Gentamicin dosage for the newborn.
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Gentamicins↗
Biomedical subjects
C Edwards
Publications and source records attributed to C Edwards.
The anion selectivity of the gamma-aminobutyric acid controlled chloride channel in the perfused spinal ganglion cell of frog.
The selectivity of the GABA-controlled Cl- channel in the membrane of the dorsal root ganglion cell of the frog has been measured in internally perfused cells by means of current and voltage clamp. When Cl- was replaced by various anions, the 10(-5) or 10(-4) M GABA-induced reversal potentials (EGABA) for Br-, I-, NO3-, ClO4-, SCN-, BF4- and ClO3- were more negative than that for Cl-, despite the fact that, in solution, the test anions are either larger than or similar in size to Cl-.
Animals↗
Induction of distinct types of spontaneous electrical activities in mammary epithelial cells by epidermal growth factor and insulin.
Electrophysiological measurements of the membrane potentials of mouse mammary epithelial cells in primary culture revealed the presence of spontaneous-oscillating-hyperpolarizing potentials in cells incubated with epidermal growth factor. The hyperpolarizing potentials were 5-20 mV in amplitude and about 10 sec in duration. The peak height of the response was reduced by hyperpolarization, and the input membrane resistance decreased during the response. The response was probably due to activation of K+ channels. The latency period for the epidermal growth factor induction of the hyperpolarizing potential was approximately 3 hr. In contrast, insulin induced spontaneous-depolarizing potentials that were about 5 mV in amplitude and 1 sec in duration. The depolarizing potentials were attributed to activity of ion channels, since the peak height was dependent on the membrane potential and the depolarizing potential was accompanied by a decrease of input membrane resistance. The time lag for the induction of the depolarizing potential was 6-12 hr. Other hormones involved in mammary cell differentiation, such as cortisol and prolactin, neither induced the depolarizing potentials nor changed the induction of depolarizing potential by insulin. In addition, other growth factors, such as nerve growth factor and fibroblast growth factor, elicited no electrical activity.
Animals↗
Meiosis can induce recombination in rad52 mutants of Saccharomyces cerevisiae.
The RAD52 and RAD50 genes have previously been shown to be required for normal meiotic recombination and for various types of recombination occurring in mitotic cells. Recent evidence suggests that rad52 mutants might be defective in an intermediate recombination step; we therefore examined recombination during meiosis in several rad52 mutants at several different loci and in genetic backgrounds that yield efficient sporulation and synchronous meiosis. Similar to previous reports, spores from rad52 diploids are inviable and meiotic recombination is greatly reduced by rad52 mutations. However, intragenic recombinants were detected when cells were plated on selective media during meiosis; rad52 mutants experience induction of recombination between homologues under these special conditions. The frequencies of recombination at four loci were considerably greater than the mitotic controls; however, they were still at least 20 times lower than corresponding Rad+ strains. The prototrophs induced by meiosis in rad52 mutants were not typical meiotic recombinants because incubation in nutrient-rich medium before plating to selective medium resulted in the complete loss of recombinants. We propose that previously observed single-strand breaks that accumulate in rad52 mutants may be associated with recombinational intermediates that are resolved when cells are returned to selective mitotic media and that the meiosis-induced recombination in rad52 cells does not involve double-strand breaks.
DNA Transposable Elements↗
Endemic Burkitt's lymphoma: phenotypic analysis of tumor biopsy cells and of derived tumor cell lines.
Tumor cells from 10 patients with Epstein-Barr virus-positive endemic Burkitt's lymphoma (BL) have been examined for cell surface phenotype, both at the biopsy stage and during BL cell line outgrowth in vitro, the cultures being followed for up to 150 passages. In all 10 cases, the biopsy cells showed coexpression of the common acute lymphoblastic leukemia antigen (CALLA) and of the BL-associated glycolipid antigen (BLA) with no accompanying expression of several "lymphoblastoid" cell surface markers defined by selected monoclonal antibodies. During cell line establishment and in vitro passage, the individual BL cell lines showed different degrees of progression toward a more "lymphoblastoid" cell surface phenotype, some even losing CALLA and BLA expression while retaining the chromosomal translocations indicative of their malignant origin. This differential capacity for phenotypic progression in vitro explains much, if not all, of the heterogeneity of the BL cell phenotype apparent from many previous studies with panels of long-established lines. Such heterogeneity in vitro belies the true homogeneity of the tumor cell phenotype in vivo.
Antibodies, Monoclonal↗
Effect of two new antisecretory drugs on fluid and electrolyte transport in a patient with secretory diarrhoea.
The effect of oral lidamidine hydrochloride and subcutaneous long acting somatostatin analogue, SMS 201-995, on stool output and salt and water transport in the small intestine was investigated in a patient with gross secretory diarrhoea caused by a vasoactive intestinal polypeptide (VIP) secreting tumour in the liver. Transport in the jejunum and ileum were assessed by steady state perfusion techniques. Under basal conditions, the patient was absorbing fluid and electrolytes from the jejunum and ileum, but at rates that were abnormally low. Lidamidine had no effect on either intestinal transport or stool frequency and output. SMS 201-995 increased intestinal absorption in the jejunum and ileum, reduced plasma VIP concentrations, daily stool frequency and weight, and enabled the patient to resume a normal diet without oral or intravenous fluid and electrolyte supplements. After two months of treatment, medical control was becoming increasingly difficult and stool output had risen again to 2 litres per day. Surgical resection, fortunately, was possible and led to resolution of symptoms and normal plasma VIP concentrations.
