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Etomidate was compared with thiopental with respect to preventing loss of brain high energy metabolites and accumulation of lactate during 20 min of hypoxemia (Pa2 of 16-19 mmHg) in rats with unilateral carotid artery ligation. Male Sprague-Dawley rats, anesthetized with halothane and nitrous oxide (N2O) in oxygen were randomly assigned to one of six groups. A normoxic control group which received 70% N2O in oxygen, a hypoxia group received no iv drug treatment (hypoxia-N2O), and four iv drug treatment groups (N2O was replaced by 70% nitrogen at the start of drug administration). The iv drug groups were treated as follows: hypoxia-etomidate low dose (1 mg.kg-1 iv followed by an infusion at 0.35 mg.kg-1.min-1); hypoxia-etomidate high dose (1 mg.kg-1 then 1.3 mg.kg-1.min-1); hypoxia-thiopental low dose (15 mg.kg-1, then 1.5 mg.kg-1.min-1); and hypoxia-thiopental high dose (15 mg.kg-1, then 5 mg.kg-1.min-1). After hypoxia or a corresponding period in the normoxic group, the brains were frozen in situ for later biochemical analysis. Blood was obtained prior to and at the end of hypoxia and analyzed for glucose. Brain metabolite concentrations on the side ipsilateral to the ligated carotid artery in the normoxia-N2O group were adenosine triphosphate (ATP), 2.76 +/- 0.1, phosphocreatione (PCr) 3.88 +/- 0.12, lactate 2.34 +/- 0.16, and glucose 3.56 +/- 0.28 (mumole.g-1 wet weight, mean +/- SE). There was no significant decrease in ATP in any of the hypoxia groups. PCr decreased by 45% (compared to normoxia-N2O) in the hypoxia-N2O group.(ABSTRACT TRUNCATED AT 250 WORDS)

Freeze-fracture replicas have been prepared from two fast-acting vertebrate muscles (frog sartorius and rabbit sacrospinalis) and are described with particular reference to the distribution of intercalated particles in the plasma membrane, T-tubule and SR cisternae. Orthogonal assemblies of small particles are present on the A face plasma membrane in each instance, and their distribution (in sartorius) is found to be random with respect to the underlying myofibrillar sarcomere repeat. Such assemblies are not present on A or B faces of T-tubule or SR cisternae. Asymmetric particle distribution is described for fracture faces of the T-tubules and SR: the profuse particle packing of the SR A face is uniform from terminal cisternae to medial fenestrated collar. Intercalated particles are present on A and B faces of T-tubule fractures: more commonly on the latter. These results are compared with studies on insect muscles, and a comparative approach to further studies on the correlation between membrane structure and function is discussed.

The ventral, postsynaptic membranes of the electroplaques of Narcine were examined for structures corresponding in location, numbers, position and form with nicotinic acetylcholine receptor-channel molecules. Electron micrographs of conventionally fixed material showed that the thickened outer lamina of these membranes contained about 6100 stained structures/μm 2 ; and calculations from this packing density and the estimated area of postsynaptic membranes/g tissue yielded a total number of structures within a factor of two of the number of receptor molecules/g determined from the binding of alpha-bungarotoxin. Examination of tissue prepared with a tannic acid/glutaraldehyde fixative revealed that the structures were uniform in character, cylindrical in shape, transmembrane in position, and that each contained a central core. Their diameter matched that of isolated receptor molecules, and their size can account for most of the receptor protein. We conclude that these receptor molecules are largely intramembranous, cylindrical and exhibit transmembrane pores.

In the early decades of the twentieth century, the `Glasgow School' of D. N. Paton, L. Findlay and E. P. Cathcart developed a distinctive approach to the scientific study of nutrition and to the social application of scientific knowledge. They adhered to the practice of chemical physiology, which they defended against the encroachment of a reductionist, modernizing biochemistry. In the face of rival claims from the emergent professional biomedical scientists, Paton, Findlay and Cathcart upheld a more traditional view of medical education and the relationship between the doctor and the laboratory scientist. They also lent their medical and scientific authority to the then Government's policy of minimal intervention in the condition of the poor, employing arguments hostile to rational, scientistic reform. Using Karl Mannheim's concept of `styles of thought', the paper characterizes the rhetoric of the Glasgow School as being `conservative' in style. It is suggested that Paton, Findlay and Cathcart used conservative thought as a useful tactic in the defence of a wide variety of social interests. This study of the Glasgow School is intended as a contribution to the history of physiology, biochemistry and nutrition, to the understanding of the interactions between the laboratory and the clinic, and to the literature on styles of thought.

