter muscles: a clinical and electrodiagnostic evaluation. In 35 normal subjects electromyographic silent periods were constantly evoked bilaterally in the masseter muscles during maximal contraction after unilateral electrical stimulation over the infraorbital or mental nerve. Findings in this study and data obtained in 30 patients suffering from trigeminal (26) and facial (four) nerve lesions suggest that the silent period evoked according to our methods is cutaneous in origin. The trigeminal sensory root forms the afferent limb of the silent period reflex. Its central pathway is thought to pass both crossed and uncrossed through the pons. Determination of the cutaneous silent period might be of value for the demonstration of trigeminal nerve lesions and to supplement results concerning other brain-stem reflexes.


Electromyography in nutritional osteomalacic myopathy. Electromyographic studies in 15 women with nutritional osteomalacia and proximal muscle weakness showed brief duration motor unit action potentials of normal amplitude and increased proportion of polyphasic motor unit potentials in the majority of them. By employing quantitative methods of electromyography, more positive results were obtained, thus reducing the sampling data. The histology showed non-specific muscle fibre atrophy without degenerative changes and the clinical and electromyographic examinations together showed clear evidence of a myopathy, suggesting a reversible transient block of the muscle fibres. Contrary to a recent suggestion, the nature of muscular change in osteomalacia remains the same regardless of its cause being nutritional or otherwise.


Nerve fibre velocity and refractory period distributions in nerve trunks. With the use of a double stimulus technique, nerve fibre velocity range measurements were performed over a single conduction distance in 13 normal subjects and over two conduction distances in another 12 normal subjects. The velocity ranges were found to be dependent upon the conduction distance, owing to unknown refractory period delays. Refractory period values were calculated for the 12 subjects and also direct refractory period distribution measurements were made on 15 normal subjects using a twin stimulus and automatic subtraction technique. Corrections to the velocity range measurements were made upon differing assumptions as to the correlation between refractory period and fibre conduction velocity. It was concluded that a single median value refractory period obtained from the distribution was the best correction to use, based upon the hypothesis that for group A fibres the random scatter of refractory period values is far greater than any variation due to a correlation between refractory period and fibre conduction velocity. It was found important to recognize that calculated values of velocity range are a function not only of the spread of fibre conduction velocities but also of refractory periods.


Methylmercury poisoning, Clinical follow-up and sensory nerve conduction studies. Methylmercury poisoning occurred in four cases after passage of methylmercury through the food chain. The neurological damage in all four cases was severe. The damage was greater at younger ages with maximum involvement in the case of transplacental poisoning. Significant recovery occurred in two cases, but on six-year follow-up two cases remained severely impaired. Clinical and electrophysiological evidence suggests that damage to peripheral sensory nerves may not be the cause of the late sensory symptomatology.


Gelastic, quiritarian, and cursive epilepsy. A clinicopathological appraisal. A patient is reported with episodes of epileptic laughter, crying, and running occurring alone or in combination. He was found to have discrete, well-circumscribed tumour of the left temporal lobe. The neurology of these epileptic events is discussed in relation to the pathological lesion.


Dacrystic epilepsy.

Dacrystic epilepsy. We observed a 69 year old patient who had spontaneous paroxysmal attacks of weeping with lacrimation, contorted facies, and (usually) head-turning to the right. These episodes were followed by confusion and amnesia. During a pentylenetetrazol-evoked attack the EEG showed a right temporal delta rhythm. Atrophy, particularly of the right temporal regions, was noted on pneumoencephalography. We propose the term "dacrystic epilepsy" for this rare type of seizure disorder.


A large cirsoid aneurysm of the scalp associated with epilepsy. A large cirsoid aneurysm of the scalp that was present since birth in a 1 1/2 year old baby is reported. For six months the patient had been suffering from generalized seizures and mental retardation. After excision of the aneurysm, the patient became seizure free.


Carotid-ophthalmic aneurysms.

Carotid-ophthalmic aneurysms. Thirty-two cases of carotid-ophthalmic aneurysms are reviewed. As with intracranial aneurysms in other positions they present mainly with subarachnoid haemorrhage but, in spite of their close proximity to the optic nerve, visual involvement is infrequent. They are more common in women, more frequent on the left side, and more prone to multiplicity. In cases of multiple aneurysms a carotid-ophthalmic aneurysm is usually an incidental finding. Detailed angiographic studies employing various projections are required before treatment can be planned. Yet angiography does not always disclose some of the technical difficulties that may be encountered during surgery. Different methods of treating these aneurysms are discussed and suggestions for safe direct surgery made.


Transient third nerve palsy after electrometallicthrombosis of carotid cavernous fistulae. Three patients had oculomotor nerve palsy as a complication of the treatment of carotid cavernous fistulae by electrometallicthrombosis of the cavernous sinus. In two, third nerve function returned without misdirection in two months or less. One was left with a partial third nerve palsy, also without misdirection.


A possible means of monitoring the progress of demyelination in multiple sclerosis: effect of body temperature on visual perception of double light flashes. The ability to discriminate closely separated pairs of light flashes as being double is impaired in multiple sclerosis. The effects of altering body temperature on double flash resolution and on visual acuity were studied in four multiple sclerosis patients and in control subjects. At demyelinated sites heating impaired and cooling improved double flash resolution. Visual acuity behaved similarly. The double flash test was very sensitive, changing up to 75 ms in response to simple heating and cooling procedures that produced small variations in acuity. Apart from its diagnostic value, the double flash test furnishes a simple in vivo model to study the effect of temperature change (and potential symptomatic therapy) on conduction in partially demyelinated axons in the visual system.


Effect of apomorphine on growth hormone and prolactin secretion in schizophrenic patients, with or without oral dyskinesia, withdrawn from chronic neuroleptic therapy. Serum growth hormone (GH) and prolactin (PRL) concentrations were measured after administration of the dopamine receptor agonist, apomorphine HC1 (0.75 mg subcutaneously), to 17 chronic schizophrenic patients, four of whom had an oral dyskinesia, who were withdrawn from chronic neuroleptic therapy for periods of two to 15 weeks, and in 21 control subjects (normal volunteers or physically healthy alcoholics not exposed to neuroleptics). Six of the schizophrenic patients, but none of the controls, had raised baseline levels of GH (greater than 6 ng/ml). After apomorphine all controls showed an increase in serum GH with a peak concentration of 9 ng/ml or more, whereas eight subjects withdrawn from neuroleptics showed an inadequate response (peak less than 6 ng/ml) and in two others an inadequate response was obtained on one of two trials. The peak GH concentration was significantly less after apomorphine in patients withdrawn from neuroleptics (11.90 +/- 3.19 ng/ml) compared with controls (20.80 +/- 2.11 ng/ml) (P less than 0.05). Among patients withdrawn from neuroleptics, those with an oral dyskinesia had significantly lower peak GH concentration 2.46 +/- 0.93 ng/ml) after apomorphine compared with those without (14.85 +/- 3.83 ng/ml) (P less than 0.05). There were no differences in serum PRL concentrations, before or after apomorphine administration, between patients withdrawn from neuroleptics and controls. In uncontrolled observations none of the four patients with an oral dyskinesia showed any worsening of the movement disorder after apomorphine. These data provide no evidence for supersensitivity of dopamine receptors in chronic schizophrenic patients withdrawn from chronic neuroleptic therapy.