Adult↗
Poorly differentiated squamous carcinoma of the bronchus: a light and electron microscopic study.
As there is little published information on the ultrastructure of poorly differentiated squamous carcinoma of the bronchus 18 examples of this tumour were studied. On light microscopy 10 of the tumours contained foci of keratinisation or intercellular bridges and therefore fulfilled the World Health Organisation's diagnostic criteria. In eight these features were absent, but the overall appearance was sufficiently squamoid to preclude their placement in any other category. On electron microscopy many cells showed the characteristic desmosomes and tonofilament of of squamous carcinoma, but there were also areas of adenodifferentiation. The ultrastructure of both light microscopic groups was identical. In conclusion, this type of tumour is dimorphic with characteristics of adenocarcinoma and squamous carcinoma on electron microscopy. Keratinisation and bridges are not essential diagnostic criteria: the overall pattern and cellular morphology are more important.
Adenocarcinoma↗
Scar adenocarcinoma of the lung: a light and electron microscopic study.
Five well differentiated peripheral adenocarcinomas of the lung were investigated, using light and electron microscopy. Each tumour contained a central nidus of fibrous tissue and fulfilled the criteria for "scar cancer." One tumour also had a focus of lamellated collagenous tissue, suggestive of an old tuberculous granuloma. Electron microscopy showed the features of Clara cells, with characteristic dense bodies in the apical cytoplasm and scattered microvilli on the luminal surface. It was concluded that this variant of scar cancer was a carcinoma of Clara cells, which was sufficiently distinctive in appearance to be recognised on light microscopy alone. It remains uncertain, however, whether the central fibrous area is a desmoplastic response to tumour growth or a pre-existing scar.
Adenocarcinoma↗
Thiamine blockade of neuromuscular transmission.
The effects of thiamine on neuromuscular transmission were studied. Thiamine (0.2-2 mM) decreased the quantal height (q) of the evoked end-plate current (EPC). In the presence of 2 mM thiamine, the shape of the decay phase of the EPC remained exponential but the decay time constant increased dramatically. Thiamine changed the EPC height/holding potential and log (EPC decay time constant)/holding potential relationships from linear to non-linear. The reversal potential and the rate of rise of the EPC were unaffected. Analysis of the ACh-induced noise revealed that thiamine increased the mean channel lifetime and decreased the single channel conductance. Under normal conditions, the ACh-induced single channel conductance had no membrane voltage dependency, while thiamine caused the single channel conductance to decrease with hyperpolarization. The effects of thiamine could be explained in computer simulation of the peak EPC/membrane potential relationship by the assumption that thiamine prolonged the channel lifetime and decreased the single channel conductance with hyperpolarization. It is concluded that thiamine modifies the kinetics of ACh-receptor ion channel complex and that this effect is dependent on the membrane voltage.
Animals↗
Measurement of the decay Upsilon (2S)--> pi pi Upsilon (1S).
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Journal Article↗
Dietary sodium and arterial blood pressure: evidence against genetic susceptibility.
Thirty five subjects with both parents in the top third of their age specific blood pressure distributions and 31 subjects with both parents in the bottom third of their blood pressure distributions restricted their intake of sodium for eight weeks while taking part in a double blind, randomised crossover trial of supplements of sodium and placebo. A comparison of two periods of four weeks at different intakes of sodium showed no differences in blood pressure in either the groups as a whole or the subgroups who complied best with the diet and tablets. In the compliant subgroups mean urinary sodium excretions were above 120 mmol(mEq) and below 50 mmol/day. The study provides evidence against the hypothesis that people with a family history of high blood pressure are more susceptible in their blood pressure response to dietary sodium.
Adult↗
Effects of guanethidine and phenethylguanidine on the frog neuromuscular junction.
The effects of two guanidine derivatives, guanethidine and phenethylguanidine (2-phenyl-ethyl-guanidine), on neuromuscular transmission in the sartorius nerve-muscle preparation of the frog, Rana pipiens, were investigated. Both compounds decreased the peak height of the evoked end-plate current (EPC). The decay of the EPC was changed from a single exponential to a double exponential. The effects of both compounds on the EPC peak height increased with hyperpolarization, and the peak EPC/membrane voltage relationship thus became non-linear. The absence of an effect on the mean quantal content (m) indicated that the two compounds acted postsynaptically. The power spectrum of the ACh-induced noise was changed by guanethidine from a single Lorentzian to a double Lorentzian curve. The single channel conductance was decreased with hyperpolarization. It was concluded from these observations that guanethidine is an open channel blocker. Phenethylguanidine shifted the cut-off frequency of the ACh-induced noise to a higher frequency. However, the power spectrum showed only a single Lorentzian, and there was a lack of low frequency component in the power spectrum, which was expected from the decay phase of the EPC. The single channel conductance decreased, but in contrast to the case of guanethidine, there was no voltage dependency. The possible mechanism of action of phenethylguanidine is discussed.
