bluuebunny/crossref_metadata_2025 huggingface dataset:
CHANGES IN HISTOCHEMICAL PROFILE OF RAT RESPIRATORY MUSCLES IN HYPO‐AND HYPERTHYROIDISM
Authors: Johnson M. A. , Olmo J. L. , Mastaglia F. L.
Published: December 2014

Rat respiratory muscles underwent considerable changes in histochemical fibre type profile in response to hypo‐ and hyperthyroidism. Hypothyroidism increased the proportion of type 1 slow oxidative fibres in diaphragm and to a lesser extent in intercostal muscles. Hyperthyroidism resulted in a decreased proportion of type 1 fibres in both diaphragm and intercostals. These changes were broadly comparable to those reported previously in rat limb muscles. In normal rat respiratory muscles, the type 1 fibres were characterized by very high levels of β‐hydroxybutyrate dehydrogenase which was thought to contribute to the fatigue‐resistance of these muscles. The type 2B fast glycolytic fibres, and to a lesser extent type 2A fast oxidative fibres, contained high levels of mitochondrial α‐glycerophosphate dehydrogenase, an enzyme known to be specifically affected in dysthyroid states. The implications of the observed changes in fibre type profile with respect to the oxidative metabolism of rat respiratory muscles are discussed.
TRANSPORT OF LEUCINE BY THE SMALL INTESTINE OF LEAN AND GENETICALLY OBESE (ob/ob) MICE
Authors: Morton A. P. , Hanson P. J.
Published: December 2014

Transport of leucine by the small intestine of obese (ob/ob) mice has been compared with that by intestine of lean controls at various stages in the development of the syndrome. At 10 weeks of age, when hyperphagia and hyperinsulinaemia are at their peak, transport (expressed per gram dry weight) of a physiological concentration of leucine (5 mM) by luminally perfused whole small intestine of obese mice was significantly lower both in vitro (−45%) and in vivo (−27%). Experiments involving fasting and long‐term partial dietary restriction of obese mice suggested that the reduction in leucine transport was probably not a consequence of hyperphagia. The absence of any difference between lean and obese mice in the kinetics of unidirectional influx of leucine across the brush border contrasted with the findings from the luminal perfusion experiments. This discrepancy could indicate that the effect of the (ob/ob) genotype on leucine transport was at a stage in the process of transepithelial transport distal to the brush border, perhaps that of movement across the basolateral membrane.
PROPERTIES OF MINIATURE POST‐SYNAPTIC CURRENTS AT THE TORPEDO MARMORATA NERVE‐ELECTROPLATE JUNCTION
Authors: Soria Bernat
Published: December 2014

The post‐synaptic conductance changes induced by spontaneous release of neurotransmitter on the Torpedo marmorata electroplates were studied by focal extracellular recording methods. It was found that miniature post‐synaptic currents (m.p.s.c.s) recorded on the innervated and non‐innervated faces of the electrocyte are opposite in sense and the distribution of amplitudes is bimodal. The bimodal distribution could reflect the presence of two populations of m.p.s.c.s (smaller and giant m.p.s.c.s). In the smaller m.p.s.c.s the distribution of the ratio (amplitude/decay time constant) shows two populations that probably represent areas with different receptor densities. The value of the mean open‐channel lifetime estimated from the decay time constant of the m.p.s.c. is 0·92 ± 0·67 ms (n = 319, temperature 20 ± 1 °C). Prostigmine (10 µM) increases the amplitude, decay time constant and time to peak of the m.p.s.c. A decrease of temperature increases m.p.s.c. decay time, the activation energies found ranging from 8·0 to 12·6 kcal. mol−1. Increasing the external K+ concentration produces a decrease in the decay time constant. High concentrations of divalent ions, particularly Ca2+, increase the decay time constant of the m.p.s.c. Alkaline or acid bathing solution produces a decrease in the decay time constant. An almost total substitution of external Cl‐ by non‐permeant SO42− does not modify the time course of the m.p.s.c.
EFFECTS OF ADRENALINE AND NORADRENALINE ON GLUCOSE‐INDUCED ELECTRICAL ACTIVITY OF MOUSE PANCREATIC β CELL
Authors: Santana De Sa Sonia , Ferrer Rosa , Rojas Eduardo , Atwater Illani
Published: December 2014

The effects of adrenaline and noradrenaline on membrane potential and glucose‐induced electrical activity were studied in micro‐dissected mouse Islets of Langerhans. Both catecholamines induced hyperpolarization and blocked electrical activity in the presence of 11·1 mM glucose. Phentolamine, but not propranalol, blocked these effects, indicating predominantly α receptor action. Quinine, but not tetraethylammonium ions, antagonized the inhibitory effects of the catecholamines. The data are consistent with the hypothesis that α receptor activation induces a transient increase in intracellular Ca2+ concentration which in turn leads to an increase in K+ permeability.
GLUCAGON AND ALANINE‐INDUCED INCREASES OF THE CANINE RENAL GLOMERULAR FILTRATION RATE
Authors: Palmore William P.
Published: December 2014