Effects of a carbonic anhydrase inhibitor on cerebral blood flow in geriatric patients. A carbonic anhydrase inhibitor (UK-12,130) was shown to increase cerebral blood flow in mildly demented geriatric patients. Oral administration caused a significant increase in blood flow at two different dose levels; this persisted for at least six weeks, which was the duration of the longest study. There was no consistent improvement in mentation during treatment. Blood blow was measured by the washout of 133Xe after inhalation of this inert gas.


Pure motor hemiplegia, medullary pyramid lesion, and olivary hypertrophy. The case is presented of a 60 years old man who developed sudden right hemiplegia without other accompanying neurological signs and later a spastic hemiparesis. Neuropathological studies indicated an ischaemic lesion of the left medullary pyramid which was accompanied by hypertrophy of the left inferior olivary nucleus. An additional lesion, demyelination of the right gracile tract, is poorly explained. This case represents the second reported instance of pure motor hemiplegia due to a circumscribed lesion in the medullary pyramid and possibly an unique instance of olivary hypertrophy without obvious damage to the central tegmental tract, ipsilateral superior cerebellar peduncle, or contralateral dentate nucleus. The olivary hypertrophy is thought to have arisen from local damage to the termination of the central tegmental fibres at the left inferior olivary nucleus. The question of the development of spasticity in a pure pyramidal tract lesion is discussed.


Motor and sensory conduction in the musculocutaneous nerve. Motor and sensory conduction velocity in the musculocutaneous nerve were determined in 51 normal subjects. The maximal velocity from the anterior cervical triangle to the axilla was the same in motor and sensory fibres. The conduction velocity decreased 2m/s per 10 years increase of age. It was 70 m/s at 15-24 years and 58 m/s at 65-74 years. The velocity of the slowest components in sensory fibres was 17 m/s. Three selected case reports illustrate the diagnostic value of the method.


Axonal excitability and motor propagation velocity of peripheral nerves in patients with acute vascular lesions of the brain. From measurements of maximum and minimum motor nerve propagation velocity and neuronal excitability we conclude that there is a functional loss of motor units and distal nerve "dying back" in persons affected with unilateral acute cerebral vascular lesions. The study also suggests that transynaptic degeneration affects the lower motor neurone function on both sides.


Computerized tomography in the diagnosis of cerebral atrophy. Computerized tomograms were studied of 67 adults whose lumbar pneumoencephalograms were normal or showed ventricular dilatation with or without widening of the sulci. The maximum ventricular area, measured from 80 x 80 matrix printouts, correlates well with measures of ventricular size on the pneumoencephalogram. An area of 10 cm2 is suggested as the upper limit of normal. The correlation between measures of sulcal width on computerized tomography and pneumoencephalography is less precise, but normal sulci and gross degrees of cortical atrophy can be identified.


Freeze-fracture aspects of the perineurium of spinal ganglia. The internal portion of the capsule of the spinal ganglia of rabbit is composed of continuous superimposed layers of flattended cells (perineurium). In replicas, extensive meshworks of strands, presumably forming zonulae occludentes, are found between the perineurial cells of the same layer. Adjacent layers are joint by maculae occludentes located on the lateral processes of the perineurial cells. Occasionally small gap junctions lie within the meshes of the zonulae occludentes.


The fine structure of synapses in relation to the large spherical neurons in the anterior ventral cochlear of the cat. The fine structure of synapses in relation to the large spherical neurons, the principal neurons in the anterior ventral cochlear nucleus (AVCN) of the cat, was studied. Axo-somatic synapses were classified into three types based on their size and shape and the distribution of synaptic vesicles. Axo-dendritic synapses were also classified into three types with respect to synaptic contact, cytoplasmic densities associated with the pre- and postsynaptic membranes and the shape of the synaptic vesicles. Mossy fibre-like endings and preterminal axons containing dense-core vesicles were observed in this study. Serial or triadic synapses were also found in cat AVCN. We occasionally found a nematosome in the cytoplasm of the principal neuron.


Sensory terminals on extrafusal muscle fibres in myotendinous regions of developing rat muscles. Axon terminals were observed to form neuromuscular contacts with extrafusal muscle fibres in myotendinous regions of developing rat muscles up to 5 days after birth. These neuromuscular contacts are found in fascicles of muscle fibres connected with differentiating Golgi tendon organs. Axon terminals establishing these contacts are obviously sensory, since they do not degenerate after de-efferentation performed in neonatal rats. The terminals contain mainly clear and dense core vesicles and form neuromuscular connections resembling developing motor endplates, with a cleft about 60 nm wide and basal lamina interposed between the axolemma and the sarcolemma. Each terminal, however, also forms a close contact in a restricted region where the basal lamina is missing; there the cleft is reduced to 20 nm and the axolemmal and sarcolemmal membranes are linked by desmosome-like attachment plaques. After the fifth postnatal day, axon terminals become detached from muscle fibres and are only found among collagen bundles of the tendon organ. The functional significance of these temporary neuromuscular contacts is not clear.


Striated muscle in the pineal gland of swine. Striated muscle fibers (or cells) were observed in three of the six swine pineal glands. The muscle fibers occurred in clusters of several fibers about the parenchymal blood vessels. They were in general poorly developed, lacked regular cross striations and were not readily recognized histologically. The muscle fibers were, however, easily identified on electron microscopy because of the myofilaments they contain. In most of the muscle fibers, the myofilaments were arranged in ill-defined, disorderly bundles and rarely formed well-defined myofibrils and sarcomeres. The sarcotubular system was also poorly developed and triads were sparse and randomly scattered. Leptomeres were observed in several muscle fibers. The source of the muscle fibers in the pineal glands is not well understood and, whatever the source may be, the muscle fibers seem to remain poorly developed in the pineal glands.


Cytological organization of the dorsal lateral geniculate nuclei in mutant anophthalmic and postnatally enucleated mice. The dorsal lateral geniculate nuclei (dLGN) of anophthalmic and early postnatally enucleated mice were studied to determine the role retinal fibres play in the differentiation of postsynaptic target structures. Cell counts indicate that retinal fibres are necessary for the development and maintenance of the normal number of dLGN neurons and glia. This retinal fibre dependence is greater for animals enucleated on postnatal day 3 than for animals with a congenital absence of optic axons. Golgi analysis reveals, however, that the lack of retinal fibres does not preclude the development of the thalamo-cortical and intrinsic types of dLGN neuron. Ultrastructural analysis reveals that in anophthalmic and early postnatally enucleated mice, dLGN synaptic sites normally occupied by optic axon terminals become innervated by large terminals containing round synaptic vesicles and mitochondria with an electron dense matrix. Significantly, the formation of these replacement terminals does not seem to depend upon either the previous existence of retinal fibres or the postnatal stage at which retinal fibres are removed. The possibility that some of these large replacement terminals originate from cortical or recurrent collateral axons is considered.


Effects of an ionophore, X-537A, on mouse CNS cultures: a light and electron microscope study. The effects of the ionophore X-537A on organotypic CNS tissue culture were investigated with bright field and electron microscopy. In addition to condensation of mitochondria this agent was found to induce a relatively selective vacuolation of the Golgi apparatus of neurons and glial cells. At the dosages used (50 mug/ml for 2-3 hours and 100 mug/ml for 1 hour) these changes were irreversible. Additional experiments suggested that the cellular effects of X-537A were primarily due to its ability to translocate Na+ across cellular membranes.