Interfaces have been formed between stabilized zirconia and calcia doped lanthanum chromite by pressing at 1500°C. Characterisation of the interfaces with scanning electron microscopy and X-ray microanalysis shows the presence of an intermediate layer at the junction. This layer has an important role in the formation of a mechanically strong bond. The application of ceramic electrodes in high temperature furnaces is discussed.

It has previously been demonstrated that peripheral blood leucocytes of the nurse shark (Ginglymostoma cirrhatum) are capable of in vitro chemotaxis. In the present study we have identified the chemotactic cells as the shark granulocyte and monocyte-macrophage. Chemotaxis assays were set up in blind well chambers. Cells migrating into the filter in a chemotaxis assay were identified morphologically by transmission electron microscopy. Migration, in response to LPS-activated rat serum, was accompanied by change in cell shape and reorganization of the cytoskeleton. Ultrastructural changes included formation of lamellipodia with cell polarization, submembranous accumulation of microfilaments at points of plasma membrane contact with filter surfaces, densification of the membrane at these points of engagement, appearance of bundles of intermediate filaments extending into the protruded lamellipodia, and presence of oriented microtubules in the cytoplasma (cellular cortex). The phagocytic and chemotactic properties of the shark granulocyte and monocyte-macrophage points to their being structural and functional equivalents of the mammalian neutrophil and macrophage.

The authors examined the effects of large intravenous doses of sufentanil (5-160 micrograms/kg) on cerebral blood flow (CBF) and cerebral metabolic rate for oxygen (CMRO2) in rats. CBF and CMRO2 were measured by a modified Kety-Schmidt technique using 133Xenon washout. Progressive decreases in CBF and CMRO2 occurred in animals receiving sufentanil. The maximum decrease was 53% and 40% for CBF and CMRO2 respectively, at a dose of 80 micrograms/kg. The values for CBF and CMRO2 in this group were 105 +/- 10 ml X 100 g-1 X min-1 (mean +/- SEM) and 6.5 +/- 0.5 ml X 100 g-1 X min-1, respectively, compared with 226 +/- 28 ml X 100 g-1 X min-1 and 10.9 +/- 1 ml X 100 g-1 X min-1 in the control group, which received N2O 70% in oxygen. Larger doses of sufentanil did not cause further significant changes in CBF and CMRO2. Sharp waves appeared on the electroencephalogram (EEG) of all the animals following sufentanil injection, and some animals had EEG changes develop consistent with seizure activity. This seizure-like activity appeared to consist of a single episode of short duration in the groups receiving 5, 10, and 20 micrograms/kg sufentanil. The incidence and frequency of seizure activity increased in the groups receiving higher doses of sufentanil, although the duration of seizures was still short. The results of this study indicate that sufentanil causes a significant decrease in CBF and CMRO2 similar to that previously reported for fentanyl, and high doses of sufentanil may cause frequent seizure-like patterns appearing on EEG.

The contractility of guinea pig ileum and frog skeletal muscle is inhibited in solutions containing 0.4 to 2.5 M formamide (FMD). Contrary to mammalian vis ceral muscle, this blocking action is not reversed when frog muscles are transferred back to isotonic Ringer's after FMD treatment. Under these conditions the water content of the skeletal muscles is markedly increased and electronmicrographs show a swellingof the transverse tubules. These changes are not observed when frog muscles are transferred to ethylene glycol solutions that are isosmotic with the FMD containing Ringer's solution. In addition, over 50% of the contractility is recovered in these muscles. These observations provide direct evidence of the occurrence of an osmotic shock in frog muscles transferred from FMD solutions to isotonic Ringer's. It is concluded that the resulting alterations in the triad structure and function are re sponsible for the irreversibility of the FMD uncoupling action in these muscles.

The protective effect of barbiturates in cerebral ischemia has been proposed to be related to inhibition of lipid peroxidation. The present in-vitro study was undertaken to test the efficiencies of different barbiturates to inhibit peroxidative reactions in brain tissue, and to compare their effects with established free radical scavengers (chlorpromazine and promethazine). Cortical homogenates, prepared from decapitated rats, were incubated at 37 C with 5 per cent O2 (in N2) in the presence of ferrous sulfate (0.01 mM) and ascorbic acid (0.25 mM). During incubation there was extensive lipid peroxidation in the tissue, as evidenced by appreciable production of thiobarbituric acid-reactive material (TBAR), 1.2 μmol malondialdehyde g−1 cortex in one hour. Thiopental (1.0 mM) caused a 96 per cent inhibition of TBAR production, while other barbiturates (in the same concentrations) had only small (methohexital) or no (pentobarbital and phenobarbital) inhibitory effect. The inhibition of TBAR production by 1.0 mM thiopental was similar to that found with 1.0 mM chlorpromazine or 0.1 mM promethazine. The inhibitory effect of thiopental on lipid peroxidation was confirmed by analysis of fatty acids and phospholipids. Thiopental prevented the peroxidative degradation of polyenoic (20:4, 22:6) fatty acids and of ethanolamine phosphoglyceride that otherwise occurred during incubation. The marked differences between the tested barbiturates with respect to their abilities to inhibit lipid peroxidation in vitro are at variance with the fact that all of these barbiturates have been reported to protect the ischemic brain in various situations in vivo. The results imply that the protective effect of barbiturates under such conditions is unrelated to inhibition of lipid peroxidation, and suggest that instead they may act by other mechanisms.