Renal responses to intravenous DL‐alanine (ala) and glucagon (GLN) infusions were compared in conscious dogs. Doses of GLN (0·1 µg/min) that did not increase plasma glucose (PG) concentrations, a physiological effect of GLN, stimulated glomerular filtration rate (G.F.R.). Higher GLN infusion rates (1·0 and 10·0 µg/min) stimulated G.F.R., renal plasma flow (R.P.F.), PG, and potassium and urea clearances. Ala infusions (1·3 mmol/min) had similar effects if the dogs had been pre‐conditioned by feeding of corn starch, but not if they had been fed a normal diet. This level of ala infusion increased plasma a amino nitrogen to levels equivalent to plasma ala levels reported to stimulate GLN secretion. The reason for the lack of responsiveness to ala infusion when the normal diet was fed was not clear. When somatostatin (3·8, µg/min), an inhibitor of GLN secretion, and ala were infused simultaneously, G.F.R. was lower than when ala alone was infused. The data suggested that the ala‐induced renal effects were mediated by GLN.
THE EFFECT OF THE NUTRITIONAL STATE ON UTERINE PROSTAGLANDIN F METABOLITE CONCENTRATIONS IN THE PREGNANT EWE DURING LATE GESTATION
Authors: Fowden Abigail L. , Silver Marian
Published: December 2014

The effects of nutritional state and nutrient availability on arterial and uterine venous concentrations of 13, 14 dihydro‐15‐ketoprostaglandin F2α (PGFM) have been investigated in chronically catheterized pregnant ewes during late gestation (120‐144 d; term = 147 d). Before the daily feed of concentrates was given, a significant positive venous‐arterial (V-A) difference in plasma PGFM concentration was observed across the uterus, irrespective of the number of fetuses or the gestational age (mean value at 135 ± 2 d: 0·42 ± 0·06 ng/ml, n = 13, P 〈 0·01). However, by 3‐5 h after feeding, no significant difference in PGFM concentration could be detected across the uterus. Withdrawal of food but not water for 48 h increased the plasma PGFM levels and widened the V‐A difference in PGFM concentration across the uterus at all gestational ages studied but had the greatest effect in late gestation (〉 137 d). These changes in plasma PGFM were accompanied by a fall in glucose and a rise in free fatty acid (FFA) concentration in the arterial plasma. When these metabolite changes were reversed at the end of the fast either by refeeding or by glucose infusion, there was a rapid fall in PGFM concentration and a narrowing of the uterine V‐A difference. Induction of hypoglycaemia by infusion of insulin also led to a widening of the V‐A difference in PGFM concentration across the uterus. There was a significant inverse correlation between the arterial plasma glucose level and the V‐A difference in PGFM concentration across the uterus during feeding, fasting and insulin infusion. The V‐A difference in PGFM concentration was also positively correlated with the arterial plasma FFA level under these conditions. When arterial plasma concentrations of PGFM rose above 3 ng/ml, during fasting or insulin induced hypoglycaemia, the ewes lambed within 12‐24 h of restoring the metabolite concentrations. These observations indicate that the output of PGFM by the uterus is controlled in some way by the availability of nutrients and emphasize the importance of a regular food intake during late gestation in the ewes.
DISTRIBUTION OF TRANSFERRIN AND TRANSFERRIN RECEPTORS IN THE RABBIT PLACENTA
Authors: Baker Erica , van Bockxmeer F. M. , Morgan E. H.
Published: December 2014

The quantity and distribution of transferrin and transferrin‐binding sites in the placenta were investigated in rabbits on the 28th‐29th days of pregnancy. The animals were injected intravenously with a mixture of 59Fe‐125I‐labelled rabbit diferric transferrin and 131I‐labelled rabbit albumin. The binding of transferrin to placentas removed 3‐75 min later was determined by using the 131I‐labelled albumin values to correct for tissue content of plasma. Mean values for transferrin binding of 1460 and 560 µg/g tissue were obtained 3‐15 and 45‐75 min after injection, respectively. Gel filtration of placental extracts prepared with the non‐ionic detergent, Teric 12A9, showed that the 125I‐labelled transferrin bound to a large molecular weight component which had the properties of a specific receptor. The receptor had a higher affinity for differic transferrin than for apotransferrin. The subcellular distribution of transferrin binding sites was determined by differential centrifugation of placental homogenates and by electron microscope autoradiography. The results with the former method indicated that the transferrin was bound to the microsomal fraction of the cells. Autoradiography showed that the majority of the transferrin molecules were at intracellular sites, mainly on the membrane of intracellular vesicles. It is concluded that iron‐containing transferrin molecules enter the trophoblast cells by endocytosis or via a canalicular system after binding to cell membrane receptors. The higher affinity of the receptors for diferric transferrin than for apotransferrin explains the difference in amount of transferrin binding found within 15 min of injecting labelled diferric transferrin and that found 45‐75 min later when much of the iron had been removed from the transferrin.
CALCIUM‐EVOKED OPENING OF POTASSIUM CHANNELS IN HAMSTER EGGS
Authors: Georgiou P. , Bountra C. , Bland K. P. , House C. R.
Published: December 2014

Measurements of membrane potential and resistance have been made in zona‐free hamster eggs. The resting potential lay in the range −9 to −100 mV and the input resistance fell in the range 14 to 440 MΩ; high resting potentials were associated with large input resistances. Calcium injected ionophoretically into an egg from an intracellular micro‐electrode caused a reduction of the membrane resistance. The estimated reversal potential for the calcium‐evoked response was about −80 mV and its amplitude depended on the extracellular concentration of potassium but not on the chloride concentration. We conclude that membrane potassium channels open in response to a rise in the cytosolic concentration of calcium ions. Evidence is presented to suggest that micro‐electrode recordings of the membrane potential and resistance of eggs suffer from an impalement leak artifact. The presence of the artifact lowers the resting potential and resistance of the cell so that intracellular calcium injection causes a hyperpolarization. We conclude that a hyperpolarizing response to calcium would be unlikely in the absence of an impalement artifact.
LIGHT AND ELECTRON MICROSCOPY OF DORSAL SPINOCEREBELLAR TRACT NEURONES IN THE CAT: AN INTRACELLULAR HORSERADISH PEROXIDASE STUDY
Authors: Houchin Jane , Maxwell D. J. , Brown A. G. , Fyffe R. E. W.
Published: December 2014