A special type of small granule-containing cell in the abdominal para aortic region of the frog. Light and electron microscopic studies have been made of a special type of small granule-containing cell (termed Type IV cell) in the frog abdominal para aortic region. These cells contain numerous dense granular vesicles (100--150 nm in diameter) and are considerably smaller (10--20 mu) than neighbouring nerve cells, although they have many features in common with them. They do not resemble chromaffin cells as do Types I, II and III cells. The cell bodies are completely ensheathed by satellite cells and are isolated from neighbouring cells of the same type. Type IV cells have long processes which usually become incorporated in bundles containing 2--20 processes, including some cholinergic nerve fibres, and are loosely enveloped by perineurium. The termination of the processes of Type IV cells do not appear to form efferent synapses on nerve cells at least within the para aortic region or in paravertebral sympathetic ganglia. A close topographical relationship is not found between these processes and blood vessels. It is suggested that the small Type IV granule-containing cells in the frog abdominal para aortic region are not interneurons or neurosecretory cells, but are a special type of sympathetic nerve cell.


Intercellular junctions in the reticular lamina of the organ of Corti. Junctions between the cells in the reticular lamina of the organ of Corti were examined in thin sections and after freeze-fracturing to find a structural basis for the large ionic differences between the endolymph and perilymph. The apices of the cells in the reticular lamina are joined by a band of tight junctions spaced at 140 A intervals. Beneath this apical band the organization of the tight junctions depends on whether they join a supporting cell and a hair cell, or two supporting cells. At hair cell junctions with supporting cells, there is an extensive labyrinth of tight junctions enclosing lengthy, tortuous passages whose walls are composed of either multiple parallel or single junctions. At appositions between two supportinc cells, maculae or fasciae occludentes lie immediately beneath the apical bands of closely spaced tight junctions, near the top of the zonulae adherentia which are characteristic of appositions between supporting cells. The complexes of tight junctions, or zonulae occludentes, between extralaminar supporting cells differ from those in the reticular lamina. The extralaminar cells are joined by a band of four to seven branching, anastomotic tight junctions. Thus, these junctions are like zonulae occludentes in other tissues. The novel organizations of the tight junctions in the reticular lamina, different from those between the extralaminar supporting cells, suggests a special role for these junctions in the reticular lamina. Two sizes of gap junctions link, and presumably couple, supporting cells in the reticular lamina.


Sarcoma arising in oligodendroglioma of the brain. A case is reported of a tumor composed of both oligodendrogliomatous and sarcomatous elements. The interpretation is offered that the sarcoma arose secondarily by neoplastic transformation of the hyperplastic blood vessels formed in response to the presence of the oligodendroglioma. This tumor may be considered analogous to the astrocytoma-sarcoma, which is much more common, and to the metastatic carcinoma with secondary sarcoma, of which one case has been reported.


Excitability changes of terminal arborizations of single Ia and Ib afferent fibers produced by muscle and cutaneous conditioning volleys. 1. In cats anesthetized with sodium pentobarbital, recordings were made from dorsal root ganglion (DRG) cells having a peripheral process in the gastrocnemius-soleus (GS) nerve. The GS nerve was left in continuity with the muscle to allow identification of group Ia and Ib fibers by responses of the receptors to muscle stretch and contraction. The central processes of the DRG cells were activated antidromically by stimulation within the spinal cord so that changes in the excitability of the fibers could be examined following conditioning volleys in muscle and cutaneous nerves. 2. Recordings were made from 44 DRG cells. Of these, 15 were group Ia and 9 group Ib afferents of the GS nerve. 3. Of 15 Ia fibers, 12 were activated antidromically by stimulation in the motor nucleus, but no Ib fibers were discharged by such stimulation. Ib fibers could be antidromically activated by stimulation in the intermediate nucleus. 4. The central processes of the Ia DRG cells had slower conduction velocities than did the peripheral processes. 5. The thresholds to electrical stimulation of the peripheral processes of Ia and Ib fibers of the GS nerve showed considerable overlap. 6. All of the Ia DRG cells tested showed an increased excitability following conditioning volleys in the biceps-semitendinosus (BST) nerve. The increase in excitability was produced by the largest fibers of the BST nerve. 7. Stimulation of the sural (SU) or superficial peroneal (SP) cutaneous nerves also increased the excitability of some Ia fibers. However, other Ia fibers were unaffected, and in two cases the excitability was reduced. 8. The excitability of group Ib fibers was increased by conditioning volleys in the BST, SU, or SP nerves. 9. It is concluded that cutaneous volleys produce a mixture of primary afferent depolarization and primary afferent hyperpolarization in Ia fibers of anesthetized cats. Such converse actions probably cancel in excitability tests using population responses. 10. The excitability of single Ia fibers is not stationary in excitability presumably reflect slow alterations within the central nervous system, perhaps related to spontaneous alterations in the level of tonically maintained primary afferent depolarization.


Current excitation threshold in sensory neurons of leech central nervous system. 1. Sensory cells in segmental ganglia of the leech (Hirudo medicinalis L.), N (noxious), P (pressure), and T (touch) cells, were stimulated by linearly rising currents. The electrical response to intracellular stimulation with prolonged square-wave currents, the shape of the action potential, and the degree of repetitive activity were also examined. 2. The thresholds for first production of an action potential by linearly rising currents (expressed as multiples of rheobase, I/IO), plotted as a function of the action-potential latency, provide a measure of accomodation. These T-L curves show that the P and T cells accommodate more rapidly than the N cells. 3. An index of accommodation, the accommodation coefficient (I/Io)s/2, was defined as the current required to elicit a first action potential 0.5 s after the beginning of a linearly rising stimulus current. These accommodation coefficients also reflect the property that P and T cells accommodate more rapidly, on the average, than N cells. 4. Threshold depolarization is higher with linearly rising currents than with square-wave currents. 5. Comparison of the accommodation rates of these sensory somata with the published data for other somata and axons, on the basis of accommodation coefficient, minimal current gradient, and/or threshold-latency curve, shows that a) N cells, at the slow end of the leech-soma accommodation range, accommodate at about the same rate as most vertebrate neurons; and b) some vertebrate neurons have accomodation rates as high as or higher than those of the T and P cells. The accommodation rates of most vertebrate neurons are related in a characteristic way to undershoot shape, repetitive-firing properties, and adaptation. Comparable relationships are found in the leech if the N and T cells alone are considered, but the P cells (with extremely rapid accomodation) depart notably from this pattern--they adapt slowly, fire repetitively in response to a maintained stimulus, and have an undershoot of intermediate amplitude and duration.


Sensory neurons in leech central nervous system: changes in potassium conductance an excitation threshold. 1. The sensory neurons in the leech central nervous system differ in their accommodation to linearly rising currents. Advantage was taken of these differences to study the ionic mechanism of accommodation in single pairs of N (noxious), P (pressure), and T (touch) cells. 2. Nonlinearities in membrane-potential changes and current-voltage relationships with square-wave and ramp currents are more pronounced in P and T cells than in N cells. The accommodation coefficients increase in conditions that reflect this delayed rectification. When rectification is absent, the accommodation coefficients depart from unity only slightly or not at all. 3. Accommodation coefficients remain unchanged when half of the chloride in the bathing medium is replaced by sulfate. Accommodation coefficients become greater when the extracellular potassium concentration is reduced from 4 to 0 mM, and decrease when the concentration is raised to 8 mM. The membrane potential changes by only a few millivolts. 4. As extracellular potassium concentration is increased, the action potential is lengthened and the maximal rate of fall of the action potential is reduced. With concentrations greater than 4 mM these relationships are linear, but depart from linearity at lower concentrations. The amplitude of the undershoot decreases linearly as the extracellular potassium concentration increases from 4 to 16 mM, and increases non-linearly at concentrations below 4 mM. 5. The rapid accommodation of leech neurons is based primarily on an increased potassium conductance. The possibility is considered that concentration changes like those produced experimentally may occur naturally, affecting integrative processes in the central nervous system.