The incisive detection of bioenergetic insufficiency in an organ of known workload by P MRS is noninvasive and nondestructive, and in some cases the portion of the organ involved can be determined, particularly if both PCr and ATP are depleted. The fractional loss of ATP and hence the relative volumes of viable and "metabolically dead" tissue are thereby evaluated. In addition, the value of P MRS in following a therapy complements its value in diagnosis as this has been demonstrated in cases followed over 6 months to three years. The fact that deficiencies of the enzymes and substrates of oxidative metabolism can be detected by P MRS affords a global overview of energy metabolism that can be a key to rapid diagnosis. The distinction of the enzyme and/or substrate deficiency, while not directly indicated by steady state P MRS, can be identified by use of the "Crossover Theorem" and its impact upon blood and tissue levels of substrates (including oxygen). In the case of neonatal systemic hypoxia, there is no doubt about which of the equations applies, and similarly in metabolic disease, a glutaric acid urea is a direct consequence of the crossover response of metabolism and signifies that an enzyme deficiency may be involved. Furthermore, the clinical danger of a high Pi/PCr value is clarified by our observations, both from the animal models and from the theory, the high clues; i.e. 2 and over, suggest work stresses near the capability of oxidative metabolism and imminent failure of the negative feedback afforded by metabolic regulation, particularly ADP control of oxidative metabolism. This control is lost because of the fall of phosphocreatine to the point where creatine kinase is no longer in equilibrium, leading to the loss of ATP and its conversion to large amounts of ADP and its breakdown products. ATP then stimulates glycolysis and results in a massive lactic acidosis. At the same time, the low thermodynamic capability of glycolytic metabolism is unable to prevent irreversible ion disequilibration, water movements, edema, and eventually rupture of the cell membrane. The pathway of resynthesis of ATP is then tortuous, particularly as AMP is deaminated and adenosine is converted eventually to hypoxanthine. Thus, NMR reports that metabolic control is operating in the region where homeostasis of biochemical parameters is feasible. It further reports regions where the metabolic control is susceptible to failure and most aggressive clinical care is required.

1. The changes in the consistence of the spine-test articular capsule, or ligament, of the primary spines of Eucidaris tribuloides induced by acetylcholine (ACh) have been studied. Two complementary techniques were used: (a) “forced-vibration”, which detects variations in the stiffness of the ligament along a single diametral plane; and (b) “forced-rotation” which records the spatial distribution of those changes. 2. ACh (1 μM to 1 mM) caused a rapid increase in the resistive force opposed by the ligament to passive stretching. Similar effects were elicited by several monoquaternary, N-substituted derivatives of trimethylammonium. 3. The opposite effect, i.e. softening, was induced by decamethonium, dimethylphenylpiperazine, and 2-ketoamyltrimethylammonium. 4. The involvement in these effects of ACh-binding groups with pharmacological properties similar to those of the “anionic sites” of nicotinic ACh receptors is suggested.

The pediatrician should be aware of the fact that nearly all drugs used in the therapy of lactating women may be found in varying amounts in breast milk. Mothers who must take antithyroid drugs, chloramphenicol, lithium, methadone, most anticancer drugs, radioactive pharmaceuticals and antiinfective agents such as the tetracyclines and metronidazole should not nurse their infants while receiving therapy. It has been our experience that in most instances safer alternative drugs may be selected after discussions with obstetricians, family physicians, and internists. The use of other drugs merits a certain degree of caution; nursing the infant before a dose is given may help to minimize exposure to the infant. Interruption of breast-feeding should be infrequent.