Intracellular injections of horseradish peroxidase were made into dorsal spinocerebellar (d.s.c.t.) neurones in Clarke's column of the cat. All the d.s.c.t. neurones were excited from Group I muscle afferent fibres. The stained neurones were examined at the light and electron microscope level, and light microscope material was subjected to computer‐aided reconstruction and quantitative analysis. The dendritic trees of d.s.c.t. neurones extended about 3 mm in the long axis of the spinal cord and were confined, in the transverse plane, within or very close to Clarke's column. The dendrites branched extensively and carried various irregularities: complex clusters of fine branches, spine‐like protuberances and bead‐like varicosities. None of the axons of the cells showed any sign that they gave off collaterals. Computer‐aided reconstruction allowed the dendritic trees to be viewed from any angle and enabled measurements of their total dendritic lengths, surface area and volume. The dendritic diameters at branch points were tested against Rall's 3/2 power rule. Electron microscopical analysis confirmed and extended previous studies. Of particular significance was the observation that boutons containing flattened vesicles could be presynaptic to both a d.s.c.t. neurone and to a giant synaptic terminal that made contact with the same d.s.c.t. dendrite.
PERISTALSIS AND ANTIPERISTALSIS IN THE CHICKEN CAECUM ARE MYOGENIC
Authors: Hodgkiss J. P.
Published: December 2014

Peristalsis in the chicken caecum was investigated by recording the responses of isolated segments of the caecum to either fluid distension using a modified Trendelenburg apparatus or by monitoring circular muscle activity following localized radial distension of adjacent areas. Raising the intraluminal pressure did not initiate peristalsis except in the presence of tetrodotoxin, local anaesthetics and high concentrations of phentolamine. The effect of these drugs was reversible. Localized distension generally produced either a small relaxation of the circular muscle or no response at all on both sides of the site of distension. After exposure to tetrodotoxin one, or more (usually several), rhythmic propogating contractions were initiated at the point of distension. These results suggest that intrinsic inhibitory neurones are present in the caecum and may be triggered by distention. The possible role of these inhibitory neurones in the emptying and filling of the caecae is considered.
CYCLIC AMP AS A POSSIBLE MEDIATOR OF DOPAMINE STIMULATION OF COCKROACH GLAND CELLS
Authors: Gray D. C. , Ginsborg B. L. , House C. R.
Published: December 2014

Isolated salivary glands of the cockroach Nauphoeta cinerea Olivier secrete fluid in response to nerve stimulation or application of dopamine, the acinar cells undergoing a hyperpolarization during secretion. The aim of the present work was to examine whether cyclic AMP acts as a second messenger in the acinar cells to cause the secretory and electrical responses to the transmitter dopamine. Cyclic AMP (10–500 µM) in the bathing solution of isolated glands caused a dose‐dependent secretory response but no change in the membrane potential of acinar cells. The time courses and magnitudes of the secretory responses to cyclic AMP resembled those features of responses to dopamine. Forskolin, an adenylate cyclase activator, caused fluid secretion but the responses were small and irregular. The phosphodiesterase inhibitor, 3‐isobutyl‐1‐methylxanthine (IBMX) (1–1000 µM) produced fluid secretion in a dose‐dependent manner, the maximal response being equal to that of dopamine. Maintained responses to cyclic AMP or IBMX required the presence of extracellular calcium ions. An inhibitor (MDL 12,330A) of adenylate cyclase suppressed the secretory responses to dopamine, cyclic AMP,IBMX, the ionophore A23817 or the readmission of calcium ions to the bathing solution; this inhibitor did not block the acinar hyperpolarization caused by nerve stimulation. Cyclic AMP stimulation of glands, bathed in chloride‐free solution to prevent fluid secretion, produced a change in the gland cells which outlasted the period of exogenous cyclic AMP stimulation and expressed itself as a transient secretion upon return of the normal bathing solution. It was concluded that stimulus‐secretion coupling in this gland involves a calcium‐dependent second messenger system and that cyclic AMP is probably the second messenger. The evidence did not support the idea that cyclic AMP is also a second messenger for the acinar cell hyperpolarization evoked by nerve stimulation.
APPLICATION OF HIGH PERFORMANCE LIQUID CHROMATOGRAPHY TO STUDY TRANSPORT AND METABOLISM OF NUCLEIC ACID DERIVATIVES BY RAT JEJUNUM IN VITRO: ENDOGENOUS WASHOUT
Authors: Parsons D. S. , Shaw M. I.
Published: December 2014

Quarterly Journal of Experimental Physiology 68–1 (1983)

On page 40 paragraph 7 should read

Enzymes were purine nucleoside phosphorylase (PNP) (E.C. 2.4.2.1.), uricase (E.C. 1.7.3.3.), hexokinase (E.C. 2.7.1.1.), glucose‐6‐phosphate dehydrogenase (E.C.1.1.1.49.), alanine dehydrogenase (E.C.1.4.1.1.), glutamate dehydrogenase (E.C.1.4.1.3.) all from Boehringer, and xanthine oxidase (XOD) (E.C.1.3.2.) from Sigma.
THE DEPENDENCE OF EXOCRINE PANCREATIC SECRETION ON INSULIN IN SHEEP
Authors: Pierzynowski Stefan , Barej W.
Published: December 2014