Properties of relay cells in cat's lateral geniculate nucleus: a comparison of W-cells with X- and Y-cells. 1. Observations are presented on the physiological properties of W-, X-, and Y-type relay cells in the cat's lateral geniculate nucleus (LGN). Emphasis is placed on the most recently recognized type, W-cells; data are presented on X- and Y-cells by way of comparison. 2. Seventy-seven W-cells were recognized on 70 microelectrode penetrations through the LGN. They resembled W-type retinal ganglion cells in their responses to visual stimuli. Tonic (on-center and off-center) W-cells, phasic (on-, off- and on-off center) W-cells, suppressed-by-contrast, and color-coded cells were recognized. 3. W-type relay cells also resembled retinal W-cells in their maintained activity and receptive field-center diameters. 4. W-type relay cells comprised 11.5% X-cells 48.4%, and Y-cells 22.3% of all LGN cells encountered on a reference sample of 62 electrode tracks. W-cells were found in laminae C, C1, and C2, comprising 36.5% of the sample in these laminae, but were not encountered in laminae A or A1. X- and Y-cells were found in laminae A, A1, and C. Within lamina C there was a tendency for X- and Y-cells to be located dorsal to W-cells. There was thus a substantial dorsoventral segregation of W-cells from X- and Y-cells. W-cells being found in the ventral parvocellular component of the dorsal LGN. 5. Cells considered to be W-type relay cells were shown to respond to electrical stimulation of the optic nerve and chiasm at latencies which were longer than those of X- and Y-cells, and were consistent with their receiving monosynaptic input from retinal W-cells. Geniculate W-cells of all subtypes were activated antidromically from the visual cortex. Their antidromic latencies were, on the average, longer than for Y- or X-cells, indicating that W-type relay cells had slower axons as well as slower retinal afferents, than X- or Y-cells. 6. The visual cortex thus appears to receive input from all three major types of retinal ganlion cells (W-, X-, and Y-cells) relayed separately, in parallel, by different groups of relay cells.


Effect of stimulation with light on synthesis and release of acetylcholine by an isolated mammalian retina. 1. Acetylcholine synthesis and release were studied in rabbit retinas isolated from the eye and incubated under conditions in which their electrophysiological function is maintained. ACh synthesized from exogenous [14C] choline appeared in the retina at an initial rate of 16 nmol/g wet wt-h. Incorporation of labeled choline into ACh was accelerated by stimulation of the retina with light. 2. Retinas incubated for 40 min in the presence of labeled choline and then superfused with a medium containing an anticholinesterase released radioactive ACh into the perfusate. The rate of release increased approximately fourfold during stimulation with light. 3. When retinas were incubated with labeled choline and then superfused with medium containing no pharmacological agents, stimulation with light caused an increased release of choline into the perfusate. The recovery of labeled choline following stimulation was enhanced by hemicholinium 3. 4. Neither the light-induced release of ACh (in perfusate containing anticholinesterase) nor the light-induced release of choline (in perfusate containing no anticholinesterase) occurred if the perfusate contained 20 mM Mg2+ and 0.2 mM Ca2+. 5. Synthesis of ACh by the retina at a high rate, acceleration of choline incorporation by stimulation, and Ca2+-dependent release of ACh by stimulation are each presumptive evidence that the retina contains a cholinergic synapse. If this presumption is correct, one such synapse may be of an amacrine or bipolar cell since these cells can depolarize during illumination, whereas the predominant response of receptor and horizontal cells is hyperpolarization.


Responses to acetylcholine of ganglion cells in an isolated mammalian retina. 1. Rabbit retinas were isolated and superfused with a physiological medium. Ganglion cell activity was recorded during stimulation with focused light, and receptive fields were mapped. Receptive fields were identical to those found in vivo and did not change during a 6-h incubation. After the receptive field of a ganglion cell had been identified, acetylcholine or related agents were introduced singly or in combination into the medium, and their effect on the cell's spontaneous and light-evoked activity was observed. 2. Ganglion cells with on-center or directionally selective receptive fields were excited when ACh was added to the medium. The response to exogenous ACh was prevented by cholinergic antagonists. 3. These cells' spontaneous activity and response to light were enhanced by anticholinesterase and depressed by cholinergic antagonists. Antagonists varied in their ability to block the light-evoked response, with dihydro-beta-erythroidine the most effective. 4. Thresholds for ACh or the related agents were low, ranging from 1 to 40 muM; their effects were rapidly and completely reversed when the retina was returned to control medium. 5. In retinas incubated in medium containing 20 mM Mg2+ and 0.2 mM Ca2+, ganglion cells lost completely both their spontaneous and light-evoked activity, but retained their ability to generate action potentials in response to elevated K+. Ganglion cell activity rapidly returned to normal when the retina was returned to medium containing normal electrolytes. On-center and directionally selective cells were excited by ACh in retinas where synaptic transmission had been inhibited by 20 mM Mg2+ and 0.2 mM Ca2+. 6. The responses of on-center and directionally selective cells to ACh, to anticholinesterase, and to cholinergic antagonists in control medium indicate that the retina contains one or more synapses using ACh as a neurotransmitter. The response to ACh in retinas exposed to 20 mM Mg2+ and 0.2 mM Ca2+ suggests that at least one such synapse in on the ganglion cell itself. 7. Off-center cells were inhomogenous in their response to ACh. Although some responded just as the other classes of cell, the majority responded quite weakly and a subgroup was encountered which was entirely unaffected by even 1 mM ACh, by levels of physostigmine which inactivate virtually all retinal acetyl-cholinesterase, or by high concentrations of cholinergic antagonists. Only 2 of 20 off-cells tested in the presence of 20 mM Mg2+ and 0.2 mM Ca2+ were excited by ACh. Apparently ACh is not a primary transmitter for most off-cells.


Sustained, synchronous oscillations in discharge of sustaining fibers of crayfish optic nerve. 1. The regularity of the sustaining fiber (SF) steady-state discharge increases with the intensity of a uniform field of illumination. 2. In a high levels of illumination SFs exhibit a highly periodic or rhythmically bursting steady-state discharge. 3. The period of the burst cycle is independent of the light intensity and the mean firing rate. 4. Multimodal interspike-interval histograms in which successive modes decline exponentially suggest that the discharge arises from a regular input. 5. In conditions of uniform illumination, the regular input must be common to all or several SFs since the period of the burst cycle of simultaneously monitored SFs are the same and cross-correlations indicate that the SFs burst in approximate synchrony. 6. It is proposed that the common, regular input is a network of presynaptic elements exhibiting recurrent lateral inhibition. Evidence supporting this hypothesis is that following a brief light pulse to the inhibitory surround, SFs exhibit cycles of silence and bursting, phase-locked to the stimulus but with a period equal to the steady-state burst-cycle period. 7. Furthermore, lateral inhibitory influences are common to several or all SFs as indicated by the close similarity in response time course of two SFs subjected to a common inhibitory stimulus. 8. The response of the lateral pathways to sinusoidally modulated illumination is highly selective to frequencies near the burst-repetition rate. The excitatory pathways exhibit frequency modulation or entrainment over a wide range of input frequencies. 9. The intersustaining burst cycle phase is under partial visual stimulus control (position and intensity) and the possibility of phase coding in the SF ensemble is discussed.