Septate junctions have been studied in the hind-gut of Periplaneta americana, Incisitermes schwartzi and Thermobia domestica. The topographical disposition of intercellular septa revealed by lanthanum impregnation corresponds well with that of particle rows seen in freeze fracture preparations. However, there is no precise correspondence between the undulations of septa and the disposition of particles within a single row. The spacing of particles is variable and generally less than that of the undulation periodicity of septa. On the other hand, the disposition of septa, and of the rows of particles that correspond to them, appears to be variable: sometimes rectilinear and in close parallel, these may curve or form series of 'finger-print' loops. Moreover, the septa are evidently not deployed as continuous ribbons around the cell since intrruptions are freuqently observed. In addition to their mechanical role in intercellular cohesion, septate junctions apparently ensure a more or less complete closure of the intercellular space (i.e. provide a permeability barrier) and thus play a role comparable with that of tight junctions in epithelia of vertebrates.

Spine catch ligaments of a sea urchin Arbacia punctulata were extended under constant load. Ligaments from an undisturbed animal may show any extension rate from zero (catch state) to rapid extension to failure. Replacing the preparation bath with CA(2)- and Mg(2+)-free sea water reversibly abolishes the catch state. The fine structure of the outermuscle layer and inner ligament cone associated with the spine base is described. The unstriated paramyosin muscles bear thin flanges and form compact interlocking rows. Subsurface cisternae are associated with the plasma membrane. The muscles are innervated by glia-free axons ending in bulbous terminals containing lucent synaptic vesicles. The ligament comprises cylindrical bundles of collagen fibrils: one or more minute muscle fibers (paramyosin) lie parallel with and closely adjoining each bundle. The mean diameter of these muscles is 0.3 micrometers and they occupy 2-3% of the ligament's cross-sectional area. Axons containing electron-opaque secretory droplets accompany the muscles between the collagen bundles: the cell bodies of these neurones generally lie on the outer surface of the ligament. When an urchin points a spine, the ligament on the side of the contracting spine muscle shortens but does not buckle. A function of the intraligamental muscles is to effect this non-buckled shortening. The catch mechanism (which reside entirely within the ligament) may be due either to the intraligamental muscles and/or to a locked polymer mechanism in which matrix molecules between collagen fibrils are reversibly cross-linked by divalent cations.

The effect of grain size on the electrical properties of polycrystalline YBa 2 Cu 3 O 7 − δ has been investigated. A strong decrease in the critical current density has been observed when an average grain size of 15 μm is exceeded. Large grains promote microcracks due to anisotropic volume changes during cooling from the sintering temperature. This causes a reduction in the effective current-carrying cross section of the material. Ultrasonic measurements were used to confirm a significant increase in the microcrack density for large grained samples.

We have proposed that tissue metabolic failure during hypoxia or ischemia is related to the microheterogeneous distribution of tissue oxygen and not to failure of the creatine kinase equilibrium. This theory is based on the concept that sharp oxygen gradients exist in rapidly metabolizing tissue and that shifts in these gradients can place specific cells at risk for metabolic death while relatively adjacent cells escape unharmed; cells that are unharmed meet the steady-state requirements (V less than Vmax), those at risk do not (V greater than Vmax). Though it would seem that confirmation of such a hypothesis would require metabolic delineation at a high resolution, we have shown how 31P MRS provides information supporting this hypothesis. This possible use of MR spectroscopy to define microheterogeneous events suggests further clinical possibilities for this instrument in defining the rate of cell loss and the response to therapeutic interventions.

Zirconia has been bonded to lanthanum chromite by co-firing. The ceramic bodies are joined during sintering with an applied pressure of less than 0.1 MPa. This technique facilitates the formation of a junction phase which involves the impurity silica. During firing at 1500°C, silica is driven from zirconia and lanthanum chromite to the junction region, where it combines with calcia as well as other components to form a liquid phase. The liquid phase relaxes stresses due to differential shrinkage of the two bodies and, on cooling, solidifies, thus bonding lanthanum chromite to zirconia.

The distribution of microtubules and mitochondria in central axons of an insect (Periplaneta americana) is assessed by comparison between counts on micrographs and computed axon random ‘models’. These studies show that the observed multiple association of microtubules with individual mitochondria is statistically highly significant. Electron micrographs of thin sections show that linkage is effected by physical cross-bridges, possibly comprising components from the microtubule and mitochondrion. Linear particle arrays are described on the outer mitochondrial membrane in freeze-fracture replicas, and tentatively related to the bridges seen in thin sections. The results are discussed in terms of proposed roles of microtubules in neurons and other cells.

The risk of aspiration during induction of anaesthesia in patients with oesophageal disease is not well defined, and controversy exists with respect to patients who have undergone pharyngeal-gastric colon interposition. Excellent gastrooesophageal competence has been documented in many of these patients, and propulsive peristalsis has been demonstrated in interposed colonic segments, suggesting that aspiration risk is low. This report, however, describes recent anaesthetic experiences in two patients with colon interpositions and shows that these patients may have markedly redundant interposed segments that retain food or other particulate residue and, thus, present a significant risk of particulate aspiration. Awake intubation may be the best approach to avoid aspiration in these patients.