Exocrine pancreatic secretion, blood insulin, glucose and free fatty acid concentrations were measured on days 1, 4 and 5 of a 5 d experimental period. Sheep were treated with alloxan (day 2) and insulin (day 5). The volume of pancreatic juice decreased markedly in the diabetic state and returned to the initial value after insulin treatment. The daily secretion of lipase and amylase decreased during development of diabetes. Injection of insulin restored the secretion of lipase but not amylase. It is suggested that insulin potentiates the stimulatory action of the vagus nerve on the pancreatic secretion of sheep.
A COMPARISON OF THE EFFECT OF BILE SALTS ON MAXIMAL HEPATIC EXCRETION OF CERTAIN ORGANIC ANIONS IN THE RABBIT UNDER URETHANE AND PENTOBARBITONE
Authors: Esteller A. , González J. , LÓpez M. A. , Hidalgo F.
Published: December 2014

The influence of two different anaesthetics, sodium pentobarbitone and ethyl urethane, on the enhancement of maximal bilirubin and bromosulphthalein (BSP) excretion induced by bile salts was investigated in rabbits. Two micelle‐forming (glycodeoxycholate and taurocholate) and one non‐micelle‐forming (dehydrocholate) bile salts were used. Under urethane anaesthesia the bile flow was lower than with pentobarbitone, and this could be attributed to a smaller bile salt non‐dependent fraction of secretion. The effect of bile salts on the maximal excretion of the two organic anions appeared more clearly related to some kind of micelle interaction in rabbits anaesthetized with urethane than in pentobarbitone‐anaesthetized animals. Thus, under urethane, infusions of glycodeoxycholate substantially increased the maximal excretion of bilirubin and BSP, taurocholate exerted an intermediate and dehydrocholate only a small effect. Under pentobarbitone, however, the augmenting action of all three bile salts was similar. The influence of bile salts on the endogenous excretion of bile pigments in experiments in which the test anion was BSP showed corresponding differences dependent upon the anaesthetic used. Possible explanations for those results are discussed.
CONDUCTION VELOCITY AND AXONAL DIAMETER OF ALIMENTARY C FIBRES
Authors: Cottrell David F.
Published: December 2014

Experiments were undertaken to investigate the numerical relationship between the axon diameter and conduction velocity (scaling factor) of non‐myelinated axons supplying the duodenum of the sheep and rabbit. Transmission electron microscopy and light microscopy of duodenal nerves showed distinct species differences. In the rabbit, all axons were non‐myelinated and three classes of nerves were found each containing axon populations with different diameters. Sheep nerves had a mixed population of non‐myelinated axons and contained 5% myelinated axons. There were significantly more Schwann cells containing single axons in sheep nerves than in rabbit nerves. The conduction velocities of functionally identified single afferent units in both species were measured during acute experiments in anaesthetized preparations. For pooled results of five C fibres taken over the temperature range 25–41 °C, a linear relationship between conduction velocity and temperature was found: c.v.% = 0·0114T+0·317 (c.v.% = ranked conduction velocity; T = temperature (°C)). At 39°C a scaling factor between 0·89 and 1·26 is required to convert non‐myelinated axon diameter to conduction velocity in duodenal nerves.
THE EFFECTS OF INTRAVENOUS PHOSPHATE LOADING ON SALIVARY PHOSPHORUS SECRETION, NET INTESTINAL PHOSPHORUS ABSORPTION AND PATHWAY OF EXCRETION IN SHEEP FED ROUGHAGE DIETS
Authors: Scott D. , McLean A. F. , Buchan W.
Published: December 2014

Mature sheep fitted with rumen and duodenal cannulae and fed either pelleted hay or grass diets were given supplementary phosphorus by continuous intravenous infusion and the effects on salivary phosphorus secretion, intestinal phosphorus absorption and pathway of excretion were studied. In control periods little phosphorus was excreted in the urine, the faeces being the major pathway for excretion. Infusion of phosphorus increased both urine and faecal phosphorus excretion though in sheep fed the hay diet the urine response was much less marked than in those fed the grass diet. This was not due to differences in plasma phosphate levels but rather to differences in renal tubular reabsorptive efficiency, though the reason for this is at present unclear. Intravenous phosphate loading had little effect on salivary phosphorus secretion, most of the increase in faecal phosphorus excretion being the result of reduced reabsorption within the intestine. The significance of these changes in relation to the control of phosphorus balance in ruminants is discussed.
INGESTION IN FETAL SHEEP AND ITS RELATION TO SLEEP STATES AND BREATHING MOVEMENTS
Authors: Harding R. , Sigger J. N. , Poore E. R. , Johnson P.
Published: December 2014

Swallowing was recorded electromyographically in unanaesthetized fetal sheep in utero during the last third of gestation. In control fetuses bouts of swallowing were, on average, 2·0 min in duration and occurred at intervals of 2·31 h. Swallowing bouts were associated with a low‐voltage electrocorticogram, eye movements and, in 82% of instances, with phasic activity in the dorsal neck muscles. These data indicate that fetuses are not in quiet (non‐rapid eye movement; n.r.e.m.) sleep when swallowing and also suggest that they are not in r.e.m. sleep as conventionally defined; we consider that fetuses may be in a state of heightened activity resembling wakefulness. Swallowing bouts were always accompanied by fetal breathing movements. When a swallow coincided with an inspiratory effort the diaphragm was briefly inhibited. Evidence was obtained that bouts of fetal ingestive activity were not dependent upon outpourings of fluid from the lungs and were not significantly influenced by volume information from the gastric compartments.
SODIUM CURRENTS IN SKELETAL MUSCLE FIBRES FROM THE TOAD BUFO MARINUS
Authors: Arispe N. J. , Argibay J. A. , Rojas L. V.
Published: December 2014