Photoreceptor thresholds and visual pigment levels in normal and vitamin A-deprived Xenopus tadpoles. 1. Measurements of the aspartate-isolated PIII component of the electroretinogram (ERG) were used to estimate photoreceptor threshold in dark-adapted tadpoles of the clawed toad, Xenopus laevis raised on a normal diet. Spectral sensitivity functions established that the rod mechanism governed absolute dark thresholds from stage 40 to the end of premetamorphic development. 2. Parallel measures of rod outer-segment dimensions and visual pigment levels demonstrated a) that visual pigment concentration remained constant at all tadpole stages, and b) that the fall in threshold over the course of premetamorphic development depended exclusively on the increased probability of quantal absorption that accompanied the growth of the rod outer segments. 3. When tadpoles were obtained from vitamin A-deficient females and raised subsequently on a vitamin A-free diet, the first appearance of the ERG was delayed and its absolute threshold raised, with respect to controls. 4. Histological examination of vitamin A-deprived retinas indicated that rod outer segments retained their structural integrity in spite of up to a 75% loss of visual pigment. 5. The threshold rise which accompanied a fall in visual pigment levels, whether effected by dietary deficiency or by bleaching, was greater than could be attributed solely to a reduction in the probability of quantal absorption.


Radionuclide angiographic diagnosis of bronchopulmonary sequestration. Bronchopulmonary sequestration (BPS), a congenital malformation that usually presents as a chest mass in childhood, may be identified by its characteristic primary derivation of pulmonary blood supply from the systemic circulation. Five children with BPS were evaluated by radionuclide angiography from 1970 to 1974. In each instance the systemic origin of the vascular supply was correctly indicated. In those lesions where the artery originates below the hemidiaphragm, the aberrant source, when identified as such, provides a characteristic radionuclide appearance of BPS. The scimitar syndrome may be indistinguishable from BPS with this technique.


Splenic imaging with 99mTc-labeled erythrocytes: a comparative study of cell-damaging methods. Several methods of damaging red blood cells (RBCs) for splenic imaging were compared to determine the optimum approach. The RBCs from donor animals were labeled with 99mTcO4- and damaged by heat, excess acid citrate dextrose (ACD), excess Sn(II) ion, or the sulfhydryl inhibitors N-ethylmaleimide (NEM) or p-hydroxymercuribenzoate (PMB). The organ distributions of undamaged and damaged RBCs were determined in rats, and splenic imaging studies were performed in rabbits. Splenic deposition and spleen-to-liver ratios with heat- or sulfhydryl-damaged 99mTc-RBCs were significantly greater (p less than 0.001) than the values obtained using ACD or Sn(II) ion. Heat-damaging produces good splenic localization of 99mTc-RBCs but requires rigidly controlled incubation conditions. NEM-damaging provides an excellent and predictable alternative approach.


Calculation of coronary blood flow from myocardial clearance of systemically administered 133Xe. Clearance curves for arterial and coronary-venous blood were determined after systemic left-ventricle or pulmonary-artery infections of 133Xe, paired with selective left-coronary-artery injections of 133Xe in 20 dogs with closed chest. Coronary blood flows calculated from systemic and coronary-artery injections were comparable only when a correction was made for arteriol recirculation of 133Xe following the systemic injection (r = 0.962) for left ventricle and 0.932 for pulmonary artery, paired with coronary artery). Experiments in four other dogs, verified that clearance of 133Xe from the pulmonary circulation was only about 60%. The myocardium/blood 133Xe partition coefficient, determined in vivo in ten dogs, agreed within 10% with that previously determined in vitro.


Comparison of 4- and 24-hr thyroid scans with 123I: concise communication. Thyroid scans were performed at 4 and 24 hr after administration of Na123I solution in 124 examinations. The 4-hr and 24-hr scans were found to be of equal diagnostic value. Thus, in individuals with structural thyroid abnormalities, one can effectively reduce the time required for scan evaluation from the standard 24 hr to 4 hr.


Uptake of 67Ga in the lactating breast and its persistence in milk: case report. The concentration of 67Ga in the milk of a postpartum woman was measured at intervals up to 8 days after the injection of 3 mCi of 67Ga-citrate. The 67Ga concentration was about 0.15 muCi/ml at 3 days after injection and fell to 0.035 muCi/ml by 8 days. Since the biologic clearance of gallium was slow (T1/2 approximately 9 days), the major determinant of the clearance of radioactivity was the physical decay of the gallium. An estimate of the radiation dose to a nursing infant suggests that nursing be interrupted for about 2 weeks after the mother has had a 67Ga study.


An unusual cause of apparent regional hyperperfusion on radionuclide cerebral angiography study: case report. An unusual pattern of radioactivity in the venous phase was noted in the 99mTc-DTPA cerebral angiogram of a patient with persistent headaches. Initially the possibility of a small arteriovenous malformation with large draining veins was considered. However, contrast angiography revealed dilated cerebral veins with significant arteriovenous shunting. The differential diagnosis of regional hyperperfusion on the radioactivity study is discussed.


Radionuclide angiography as an adjunct in diagnosis of ruptured aortic aneurysm: case report. Radionuclide angiography is a rapid, safe, and reliable method of imaging aneurysms of the abdominal aorta in patients who are too ill to undergo contrast angiography or when time is a critical factor.


Evaluation of liposome-entrapped radioactive tracers as scanning agents. Part 1: Organ distribution of liposome (99mTc-DTPA) in mice. We describe the use of liposomes as a delivery system for radiopharmaceutical localization. Liposomes [99mTc-DTPA] were injected intravenously in mice and showed preferential uptake in the liver and spleen. There was a steady decline of activity in all organs, suggestive of destruction of liposomes with subsequent release of 99mTc-DTPA into the circulation. Alteration of uptake from liver to spleen, lung, and bone marrow was achieved by prior loading of the circulation with nonradioactive liposomes. The same effect was produced in dogs and demonstrated with scintigraphy. We also showed scintigraphically in dogs how 99mTc-DTPA, when administered entrapped in liposomes, follows the pattern of distribution of liposomes. Liposomes seem to be suitable carriers for radiopharmaceuticals. Further studies should show the possibility of directing liposomes to specific targets.


Vesicle interactions with antibody and peptide hormone: role of vesicle composition. Artificial lipid vesicles (artificial membranes) were shown to bind human 125I-antithyroglobulin (anti-Tg) and human 125I-thyrotropin. Vesicles made with gangliosides bound more antibody and hormone than vesicles lacking them. These gangliosides contained a variety of carbohydrates including glucose, galactose, N-acetyl-galactosamine, and sialic acid. The in vivo stability of antibody-vesicle complexes was a function of vesicle composition: vesicles were most stable when formed from phosphatidylcholine, cholesterol, and gangliosides. Anti-Tg-vesicle complexes bind to thyroglobulin, indicating that at least some of the antibody associated with the vesicle still retains ability to bind to its specific antigen. The addition of a specific antibody or hormone to artificial lipid vesicles may serve as a mechanism to confer specificity to the vesicle in vivo.


Experimental basis of myocardial imaging with 123I-labeled hexadecenoic acid. Progress in myocardial perfusion imaging has been slowed by the lack or radiopharmaceuticals with suitable physical and biologic characteristics. Hexadecenoic acid, terminally labeled with 123I, partially overcomes these limitations by providing a compound that concentrates in the myocardium in proportion to relative regional blood flow and carries a gamma-emitter with desirable detection and imaging qualities. After intravenous injection in experimental animals, the clearance half-times of hexadecenoic acid for blood and myocardium are 1.7 and 20 min, respectively. These values compare favorably with 18-carbon fatty-acid analogs labeled with 11C. In acute and chronic infarction, similar distribution patterns are found for hexadecenoic acid and 43K, which indicates that hexadecenoic acid is a suitable substitute for the potassium analogs now in use for myocardial imaging. Because of the high count rates obtainable with 123I-hexadecenoic acid, good-guality images can be acquired in as little as 2-3 min per view. Iodine-123-hexadecenoic acid is potentially a useful radiopharmaceutical for clinical application.