The complement system of the nurse shark was investigated. Six functionally pure components were isolated from a single serum sample. Sequential reactions of the components with sensitized sheep erythrocytes resulted in membrane lesions indistinguishable from the "holes" caused by guinea pig complement.

Gross ultrastructural and histochemical details of the integumental milk glands of the tsetse fly Glossina morsitans have been examined during the pregnancy cycle. Structural evidence for protein secretion is found between Days 3–8 of the nine-day cycle: termination of activity is completed on the day of parturition. Onset of lactation is synchronized with the eclosion of the first instar larva. The changes in cell volume (notably in the extracellular reservoir) occurring throughout the pregnancy cycle are illustrated in electron micrographs, and a one hundred-fold volume increase in the reservoir volume between the inactive phase and the active period is illustrated and discussed in terms of membrane modulation of the limiting membrane of the reservoir. Intracellular membrane changes during the cycle, particularly the development of extensive ER arrays in the actively secreting cell, are illustrated and discussed. It is suggested that cytoplasmic microtubules play a part in maintaining the form of the distended secretory cell, at the height of secretory release and storage. Histochemical observations on the milk secretion, and the contents of the larval gut are presented.

Effective Medium Percolation Theory can be used to predict the measured conductivity in two phase systems. It is shown that this theory can be applied to mixed phase, mixed alkali ion β aluminas if adequate account is taken of such factors as grain misorientation and ion distribution. The information obtained about the mixed alkali effect is in good agreement with existing experimental data.

In termites and roaches the well-defined rectal papillae each comprise a layer of columnar principal cells specialized for active transport and a layer of basal cells. The whole cell group is entirely surrounded by several series of flattened 'sheath cells' (formerly termed 'junctional cells') which abut onto the basal components of the papilla. The sheath cells secrete a specialized sclerified cuticle which forms the framework of the papilla. Their regularly pleated apical membrane is closely apposed to the cuticle and contains parallel and closely spaced rows of intramembranous particles. at this level, no subcuticular space is present and hence the space associated with the apical surface of the principal cells is defined as an isolated compartment. Typical septate junctions are present between the sheath and basal cells; however those linking adjacent sheath cells are structurally unusual: they extend to the basal surface rather than being restricted to the apical zone, are frequently interrupted and in replicas are represented by relatively short and irregularly oriented particle rows. Moreover, lateral sheath cell contacts display two further peculiarities: absence of an apical desmosomal ring and paucity of gap junctions. Structural observations suggest that the sheath cells isolate the principal cells from communication with the hemolymph, consequently enhancing their efficiency in water and ionic regulation. Comparable cells have been described in a number of insects, but the 'isolation' system presents varying degrees of complexity, for which an evolutionary scheme is proposed.

The disposition of the surface plasma membrane and its inwardly directed derivatives, corresponding to the T-system of other fibers, and of the corresponding sarcoplasmic reticulum (SR) elements has been examined in a dipteran asynchronous flight muscle ( Photmia regina ). The presence of uniaxonal neuromuscular junctions within clefts approaching the center of the fiber is described. The most conspicuous SR component is present in the dyads adjoining plasma membrane derivatives, but it is also sparsely represented elsewhere. The accessibility of the plasma membrane-limited compartments within the fiber to the ambient haemolymph, in the living insect, has been investigated by tracing the distribution of ferritin by the circulatory system. The proportion of fiber volume occupied by the T-system and SR components in asynchronous and synchronous muscle is compared and the functional implications of these proportions is discussed.

Lamellar body inclusions of the rat lung great alveolar cell (=Type II alveolar cell) have been studied by conventional thin sectioning and freeze-etching. The former confirmed previous reports that lamellar bodies are released into the alveolar space, and release inter alia tubular myelin, associated with lung surfactant. Replicas of fixed or unfixed freeze-etched material reveal the intracellular lamellar bodies as highly structured, in which lamellae may be concentric or disposed in parallel planar series. Fractured lamellae bear ca. 100 A particles, and linear sculpturing similar in spacing to extracellular tubular myelin. Transverse fractures show that lamellae are ca. 60 A in width, comprising two ca. 20 A components. The appearance of freeze-fractured and etched lipoprotein and phospholipid membranes is discussed, and it is proposed that the surfaces revealed within the lamellar body are associated with the elaboration of surfactant components.