Single fibres from the sartorius muscle of the toad Bufo marinus were used to study ionic currents, using a fast voltage‐clamp method. Sodium currents were analysed following Hodgkin‐Huxley formulations. Internal caesium fluoride blocks delayed currents but produced shifts in the equilibrium potential of the early channel due to sodium accumulation. Delayed channels are very unstable when fluoride is used inside the fibre. These instabilities and equilibrium potential shifts were eliminated on replacing fluoride by aspartate in the internal solution. Late peaks of inward current, probably associated with activity at the tubular system, were occasionally observed for small depolarizations. The results are compared with those obtained for other amphibian species and used to explain more general electrophysiological properties of muscle fibres of this tropical toad.
THE LOCALIZATION OF GASTRIN‐LIKE IMMUNOREACTIVITY (GIR) IN THE ALIMENTARY TRACT OF THE SHEEP
Authors: Bunnett N. W.
Published: December 2014

Using an antiserum raised against synthetic cholecystokinin (CCK 8), the localization and distribution of gastrin‐like or CCK‐like immunoreactivity was investigated in the alimentary tract of the sheep by the method of indirect immunofluorscence. Immunoreactive cells were confined to the mucosa of the abomasal antrum and the proximal small intestine and were not observed in the oesophagus, rumen, reticulum, omasum, abomasal fundus, ileum, large intestine, pancreas or gall‐bladder. Antral tissue was fixed for electron microscopy and stained by the unlabelled antibody peroxidase anti‐peroxidase procedure. Stained cells were found across the entire thickness of the mucosa. Adjacent sections stained with heavy metals revealed secretory granules with an electron‐dense core and some G cells possessed a tuft of microvilli projecting into the glandular lumen.
MOUSE MUTANTS AS MODELS IN ENDOCRINE RESEARCH
Authors: Charlton H. M.
Published: December 2014

Although Shire (1979) has listed some forty‐eight mouse mutants of interest to the endocrinologist, this short review has concentrated upon eleven mutations which have resulted in a significant number of scientific publications over the last 4 or 5 years. The selection of references has had to be limited, but it should be possible easily to expand the list given in this review.

Although the proximate cause of none of the eleven mutations has been identified with certainty, the abnormalities of function have included hormone deficiencies and receptor and post‐receptor malfunctions.

It is perhaps a reflexion on our society in the 1980s, that the bulk of research has concentrated on the obese mouse. However, we still do not know the initial cause of this syndrome.

The major disadvantage of the mouse to the hormone assayist lies in the small blood volume and the extreme difficulty in taking serial blood samples over a short period of time. With increased sophistication of assay techniques this may prove less daunting, but is an area where a review of the literature reveals discrepancies between laboratories, and even between data generated by the same laboratory at different times. With regard to the hormone content of endocrine tissues, the way forward for peptide‐secreting glands may be in the measurement of mRNA levels for particular hormones. Certainly the methods of recombinant‐DNA technology will yield positive information upon the aetiology and expression of some of the syndromes considered above.

Organ transplantation is an area in which mutant mice have proved useful, for example gonadal, pituitary and pancreatic tissue transplantation. The grafting of neural tissue in the hpg mouse has added a further dimension to this field of research.

The great infrastructure of genetical research in mice has enabled us to breed mutant genes onto different genetic backgrounds. This area of research is one which deserves to expand. The techniues of in vitro fertilization, chimera formation and embryo transfer have been used, in part, in studies on mouse mutants, and should provide technical means for further investigating gene expression.

The family of dwarf mutants are ideally suited for research into the expression of genes micro‐injected into the fertilized egg (see Charlton & Cox, 1983).

As new hormones are isolated and become available for study these mouse mutants may well be useful in delineating physiological functions for natural and pharmacological products. Again, the dwarf mutants would seem ideally suited for research into the synthesis and action of GRF.

Mouse mutants have proved of use to biochemists and embryologists and provide fertile ground for endocrine investigations ranging from molecular genetics to membrane biophysics.
THE EFFECTS OF SHORT‐TERM VOLUNTARY IMMOBILIZATION ON THE CONTRACTILE PROPERTIES OF THE HUMAN TRICEPS SURAE
Authors: White M. J. , Davies C. T. M. , Brooksby P.
Published: December 2014

In four male subjects one leg was immobilized in a full leg cast for 2 weeks. Measurements of the contractile properties of both triceps surae were made before, during and after immobilization. There was a significant increase in the mean twitch time to peak tension (Tc) after 1 week of immobilization from 126 ± 10 ms to 143 ± 20 ms (P 〈 0·05) and in the half‐relaxation time (T½r) from 88 ± 7 ms to 107 ± 12 ms (P 〈 0·01). There were no further significant (P 〈 0·1) changes in the twitch characteristics during the second week of immobilization. The strength of a maximal voluntary contraction (m.v.c.) declined by 11% (P 〈 0·05) after 1 week and 24% (P 〈 0·05) after 2 weeks. Twitch tension, tetanic tension and muscle fatigability were not significantly altered during immobilization. Muscle (plus bone) calf cross‐sectional area (A) was reduced by 5% (P 〈 0·01) after 1 week and a further 3% (P 〈 0·05) after 2 weeks. The Tc and T½r of the twitch, m.v.c. and A returned to control values within 2, 7, 4 and 14 d respectively. No significant (P 〉 0·01) changes were observed in the mechanical properties of the triceps surae of the contralateral limb during the period of immobilization. The results suggest that short‐term voluntary immobilization is associated with atrophy and a diminished capacity of the muscle to develop maximal voluntary force. The increased contraction time of the twitch may indicate a change in the excitation‐contraction coupling mechanism of the muscle and the disproportionate decrease in m.v.c. in relation to A and tetanic tension a reduction in the central neural drive.
THE EFFECT OF MATERNAL WATER DEPRIVATION ON OVINE FETAL BLOOD VOLUME
Authors: Bell R. J. , Wintour E. M.
Published: December 2014