Kit method of preparation of 4-lodoantipyrine (I-123) from Na123I: concise communication. 4-Iodoantipyrine (4-IAP), containing 123I, has been suggested as a radio-pharmaceutical for direct imaging of regional cerebral perfusion. In routine clinical use, a reliable source of the labeled compound is required. The 4-IAP (I-123) can be prepared by exchange between Na123I and 4-bromoantipyrine (4-BrAP) or 4-IAP with heating in aqueous acidic solution. Using an H3PO4 buffer system at pH 2.5 during labeling, with addition of NaOH for subsequent buffering at pH 7.0, a convenient reliable kit for routine preparation of 4-IAP (I-123) from commercially available Na123I has been developed.


Diagnosis of deep-vein thrombosis with sodium pertechnetate. Sodium pertechnetate was used to image venous thrombosis in the legs of 20 patients with clinical signs of deep-vein thrombosis. The rate-of-uptake ratios and the activity ratios at 3 min and 4 hr after the injection were calculated. Venography was used as a standard. Discrimination, as well as agreement with venography, was highest for the ratios obtained 4 hr after injection, in which case there were ten patients with a pathologic activity ratio and with venographic signs of thrombosis in the leg with increased uptake. There were six with a normal activity ratio and no venographic signs of thrombosis, but one patient had a normal ratio and abnormal venography.


Effect of small amounts of 131I on 99mTc detection by the scintillation camera. A patient who had recently received a therapeutic dose of Na131I showed no 99mTc activity on the scintillation camera when a pertechnetate brain scan was attempted. Subsequent experiments showed that, when even small amounts of 131I are present in the field of view of a scintillation camera equipped with a collimator designed for low-energy photons, counting rates from 99mTc are markedly affected.


Disparate hydration of adipose and lean tissue require a new model for body water distribution in man. The intra and extracellular fluid spaces in adipose tissue were determined by by 3H2O, 82Br-(minus), and 35SO4= uptake, and by appropriate chemical methods, in surgical biopsy material from 16 patients undergoing elective laparatomy. Total water space for adipose tissue was 14 +/- 1.4%: extracellular component was 11 +/- 1.1% in mesenteric and subcutaneous depots. Use of these adipose tissue hydration constants, combined with measurements of total body water (TBW), extracellular water (ECW), total body potassium, and experimentally derived age-specific constants for lean body potassium content, permits development of a four compartment model for body water which considers intra and extracellular components separately for adipose (AT) and adipose-free (AFM) tissue masses. This model has the form (see journal) where x is the total hydration and y the extracellular hydration of the adipose-free mass. The equations can be solved for the ECW and ICW of the adipose-free mass, defined by its potassium content. In four normal subjects, x was measured as 0.80 +/- 0.032, and y as 0.24 +/- 0.017. Thus, the adipose free mass, compared with adipose tissue, has approximately six times the total water and twice the extracellular water content per unit weight.


The assessment of human body composition during weight reduction: evaluation of a new model for clinical studies. Adipose tissue, the logical target component in weight reduction regimens, was measured in five obese subjects during weight reduction, and in four normal weight controls. The two compartment model of Ljunggren, consisting of adipose tissue (AT) and adipose tissue-free mass (AFM), was further developed by finding experimental values for total water, extracellular water (ECW), lipid, and cell solids in 16 biopsied subjects. The AFM was estimated from body potassium content (40K counting) by use of an age/sex specific constant for the K content in the fat free body. Five obese subjects maintained for 46 days on regimens averaging 800 kcal/day had initial AT from 48% to 60% of body weight compared with AT 27% to 46% in four normal controls. Weight reductions averaged 17.4 kg (12% of initial weight), with approximately equal reductions in adipose tissue, adipose-free mass, and water. Initial fluid compartment ratios in the obese were unusually high (ECW:ICW in AFM was 0.74 +/- 0.23 [S.D.] compared with 0.42 +/- 0.05 in normals); these values returned toward normal (to 0.59 +/- 0.06) with weight reduction. The fact that it was possible to disclose a hitherto unappreciated abnormality of hydration in the adipose-free mass of obese subjects and its change toward normal with weight reduction, suggests that the adipose:adipose-free model may have a special utility when body composition measurements are used to monitor the effects of weight reduction regimens on various body constituents.


Importance of sarcosine formation in methionine methyl carbon oxidation in the rat. Experiments in vitro using rat liver slices indicated that the incorporation of the methionine methyl carbon into sarcosine and serine was dependent upon available glycine and most probably involves glycine methyltransferase. Although the sarcosine methyl carbon was rapidly oxidized to CO2, its formation accounted for only a small proportion of the oxidation of the methionine methyl carbon to CO2 under these conditions. In vivo experiments using a sarcosine trapping pool with 0.3% to 3.0% L-[methyl-14C]methionine in the diet indicated that from 5% to 14% of the absorbed methionine methyl carbon was metabolized via sarcosine, and that this accounted for only 10% to 20% of the observed oxidation of the methyl carbon to CO2. The adaptive response of the rat to high levels of dietary methionine, as indicated by greater oxidation of the methyl carbon to CO2, is in part due to increased sarcosine synthesis. The failure of supplemental glycine to stimulate oxidation of the methionine methyl carbon to CO2 in rats receiving 3% methionine plus 10% sarcosine may be due to sufficient glycine being produced from sarcosine metabolism.


Growth depression and tissue reaction to the consumption of excess dietary methionine and S-methyl-L-cysteine. Similar depressions in growth were observed when rats consumed a 10% casein basal diet containing equal quantities of either methionine or S-methyl-L-cysteine. Supplemental glycine or serine partially alleviated the growth depression caused by the high levels of methionine but were ineffective in alleviating the growth depression caused by high levels of S-methylcysteine. Histological examination of five organs of rats fed the basal, high methionine or high S-methylcysteine diet for 6, 13 or 20 days revealed that only the spleens were affected in that there was erythrocyte engorgement and an accumulation of hemosiderin. The intensity of iron staining in spleens decreased from the second to the third week. The similarity in the depression of growth and splenic damage observed in rats consuming high levels of methionine or S-methylcysteine is consistent with an earlier suggestion that metabolism of the methionine or S-methylcysteine is consistent with an earlier suggestion that metabolism of the methyl group is in some way involved in the toxicity of methionine.


Evidence for S-adenosylmethionine independent catabolism of methionine in the rat. Experiments conducted with rats in vivo comparing the metabolism of methionine and S-methyl-L-cysteine and in vitro comparing methionine, S-methyl-L-cysteine and S-adenosyl-L-methionine indicate that a substantial portion of the oxidative metabolism of the methionine methyl group occurs by pathways that are independent of S-adenosylmethionine formation. Inclusion of 1.2% or 2.4% of S-methyl-L-cysteine in a diet containing 3% of L-methionine depressed the conversion of the methionine methyl and carboxyl carbons to CO2 by 39% and 28%, and 52% and 33%, respectively, for the two levels of S-methyl-L-cysteine. Inclusion of 1.65% of methionine in a diet containing 2.4% of S-methyl-L-cysteine did not affect the conversion of the methyl group of S-methylcysteine to CO2, but 3% of methionine depressed the conversion of the S-methylcysteine methyl group to CO2 to 87% of control values. Greater inhibitions were seen when these substrates were compared in a liver homogenate. In a rat liver homogenate system optimized for the conversion of the methyl group of methionine to CO2, the rate of conversion of the methyl group of S-adenosyl-L-methionine to CO2 was less than 1% of that of methionine even when the concentration of S-adenosylmethionine was saturating. Addition of saturating levels of unlabeled S-adenosymethionine to the homogenate system did not effect the rate of conversion of the methionine methyl carbon to CO2. Although S-adenosylmethionine-dependent metabolism of methionine, leading to incorporation of the methyl carbon into sarcosine and serine, could be demonstrated in liver homogenates, essentially all of the CO2 produced from the methionine methyl group was derived by a pathway or pathways independent of S-adenosylmethionine formation. Formaldehyde and formate have been tentatively identified as intermediates in catabolism of the methionine methyl group by this (these) pathway(s).