The structure of peripheral nerves, and the organization of the myoneural junctions in flight muscle fibers of a beetle is described. The uniaxonal presynaptic nerve branches display the "tunicated" structure reported in the case of other insect nerves and the relationship between the axon and the lemnoblast folds is discussed. The synapsing nerve terminal shows many similarities with that of central and peripheral junctions of other insects and of vertebrates (e.g., the intra-axonal synaptic vesicles) but certain important differences have been noted between this region in Tenebrio flight muscle and in other insect muscles. Firstly, the axon discards the lemnoblast before the junction is established and the axon effects a circumferential synapse with the plasma membrane of the fiber, which alone shows the increased thickness often observed in both pre- and postsynaptic elements. Secondly, in addition to the synaptic vesicles within the axon are present, in the immediately adjacent sarcoplasm, great numbers of larger postsynaptic vesicles which, it is tentatively suggested, may represent the sites of storage of the enzymatic destroyer of the activating substance similarly quantized within the intra-axonal vesicles. The spatial relationship between the peripherally located junctions and the portion of the fiber plasma membrane internalized as circumtracheolar sheaths is considered, and the possible significance of this with respect to impulse conduction is discussed briefly.

Replicas of fractured chromaffin cells are indicative of a range of activities thought to characterize exocytosis, including attachment of secretory vesicles to the plasma membrane, fusion, extrusion of contents, and membrane retrieval. Exocytosis sites are abundant on stimulated cells but are infrequent when calcium is omitted from the system.

The fine structure of myoepithelial cells of the proventriculus of a marine annelid ( Syllis spongiphila ) is described. The contractile system of these muscle fibers includes a single medial Z band. The thick filaments possess a ~140 A paramyosin-like periodicity, but the filament disposition in these cells corresponds to that of other striated muscles, and actin orbitals in the A band number up to 20. The distance between the centers of the two H bands in the largest cells is ca . 40 µ Dyads involving T-system invaginations and isolated vesicles of the sarcoplasmic reticulum are situated at all sarcomere levels. Insertions of the contractile material onto invaginations of the inner and outer cell surfaces are described. Presumed polyaxonal neuromuscular junctions are established across wide synaptic clefts and include terminals with spherical and non-spherical synaptic vesicles. Inclusions occupying the core of each muscle cell appear to be rich in magnesium.

The fine structure of fibrillar flight muscle of the mature adult beetle Tenebrio molitor is described. Although the very high frequency of contraction of fibrillar muscle has previously been in part accounted for as the result of mechanical specialization of the wing-bearing segment rather than of a correspondingly high rate of motor impulse supply, the problem of the nature of the pathway by which excitation is conducted into these large fibers remained. Therefore, particular attention has been given to the disposition and relationships of the plasma membrane and sarcoplasmic reticulum in this tissue. The invading tracheoles draw with them a sheath of plasma membrane from the surface to all depths in the fiber, and it is suggested that these sheaths, together with the extensive tubular arborisations arising from them, reduce the maximum plasma membrane-to-fibril distance from the radius of the fiber to a value of less than 2 µ. The evidence presented here confirms Veratti's contention that in fibrillar muscle the "reticulum" is associated with, though entirely distinct from the fibrils. Unlike other muscles so far examined, these flight muscle fibers contain a plasma membrane reticulum only, but it is possible that elsewhere the general "sarcoplasmic reticulum" includes a component derived from the plasma membrane, likewise acting as the pathway for inward conduction of excitation. Profiles of the internalised plasma membrane in Tenebrio showing the usual triple-layered 25-25-25 A organization are frequently seen, in sections, in close association with isolated vesicles (defined by "simple" 50 A membranes) which are here considered to represent, in vestigial form, the portion of the sarcoplasmic reticulum which in other types of muscle is complex and highly developed. Such associations, in Tenebrio, between these two dissimilar elements are here termed "dyads" and the possible morphological and functional homology between these and the "triads" of other types of fiber is considered.

The organization of the luminescent organ of an adult firefly has been studied with the electron microscope, and particular attention has been given to the disposition of nerve terminals within the organ. The cytological structure of the cells of the tracheal system, the peripheral and terminal axons, the photocytes and the cells of the dorsal ("reflecting") layer is described. Previous observations on the peripheral course of nerve branches alongside the tracheal trunks at the level of the dorsal layer and photocyte epithelium have been confirmed, and specialised nerve endings containing axoplasmic components structurally identical with "synaptic vesicles" and "neurosecretory droplets" have been identified, not in association with the surface of the photocytes, but lying between the apposed surfaces of two components of the tracheal epithelium: the tracheal end-cell and the tracheolar cell. These cytological findings are discussed in terms of available biochemical and physiological evidence concerning the mechanism of light emission in the firefly, especially with respect to the possible role of chemical "transmitter" action in triggering a response in a luminescent effector system.