Fetal blood volume was measured in pregnant ewes bearing chronically cannulated fetuses in the last third of gestation. The increase in fetal blood volume secondary to growth was established from serial measurements in four control animals. The effect of maternal dehydration was assessed by measuring the change in fetal blood volume during twelve episodes of maternal water deprivation in another six ewes. Fetal blood volume increased during each episode of maternal dehydration. In five experiments the rate of increase was greater than controls and in seven experiments the rate of increase was less than controls. Thus, fetal hypovolaemia does not occur during maternal dehydration in the ovine fetus in the last third of gestation.
THE SOURCE AND DISTRIBUTION OF SHORT‐TERM SYNCHRONY BETWEEN γ‐MOTONEURONES IN THE CAT
Authors: Ellaway P. H. , Murthy K. S. K.
Published: December 2014

The naturally occurring background discharges of γ‐motoneurones to gastrocnemius and soleus in the decerebrated, spinal cat show a degree of short‐term synchrony which is absent when the spinal cord is intact. The characteristics of this synchrony and the mechanism producing it have been examined in the preceeding paper (Ellaway & Murthy, 1985). Short‐term synchrony in the background discharge is removed by cutting the ipsilateral dorsal root (S1 or L7) at the segment of origin of the γ‐efferents. It persists on cutting other ipsilateral or any contralateral dorsal roots between L6 and S3. The source is not the homonymous or synergist muscle group. Neither is the skin which lies around the insertion of gastrocnemius‐soleus on the heel the afferent source of this synchrony. However, stimulation of the heel by light stroking or pressure raises the frequency of γ‐efferent discharge and increases the degree of synchrony. Such stimulation does not produce synchrony in the decerebrated cat with an intact spinal cord. Synchrony between γ‐motoneurones is as strong between different fascicles of a muscle (gastrocnemius medialis), or different heads (gastrocnemius medialis and lateralis), as it is within one fascicle of a muscle. The timing of the peak incidence of correlated discharges always indicated synchrony at the level of the spinal cord irrespective of differences in peripheral conduction time or the destination of the axons. Hamstring and pretibial flexors show a lower incidence or weaker degree ofshort‐term synchrony between homonymous γ‐efferents compared with gastrocnemius. Short‐term synchrony is either weak or absent between γ‐motoneurones to heteronymous muscles. γ‐Efferents from homologous muscles on either side of the cord lack synchrony of discharge. The results go some way to establishing the source and connectivity to the motoneurone pool of afferents capable of synchronizing the discharge of γ‐efferents.
DRUG EFFECTS ON THE HYDRAULIC CONDUCTIVITY OF THE ISOLATED RABBIT CILIARY EPITHELIUM
Authors: Green Keith , Mayberry Linda
Published: December 2014

Three aspects of hydrostatically driven volume flow across the isolated rabbit ciliary epithelium have been examined. (1) Hydraulic conductivity was increased in a dose‐dependent manner by amiloride, but not by furosemide, indicating that amiloride may interfere with junctional permeability. The absence of a furosemide effect suggests that regulation of passive fluid movement may be independent of net ionic fluxes of either chloride or bicarbonate. Ethacrynic acid had no effect on hydraulic conductivity at concentrations below 10−2 M. At 10−2 M, hydraulic conductivity was decreased, suggesting that fluid pathways may be linked to ionic pathways. (2) Successive in vivo daily treatments with adrenergic agonists result in changes in the intraocular pressure response. Dose‐effect curves to in vitro agonists from eyes pre‐treated on successive days indicate that isoprenaline caused a lack of response in hydraulic conductivity after 3 d of in vivo treatment, adrenaline caused responses after 2 d which were about half of those found on day 0, while phenylephrine and noradrenaline had no influence on hydraulic conductivity. These data suggest that ,8‐agonists cause a deactivation or desensitization of some moiety which is coupled with regulation of hydraulic conductivity in a manner similar to that seen for the β‐receptor‐coupled adenylate cyclase. (3) While cyclic GMP was without effect, various modifiers of cyclic GMP activity increased hydraulic conductivity. Alteration of cellular cyclic GMP levels appears to exert some regulation over ciliary epithelial permeability.
CHANGES IN BLOOD FLOW DISTRIBUTION IN EQUINE LUNGS INDUCED BY ANAESTHESIA
Authors: Dobson A. , Gleed R. D. , Meyer R. E. , Stewart B. J.
Published: December 2014