Vitamin K requirement and the concentration of vitamin K in rat liver. The concentration of vitamin K was determined in the liver of different strains of rats, and in male and female warfarin-resistant rats by feeding 3H-vitamin K in a purified diet. In each case, the level of vitamin K in the liver correlated approximately with the amount of vitamin K fed. The results indicate that differences in the requirement for vitamin K between the sexes and between strains of rats are due principally to different required concentrations of vitamin K in liver and not to differences in absorption or turnover of the vitamin. The results of the determination of vitamin K epoxide levels in male and female warfarin-resistant rats, and other data, suggest that the amount of vitamin K required in liver may be in part due to differences in the activity of the enzyme, vitamin K epoxide reductase.


Intestinal absorption of phosphate: action of protein synthesis inhibitors and glucocorticoids in the rat. The effect of actinomycin D, cycloheximide and glucocorticoids on the intestinal absorption of phosphate was studied. The effective intestinal absorption of 32P and 47Ca was determined simultaneously in intact rats in vivo using a whole body counter. Both, actinomycin D and cycloheximide caused a significant diminution of the intestinal absorption of phosphate whereas calcium absorption was not altered. Experiments with the in situ ligated loop technique were performed to eliminate the possibility that the action of the protein synthesis inhibitors could be due to an altered intestinal motility effect. Phosphate absorption was also significantly diminished under this condition. On the other hand, the administration of glucocorticoids produced a significant inhibition of phosphate and calcium absorption in the rat in vivo. The reported results indicate that proteins and/or enzymes with a rapid turn-over are involved in the mechanism of phosphate intestinal absorption, and confirm previous observations that phosphate and calcium are transported across the intestine by different mechanisms.


Effect of modified and unmodified tapioca starches on 59Fe retention in rats. The effects of a chemically-modified tapioca starch hydroxypropyl distarch phosphate (HDP), and unmodified tapioca starch (UMS) on 59Fe retention by rats were compared. Three experimental variables were evaluated: 1) the type of starch in the diet, 2) cooking of either the starch alone or the entire diet, and 3) the iron status of the rats. There were no significant differences in 59Re retention between iron-adequate rats fed either UMS or HDP. 59Fe retention by iron-deficient rats was not affected by the type of starch in the diet when uncooked starch was used. However, if the starch was cooked, substitution of HDP for UMS resulted in a significant depression in iron retention by iron-deficient rats. Cooking the entire diet produced a similar but less marked effect. The results of these experiments suggest that the inclusion of one particular type of modified tapioca starch in the diet may affect iron utilization.


Effects of zinc and vitamin A deficient diets on the hepatic mobilization and urinary excretion of vitamin A in rats. Weanling rats were fed diets deficient in zinc (ZD), vitamin A (AD), or both (ZAD) for 3 weeks. Each then received 20 mug of 11,12-3H-retinyl acetate. Plasma retinol was monitored for radioactivity for 5 hours and urine for 6 days. Rats were killed and measurements made of plasma and liver vitamin A and plasma zinc. Plasma vitamin A was depressed but growth was not affected in AD rats compared to pair-fed controls. Radioactivity appeared most rapidly in the plasma retinol fractions of the two vitamin A-depleted groups (AD and ZAD) and was excreted most rapidly in the urine of these same groups. Zinc-deficient diets (ZD and ZAD) caused depressed plasma levels of zinc and vitamin A and growth retardation greater than in pair-fed controls. However zinc deficiency had no effect on mobilization of newly-ingested vitamin A or urinary excretion of labeled metabolites. Liver stores of vitamin A were lower for ZD rats than for controls. The data indicate that zinc deficiency is not a limiting factor in hepatic vitamin A release except as it influences growth and body demand for the vitamin. The data also suggest that newly-absorbed vitamin A is mobilized and utilized in preference to that previously stored in the liver.


Effect of dietary lactose at levels comparable to human consumption on cholesterol and bile acid metabolism of conventional and germfree rats. In recent years, the use of milk products and the concomitant intake of lactose have been tentatively linked to the etiology of cardiovascular disease. An effect of lactose on the microbial modification of acid and neutral sterols has been suggested. In the present study lactose intake, ranging up to 30% of total diet increased beta-muricholic (beta-MC) but not cholic acid concentrations in conventional (CV) rat small intestine to the extent that at the 20% and 30% intake level, the intestinal cholic: beta-MC ratio approached that in germ-free (GF) rats. Total intestinal bile acid (BA) content increased by approximately 1/3, but remained at less than half the value found in GF rats. At lactose intake levels within a range corresponding to the consumption of dairy products often recommended for adult man (5% to 10%) only moderate changes in intestinal, and little change in fecal BA were found during and after the 3 months experimental period. Intestinal beta-MC was increased in the presence and in the absence of an intestinal microflora. Experiments with GF rats fed 10% lactose or 10% maltose indicated that this increase is evoked similarly by both carbohydrates. The slight increase in serum cholesterol levels seen with disaccharide feeding, which became evident only in the GF rats, was again not specific for lactose. No influence was found of lactose feeding on liver cholesterol values. Comparison of CV rats fed nonsterile and radiation-sterilized lactose-containing diets suggested that this mode of sterilization has only a minor influence on the resulting data. When GF experiments are to be incorporated, sterilazation of diet by irradiation with 3.5 to 4.0 X 10(6) Rad is preferable to autoclaving. The present data indicate that no major effect specifically related to a normal dietary intake of lactose on cholesterol and BA metabolism of the adult rat could be demonstrated for the duration of these experiments.


Further studies on the role of the adrenal hormones in responses of rats to meal-feeding. The importance of the adrenal hormones in the lipogenic responses to meal-feeding or starvation-refeeding was studied. In experiment 1, intact or adrenalectomized (ADX) rats were either ad libitum-fed or meal-fed a 65% glucose diet for 21 days or until moribund (ADX rats only). Serum glucose and electrolytes (Ca++, Mg++, Na+, K+), hepatic glycogen and glucose-6-phosphate dehydrogenase (G6PD) and malic enzyme (ME) were determined. ADX rats died within 10 days after the initiation of meal-feeding and were hypoglycemic with low liver glycogen levels and low enzyme activities. No differences in serum electrolytes were observed. In the second experiment, ADX and intact rats of varying initial weights were weight paired and meal-fed. When the  ADX rat died, his intact control was killed and both carcasses assayed for fat content. Heavier rats with presumably more carcass fat survived meal-feeding longer than the lighter rats. Rats died when they had lost all but 2 to 3 g carcass lipid. In experiments 3 and 4, ADX and intact rats were subjected to starvation-refeeding. In experiment 4, additional ADX groups were given supplemental doses of cortisol (0.75 mg/kg, subcutaneous, 2 times daily) during either the starvation period, the refeeding period or during both periods. The activities of hepatic G6PD and ME were determined as well as the levels of liver lipid in experiment 4. Intact starved-refed rats had the usual enzyme overshoot, whereas ADX starved-refed rats did not. Cortisol-treated ADX starved-refed rats had as great an enzyme overshoot as the intact rats and as great an increase in liver lipid. These results suggest that ADX rats die when meal-fed the glucose diet, because they are unable to store sufficient metabolic fuel for use during the starvation phase of the meal-feeding cycle. Further, the results show that glucocorticoids are required for the induction of de novo enzyme synthesis.