Pure preparations of Trypanosoma brucei , free from plasma and cellular components were isolated from rat blood, and concentrated into loose pellets by low-speed centrifugation. Pellets were either processed for thin sectioning as a control for general morphology, or glycerol-treated after glutaraldehyde fixation for preparation of freeze-fracture replicas. Concentration of cells of 50,000–100,000/mm 2 of sectioned or fractured surface facilitated identification of fracture faces of the cell body, invaginated flagellar pocket and flagellum. Particle distribution and A and B faces of these regions of the cell are described. A collar of B face particles occurs around the neck of the flagellar pocket, possibly associated with a junction controlling ingress of ingested materials to coated vesicles formed along the membrane defining the pocket. A and B faces of the flagellum and adjoining surface of the cell body have shown that the only intra-membrane specialization corresponding to the miniature ‘maculae adherentes’ described previously in thin sections is probably an uninterrupted series of small clusters (3–6) of 80 A particles on the A face of the flagellar membrane. It is proposed that these arrays represent attachment points for strands linking the axoneme and paraxial rod to the flagellar surface, and are not directly concerned with the physical adhesion of the flagellum to the cell body surface—a linkage that appears to be established within the extracellular gap between these apposed surfaces of the cell. The potential use of freeze-etching in further study of the external antigens of the infective cell is discussed.

The organization of the indirect flight muscle of an aphid (Hemiptera-Homoptera) is described. The fibers of this muscle contain an extensive though irregularly disposed complement of T system tubules, derived as open invaginations from the cell surface and from the plasma membrane sheaths accompanying the tracheoles within the fiber. The sarcoplasmic reticulum is reduced to small vesicles applied to the T system surfaces, the intermembrane gap being traversed by blocks of electron-opaque material resembling that of septate desmosomes. The form and distribution of the T system and sarcoplasmic reticulum membranes in flight muscles of representatives of the major insect orders is described, and the extreme reduction of the reticulum cisternae in all asynchronous fibers (to which group the aphid flight muscle probably belongs), and the high degree of their development in synchronous fibers is documented and discussed in terms of the contraction physiology of these muscle cells.

An electron microscopic investigation of the Malpighian tubules of a leaf hopper, Macrosteles fascifrons, shows that these organs comprise three quite distinct cell types, and the structure of these and of the mid- and hindgut epithelial cells is described. In particular, a comparison is made between the organization of the basal and apical surfaces of cells in the Malpighian tubule and in the vertebrate kidney, and it is suggested that similarities between these excretory epithelia reflect functional parallels between them. While the midgut and one region of the Malpighian tubule bear a typical microvillar brush border, elsewhere in the tubule and in the hindgut the apical surface bears cytoplasmic leaflets or lamellae. The sole solid excretory material of these insects consists of the brochosomes, secreted by cells of one region of the Malpighian tubule. The structure, geometry, and development of these unusual bodies, apparently formed within specialized Golgi regions, has been investigated, and histochemical tests indicate that they contain lipid and protein components.

The distribution of ATPase activity in the asynchronous flight muscles of Calliphora erythrocephala (Diptera) was studied at a fine structural level, using preparations of teased fibers, both unfixed and after brief fixation in hydroxyadipaldehyde, incubated in a medium for the histochemical demonstration of myosin or actomyosin ATPase. In relaxed fibrils, activity was found confined to the A bands and was absent from the H zones as well as from the Z and I band regions. At high magnification, deposits of final product, lead phosphate, appeared primarily related to the thick filaments, or to short lateral extensions from them. Evidence was gathered which indicated that this enzyme activity was that of a triphosphatase which did not act on dinucleoside or non-nucleoside substrates.

1. 1. The time dependence of the fluorescence enhancement of 1-anilinonaphthalene-8-sulphonate after addition to haemoglobin-free human erythrocyte ghosts was studied in 150 mM NaCl, 10 mM sodium phosphate (pH 7.0) at 25 °C. 2. 2. Enhancements were analysed in terms of “fast”, “medium” and “slow” phases. 3. 3. Ghost samples shown to be at least partly resealed towards Na + and/or osmotically responsive display a slow phase (half-time about 80 or 120 s depending on conditions at haemolysis). The medium phase (half-time about 14 s) is characteristic of physically intact membranes in a non-resealed state. The fast phase (half-time less than instrument response time) always comprises at least 50% of the total enhancement. 4. 4. 1-Anilinonaphthalene-8-sulphonate fluorescence parameters suggest that most probe binding sites are similar, and that they are not involved in membrane changes leading to resealing. 5. 5. It is proposed that 1-anilinonaphthalene-8-sulphonate sites are only distinguished by location on the extracellular or intracellular side of a membrane 1-anilinonaphthalene-8-sulphonate premeability barrier. Diffusion of 1-anilinonaphthalene-8-sulphonate across the barrier produces the observed medium or slow phases, depending on the state of the membrane.