The distribution of blood flow to the lungs was measured with labelled microspheres injected into horses before and during anaesthesia. Anaesthesia was induced with glycerol guaiacolate ether and ketamine, and maintained with the spontaneous breathing of halothane in oxygen. In a preliminary group of six horses, flow distribution was observed during anaesthesia in sternal, dorsal and right lateral recumbency. In two other groups, each of four horses, the flow distribution with time during either sternal or right lateral recumbency was observed. A small, constant proportion of the 15 µm diameter microspheres bypassed the lungs. No increase in shunting with anaesthesia was detected. Blood flow distributed predominantly cranioventrally in the conscious horse in concordance with the expected effects of hydrostatic forces within the lung. In the anaesthetized horse a stable distribution rapidly developed whereby the flow was directed preferentially caudodorsally and evenly divided between the left and right lungs regardless of whether the horse was on its back, side or sternum. We conclude that an unidentified factor overrides gravitational effects on perfusion in the anaesthetized horse. If under anaesthesia, ventilation were distributed according to gravity, hypoxia would arise from this disassociation of ventilation from perfusion. The hypoxia would be most intense in dorsal recumbency, and least intense in sternal recumbency. This was reflected in the degree of hypoxaemia observed. A small but significant change in flow distribution with the phase of the respiratory cycle was detected in the conscious, standing horsehorse.
ACTIONS AND INTERACTIONS OF GABA AND BENZODIAZEPINES IN THE MOUSE HIPPOCAMPAL SLICE
Authors: Biscoe T. J. , Duchen M. R.
Published: December 2014

Intracellular recordings have been made from CA1, CA3 and dentate cells of the mouse hippocampal slice. γ‐aminobutyric acid (GABA) and the water‐soluble benzodiazepines, midazolam and flurazepam were applied close to the impaled cell somata by microelectrophoresis. GABA always caused a fall in input resistance, although the associated changes in membrane potential were variable. These were consistent with reports which have defined a hyperpolarizing response to somatic and a depolarizing response to dendritic application of GABA to CA1 and CA3 cells in the rat and guinea‐pig. In this study, the phenomenon was seen in CA1, CA3 and dentate cells. The reversal potential for the hyperpolarizing, somatic response to GABA lay between ‐70 and ‐75 mV, similar to the reversal potential of the evoked recurrent inhibitory post‐synaptic potential (i.p.s.p.). The change in cell input conductance caused by GABA was larger at membrane potentials positive to the resting potential and smaller at hyperpolarized membrane potentials. Extracellular recordings of action potential frequency were made from ten cells in which the application of either midazolam or flurazepam increased the inhibitory potency of GABA. In three of these cells, the benzodiazepine reduced action potential frequency slightly when applied alone. Neither midazolam nor flurazepam had a consistent effect on membrane potential, resting input resistance or the current‐voltage (I‐V) relations of the cells when ejected alone. In twenty‐eight of forty‐one cells examined in detail, ejection of either midazolam or flurazepam was found to increase the response to GABA. In six cells, the response to GABA was significantly reduced by the benzodiazepine tested whilst in the remainder, no interaction of the drugs could be demonstrated. Examination of the dose‐ response relation for GABA alone and in the presence of was increased by the benzodiazepine in some cells while it midazolam or flurazepam showed that the maximal response to GABA was unchanged in others. When intracellular electrodes were filled with potassium chloride, spontaneous depolarizing GABA‐mediated post‐synaptic potentials (p.s.p.s) were seen. Measurement of the interval and amplitude distributions of these events showed that flurazepam increased their amplitude but not their frequency.
THE RESPONSE OF SLOWLY ADAPTING MECHANORECEPTORS IN THE CAT KNEE JOINT TO TETANIC CONTRACTION OF HIND LIMB MUSCLES
Authors: Ferrell W. R.
Published: December 2014

The effect of tetanic contraction of muscles acting at the cat knee joint on the discharge of various types of slowly adapting knee joint receptors was investigated. Contraction of a particular muscle could either increase, decrease or produce no alteration in the discharge of a given receptor. Whatever effects were produced by muscle contraction, these effects were always maximal at extremes of the flexion/extension range, and enhanced by limb movement. However, these receptors could not be induced to discharge at intermediate positions either by the passive tension or active contraction of muscles around the knee joint. It is concluded that muscle contraction does not increase the proportion of joint receptors (∼18%) which are known to spontaneously discharge at intermediate positions in the absence of significant muscle tone (Ferrell, 1980).
THE EFFECT OF Na+ AND Cl- REMOVAL AND OF LOOP DIURETICS ON ACETYLCHOLINE‐EVOKED MEMBRANE POTENTIAL CHANGES IN MOUSE LACRIMAL ACINAR CELLS
Authors: Suzuki Kazuo , Petersen Ole Holger
Published: December 2014

Intracellular micro‐electrode recordings were made from acinar units in mouse lacrimal gland segments superfused with physiological saline solutions. Two micro‐electrodes were used: one for recording the membrane potential and the other for current injection. A third extracellular micropipette was used for local ionophoretic acetylcholine (ACh) application. The ACh‐evoked membrane potential change was recorded at the spontaneous resting potential and after the resting potential had been increased or decreased by direct current injection. The membrane potential at which ACh did not evoke any change in potential (null potential, reversal potential) (EACh) was determined. EACh was about ‐53 mV under normal ionic conditions. When all Cl− in the superfusion fluid was replaced by NO3− or all Na+ replaced by N‐methyl‐D‐glucamine+ (NMDG+) or Tris+, EACh was shifted to more negative values. During exposure to Cl−‐free NO3− solution or Na+‐free NMDG+ solution EACh was about ‐72 mV. These effects on EACh were fully reversible. Inclusion of the loop diuretics piretanide (2 x 10−4 M) or furosemide (l0−3 M) also shifted EACh towards more negative values. In these cases EACh was the same as during exposure to Na+‐free Tris+ solution with a value of about ‐62 mV. Replacement of extracellular Cl− by Br− had no effect on EACh whereas replacement of Na+ by Li+ shifted EACh towards less negative values. The results can most easily be understood in terms of a cellular transport model in which Ca2+‐activated Cl− channels are present in the luminal membrane whereas the basolateral membrane contains three transport proteins: the Na+‐K+‐pump, the Na+‐K+‐2Cl− co‐transporter and the Ca2+‐activated K+ channel. These three transport proteins function together as a Cl− pump. ACh acts to open both Cl− and K+ channels via an increase in the free [Ca2+]i. When the Na+‐K+‐2Cl− co‐transporter is blocked by Na+ removal or by the loop diuretics, [Cl−]i drops and ECl (the Cl− equilibrium potential) becomes more negative. The permeability of the Cl− pathway may also decrease.
THE DEPENDENCE OF THE RELAXATION OF TENSION OF FROG ATRIAL TRABECULAE ON THE SODIUM‐CALCIUM EXCHANGE: A VOLTAGE‐CLAMP STUDY
Authors: Chapman R. A. , Rodrigo Glenn C.
Published: December 2014