Superoxide dismutase activity in polymorphonuclear leukocytes and alveolar macrophages of protein malnourished rats and guinea pigs. Chronic protein insufficiency in utero was achieved by feeding to rat dams an 8% protein diet beginning before breeding and continuing until weaning. Thereafter, the in utero malnourished pups were fed the 8% protein diet. Superoxide dismutase (SOD), an enzyme which protects against superoxide radical, was quantitated in pellet and supernatant of polymorphonuclear leukocytes (PMN) and alveolar macrophages (AM). The AM of rats malnourished in utero contained 1.7 times as much protein and 3 times as much total SOD activity as the AM of control rats. In PMN of these rats, the amount of protein and SOD activity was the same. Significantly larger number of Streptococcus mutans were located from the dental plaque of the in utero malnourished rats. AM isolated from female guinea pigs fed a 9% protein diet from weaning at 11 days of age contained 1.5 times as much protein and twice as much SOD activity as AM from normal guinea pigs. However their PMN contained smaller amounts of total protein and SOD activity. The malnourished guinea pigs had a mammary gland infection and a prolonged conjunctival infection following inoculation with Guinea Pig Inclusion Conjunctivitis indicating that these animals were more susceptible to these infections. The increase in total SOD activity and in the total amount of protein in AM suggests that chronic protein insufficiency leads to susceptibility to infection and to macrophage activation but has no similar effects on PMN.


Effect of essential and nonessential fatty acids in complex mixture on fatty acid composition of liver lipids. Linoleate, linolenate, arachidonate, docosahexenoate and six other fatty acids were major components of 24 ester preparations fed as 5% of the diet for 60 days to groups of male white rats. The experiment was designed so as to provide that all major fatty acid components were independent of each other in the sense that the intake of each was poorly correlated with the intake of any of the others. Fatty acid compositions of liver lipids were determined and were related to the composition of the diet lipids. Linolenate and docosahexaenoate contents of diet and tissue revealed the same relationships reported previously from experiments in which individual pure acid esters were added to a fat-free diet. Linoleate, when fed in lipid mixtures, was more effective in raising the linoleate concentration in liver lipids than when fed alone, but this increase did not change the shape of the dose-response curve or the estimated nutritional requirement. Large amounts of fish oil in the diet tended to depress the arachidonate concentration in tissue lipids.


Effect of chronic hypovitaminosis A on water metabolism in the weanling rat. To study water imbalance reported to occur in vitamin A deficiency, chronic hypovitaminosis A was produced in 7-week old rats by feeding deficient or adequate vitamin A (12 or 256 mug/kg body weight/day, respectively) for a comparison period of 6 weeks. In the case of the deficient rats, these were partially depleted of their vitamin A stores prior to feeding the 12 mug intake. At the termination of the comparison period, the deficient rats exhibited elevated cerebrospinal fluid pressure and lower plasma and liver vitamin A concentrations. Based upon kinetics of a single intrajugular injection of 3H2O and 14C-inulin, total body water, extracellular water and renal clearances were lower in vitamin A deficient rats. However, when these criteria were expressed on a body weight basis, there were no significant differences. The turnover of total body water was reduced in the hypovitaminotic A rats.  The results are discussed in terms of an inhibitory effect of vitamin A deficiency on growth.


Pulmonary function in perlite workers.

Pulmonary function in perlite workers. Pulmonary function was studied in 117 men employed in three plants engaged in the mining and processing of perlite. Of these, 38 had been employed for ten years or more; 18 for 15 years or more and four men for 20 years or more. Review of chest films confirmed previous studies which showed no changes indicative of pneumoconiosis. Measurement of forced vital capacity (FVC) by Jones Pulmonor and by Collins 9-liter spirometer did not show reductions correlated with length of exposure, after effects of cigarette smoking had been taken into account. There was instead a slight increase in FVC associated with years in the perlite industry. The distribution of individuals with FVC below 80% of predicted also showed no association with duration of perlite exposure. Although there were slight reductions in forced expiratory volume in one second (FEV1) and in FEV1/FVC% which were associated with years in the perlite industry and which could not be explained by cigarette smoking, these reductions were not statistically significant. In summary, the population of men available for study in the major perlite-producing area of the United States, who have worked for periods up to 23 years, showed no evidence of pneumoconiosis by chest radiography or by measurement of forced vital capacity. Nevertheless, continued control of dust to ensure exposures below nuisance dust levels is essential. Medical surveillance should also continue with records being retained for periodic reevaluation.


Smoking characteristics by type of employment. Smoking habits are examined in a probability sample of 75,827 American men and women. The data was obtained from The 1970 Household Interview Survey conducted by The National Center for Health Statistics. There are pronounced differences in prevalence intensity, kind, cessation of smoking related to type of employment. Occupations tend to be more of a factor in white males, where occupational choice is least encumbered, than in black males or in females. While blacks uniformly smoke with greater prevalence, they are much lighter smokers than whites. Employed women tend to smoke with prevalence approaching males for many occupations. Prevalence of smoking almost uniformly is highest among blue collar occupations and lowest among professionals, managers, and proprietors.


Safety and the problem employee.

Safety and the problem employee. Approximately 5 to 7% of workers in any large employee population can be described as having borderline acceptable work performance and fluctuating emotional stability. This subpopulation of employees can be characterized as suffering from attitudinal disturbances ranging from mild to severe. At times physical illness can be an important contributing factor, but more commonly the sole attribute these individuals possess is a negative attitude toward work. It is this sub-group of problem employees which contribute the largest percent of unsafe acts leading to the greatest numbers of industrial accidents in the work community. Identification of this sub-group in the work force and utilization of selective physician-management counseling are definite steps that can be taken to improve the overall performance of the work group. Above average frequency of industrial accidents as well as above average rates of short term absence are significant job performance characteristics which correlate highly with identification of the problem employee. The mutual interchange between supervisor and employee of the counseling session provides a significant contribution to the employees coping mechanism. In our experience 85% of employees improve their job performance following counseling without the need for additional disciplinary action. A follow-up review of job performance with the employee is held within three to six months to reinforce the corrective steps already begun. Cost savings resulting from this approach can be significant. In this study a cost savings of $185 per employee per year was generated in a small isolated work group between 1972 to 1975. The calculation of direct dollar savings foe improvement in lost time statistics probably represent minimal cost savings, as some studies assume the total cost for sickness absence are 2-1/2 times the direct cost.


Occupational differences in rates of lung cancer. Lung cancer rates in Los Angeles County were reviewed for different occupations and industries. Employment groups found to be at excess risk who have not been previously implicated included roofers, dental lab technicians, decorators, nonautomotive mechanics, photoengravers, clothing ironers, electricians, bar and restaurant managers, janitors: and workers in the radio-TV brooad-casting, dairy, leather, food and drink, bakery, and auto repair industries. Mo lung cancer in Los Angeles County had exposure to asbestos, polycyclic aromatic hydrocarbon compounds (PAH), or both.