An electron-microscopic examination of bone marrow mitochondria derived from 10 patients before and after chloramphenicol (CAP) therapy has shown that CAP induces an ultrastructural modification resulting in an increase in the density of the mitochondrial matrix. These changes resemble the condensed mitochondrial configurations which have previously been interpreted in terms of electron transfer and oxidative phosphorylation. However, in the concentrations employed in this study, CAP has no effect on mitochondrial respiration or on oxidative phosphorylation, but is a potent inhibitor of mitochondrial protein synthesis. Evidence relating this effect of the drug to its myelotoxicity has been supported by a comparative study demonstrating lack of effect of a drug such as tetracycline which is not known to be myelotoxic, and the excel lent correlation between the extensiveness of mitochondrial changes in the marrow and the serum level of free CAP. The results were confirmed in a parallel study on insect flight muscle mitochondria, in which the metabolic state under which the drug is administered can be controlled and where the regular disposition of the mitochondrial cristae provides an ideal model for the study of configurational changes.

The detailed structure of the cockroach spermatheca is described and discussed firstly as an example of an insect integumentary gland, and secondly, from the standpoint of its role in reproduction. The gland comprises a cortical rank of separate secretory units, each associated with an epithelial duct cell responsible for receiving secreted materials and transporting them through the cuticular intima lining the reproductive tract. Secretory activity is cyclic, and the probable mode of elaboration and release of secretory material is described, together with the fine structure of the markedly differing intimas associated respectively with the glandular and conducting units.

The distribution of esterase activity in the last abdominal ganglion, the connectives and the cereal nerves of the cockroach Periplaneta americana has been investigated cytochemically. Activity of an unspecific eserine-insensitive esterase (or esterases) has been found in glial elements in these regions of the nerve cord. In addition, sites of cholinesterase (eserine-sensitive) activity have been found in association with (a) the glial sheaths of the axons in the cereal nerves and connectives, (b) the glial folds encapsulating the neuron perikarya in the ganglion, and (c) in localized areas along the membranes of axon branches within the neuropile, often flanked by focal clusters of synaptic vesicles. These results are discussed with particular reference to the previously reported insensitivity of the insect nerve cord to applied acetylcholine, and to the probable existence of a cholinergic synaptic mechanism in the central nervous system of this insect.

The organization of the corpora cardiaca and corpora allata of the female alfalfa weevil, Hypera postica, generally parallels that reported for other insects with extrinsic neurosecretory axons, intrinsic neurosecretory cells, and interstitial or glial cells appearing in both glands. Connecting the brain with the cardiacum are the extrinsic neurosecretory axons containing granules between 600 and 2200 A. Granules with a diameter of up to 4000 A are found in the intrinsic secretory cells of the corpus cardiacum. From the lobed corpus cardiacum, axons extend along a short nerve trunk into the ovoid corpus allatum. A characteristic of this gland is the presence of a layer of axons, ensheathing most of the corpus allatum and situated beneath an external basement membrane. These axons are believed to have their origin in the protocerebral neurosecretory cells. Although the c. allatum is known to be engaged in the release of hormonally active material, the cytoplasmic organization does not strongly reflect such activity. The glands of the diapausing weevil appear similar to those of the active weevil with a reduction in cytoplasm and a consequent folding of the plasma membrane.

The fine structure of a spider myo-apodeme junction is described, and discussed in terms of other arthropod muscle attachments. This is contrasted with the situation in the venom gland, equipped with muscle fibers that control expulsion of the secreted material. The latter involves a cell-free collagenous matrix, lying between the muscle cells and the sheath of the gland. As in other arthropods, skeletal fibers are attached to the apodeme cuticle via specialized epidermal cells, containing oriented microtubules. Interdigitations between these cells and muscle, basally, and cuticle, apically, are described. Extracellular tonofibrillae described elsewhere are inconspicuous in the apodeme cuticle.

The electrophysiological properties and structure of heart muscle fibres of the lobster myocardium have been investigated. Discontinuities were observed in the expected decrement of electrotonic potentials in a study of the passive membrane properties of the muscle. Injection of Procion yellow revealed transverse barriers to dye movement, identified in electron micrographs as intercellular junctions. Unlike the intercalated discs of the vertebrate myocardium, which these regions superficially resemble, nexus regions of `close' or `gap' junctions are absent. The intercellular cleft is generally 400 A in width, locally reduced to 75-100 A The functional implications of these findings are discussed. Cardiac myoneural junctions, which include regularly repeating structures extending into the synaptic cleft from the postsynaptic membrane, are described.