The dependence of the relaxation of tension of isolated frog atrial trabeculae, upon membrane potential, [Na]o and [Ca]o, has been studied under voltage‐clamp conditions. The change in tension following the repolarization of the membrane potential can be resolved into two phases: an initial phase which opposes relaxation and has an exponential time constant of about 80 ms and is unaffected by changes in either membrane potential, [Na]o or [Ca]o; and a subsequent exponential fall in tension, the rate of which is slowed by depolarization, raised [Ca]o or lowered [Na]o. The dependence of the second phase of relaxation upon the membrane potential is consistent with Ca2+ being removed from the sarcoplasm by an Na‐Ca exchange in the cell membrane which has a coupling ratio close to 3 Na+ for each Ca2+. To explain the full effects of changes in [Na]o and [Ca]o upon relaxation with the same Na‐Ca exchange stoicheiometry it is necessary to assume that these changes in the bathing fluid affect [Na]i and that relaxation is dependent upon a single unbinding step, involving Ca2+ and the regulatory proteins.
INFLUENCE OF CARBON DIOXIDE TENSION IN THE CEPHALIC CIRCULATION ON HIND‐LIMB VASCULAR RESISTANCE IN ANAESTHETIZED DOGS
Authors: Soladoye A. O. , Rankin A. J. , Hainsworth R.
Published: December 2014

In dogs anaesthetized with chloralose, the effects were determined of changes in cephalic blood PCO2 on vascular resistance and on the reflex vascular responses to stimulation of baroreceptors and chemoreceptors. Both vagus nerves were cut above the nodose ganglia, both carotid sinus regions were perfused with blood at controlled pressures and the cephalic circulation was perfused with blood, equilibrated with various levels of CO2, through the brachiocephalic and left subclavian arteries. Increases in cephalic blood PCO2 between 4 and 6 kPa resulted in increases in arterial perfusion pressure in a vascularly isolated hind limb. These responses were inhibited at high carotid sinus pressures and the responses to changes in carotid pressure were enhanced at high levels of cephalic PCO2. The reflex increase in vascular resistance resulting from stimulation of carotid chemoreceptors, however, was unaffected by the level of cephalic blood CO2. These results indicate that the carbon dioxide tension in the cephalic circulation is of importance in the control of vascular resistance in the hind limb.
THE EFFECTS OF LONG‐TERM THRICE‐DAILY MILKING ON MILK SECRETION IN THE GOAT: EVIDENCE FOR MAMMARY GROWTH
Authors: Henderson A. J. , Blatchford D. R. , Peaker M.
Published: December 2014

Goats were milked twice daily for 2‐4 weeks after parturition. For the remaining 9 months of lactation, the right mammary gland was milked thrice daily while the left gland was milked twice daily. In the first and second weeks of thrice‐daily milking the milk yield of the right gland increased relative to the left gland. Subsequently there was only a slight increase in the difference in milk yields between the glands, which reached a maximum after 10 weeks. Total yield of the right gland for the period of thrice‐daily milking was significantly higher, by 30%, than that of the left gland. The peak yield of the right gland was significantly greater, by 29%, than that of the left gland. There was no significant difference between the rates of decline of yield ( persistency) from peak lactation. There were no significant differences in the composition of the milk from the two glands with respect to Na+, K+, Cl‐, lactose, protein, citrate, fat or calcium. At 40 weeks of lactation the weight of the right gland was significantly higher than that of the left gland and the weight of the parenchyma of the right gland was also significantly higher, by a similar percentage. At this stage of lactation, milk yield of the right gland was 43% higher than the left gland, while the weight of tissue was 34% higher. Thus over three‐quarters of the difference in yield was accounted for by the greater gland size, and the remainder by greater milk secretion per unit weight of tissue. The results are discussed in relation to the mechanisms responsible for the greater yield on long‐term, thrice‐daily milking. It is proposed that the extra milking led to growth of the mammary gland, facilitating the greater milk production.
MANNITOL PENETRATION OF LIVER CELLS IN ESTIMATIONS OF EXTRACELLULAR FLUID VOLUME
Authors: Glasby Michael A.
Published: December 2014

It has been suggested that since mannitol is excreted in the bile it may enter the liver cell and hence over‐estimate extracellular fluid volume if used as a marker. Boluses of D‐[14C]mannitol were injected into anaesthetized, nephrectomized dogs. After equilibration, liver biopsy samples were taken. Total liver water was estimated gravimetrically and compared with extracellular fluid volume estimated from the biopsy samples using beta‐counting. There was no significant difference between these two estimations. However D‐[14C]mannitol and [14C]inulin carboxylic acid spaces for liver were significantly different. This suggests that mannitol penetrates liver cells. A correction factor is derived to enable the technique to be used more accurately in ‘whole‐body’ extracellular fluid volume estimation.