Acetylcholine↗
Effects of hycanthone on the neuromuscular transmission.
The effects of the antischistosomal drug, hycanthone, on the synaptic transmission at the frog neuromuscular junction were studied. The mean quantal content increased in the presence of 20 microM hycanthone. The amplitude of the miniature end-plate current was unaffected by 20 microM hycanthone, while 2 microM hycanthone decreased the ionophoretic ACh response (ACh induced current). The decay time constants of the evoked end-plate current and the miniature end-plate current were increased with 1-5 microM hycanthone, but were decreased at concentrations over 20 microM. Analysis of the ACh induced noise revealed that 1 microM hycanthone slightly increased the channel lifetime whereas the single channel conductance was not affected. It was concluded that the primary site of action of hycanthone is the 'transient state' or ACh bound but closed conformation of the ACh receptor ion channel, but this drug also has other sites of action (presynaptic nerve terminal and open conformation of ACh receptor-ion channel complex).
Animals↗
Observation of three P states in the radiative decay of Upsilon (2S).
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Journal Article↗
Studies of innervation patterns in grafted chick wings.
The pattern of innervation of 12 day embryonic chick wings was studied by morphological and electrophysiological techniques. Several types of chick wing grafts were performed to investigate the rules governing nerve pattern formation: whether the motor neurons actively seek out and connect with specific muscles or are passively guided and whether cell death plays any role in pattern formation. In each type of graft the outgrowing neurons were confronted with extra targets distal to the elbow. Two grafts replicated lower arm parts in series (proximodistal graft) or in parallel (forearm and hand replicated in the same pattern of asymmetry in a split limb graft); a third produced a mirror image limb. The flexor carpi ulnaris muscle (F.C.U.) was studied in these limbs. The innervation of the most distal f.c.u. muscle in proximodistal grafted limbs varied with the extent of host f.c.u. muscle present. The f.c.u. muscles in the split limb graft were always innervated. In both limb grafts the f.c.u. muscles were innervated by the appropriate neurons, as determined by retrograde HRP technique and electrophysiological recordings. This strongly suggests that the motor neurons are able to seek out and connect with their appropriate muscle. Results of the mirror image limb graft suggest that other factors may be involved. In addition, motor neuron cell counts were performed. From this one can infer that the normally occurring pattern of cell death was not affected by the grafts. Cell death is therefore excluded as a major factor in nerve pattern formation.
Animals↗
Differential effects of acute DA receptor blockade with domperidone on LH and TSH release in patients with hyperprolactinemia.
Since dopamine (DA) has been implicated in the inhibitory control of both TSH and LH, we have compared TSH and LH levels following dopamine (DA) receptor blockade with domperidone in patients with hyperprolactinemia due to presumed prolactinomas. Eight euthyroid patients (aged 19-37 yr) with presumed prolactinomas each received domperidone (10 mg iv) at 11:00 and 23:00 h and tests were separated by at least one week. Basal TSH levels were significantly greater at 23:00 than at 11:00 h (2.7 +/- 0.5 vs 1.7 +/- 0.4 mU/l, mean +/- SE, p less than 0.01) whereas basal LH levels did not differ. All subjects showed clear rises in basal TSH levels following drug administration and these were significantly greater at 23:00 than at 11:00 h (p less than 0.02 at each time point). In contrast there was no alteration in LH levels following drug administration at either time of day. These data suggest that the mechanisms underlying the dopaminergic control of TSH and LH are different in these patients. Furthermore the data argue against an anterior pituitary or median eminence site of action of DA in the inhibition of LH release in hyperprolactinemia since domperidone does not penetrate the blood brain barrier to any appreciable extent.
Adult↗
The effects of cognitive task demand on subjective stress and blood glucose levels in diabetics and non-diabetics.
Blood glucose levels (BGLs) and subjective estimate of stress levels (SESLs) were measured repeatedly in 45 min baseline sessions on three successive days in insulin-dependent diabetic and non-diabetic groups. In the diabetic groups the initial level of BG was twice that of the non-diabetic group and BGLs declined steadily within each session but not across sessions whereas BGLs in the non-diabetic group remained steady both within and across sessions. On two subsequent days half of each group performed a high demand and half a low demand task, BGLs and SESLs being assessed before, during and after the stress period. Stress did not appear to induce significant changes in BGL in any of the groups even though SESL measures indicated that the task appeared stressful to the groups. The implications of these findings for the relationship between stress and increases or decreases in BGL are discussed.
Adult↗
Is an acetylcholine transport system responsible for nonquantal release of acetylcholine at the rodent myoneural junction?
Experiments were performed to investigate the effects on the spontaneous, nonquantal release of acetylcholine (AcCho) from motor nerve terminals of substances known to inhibit the AcCho transport system present in cholinergic synaptic vesicles. In mouse diaphragms, the hyperpolarization normally produced by d-tubocurarine in the endplate area of muscle fibers that had been treated by an anticholinesterase was partly or completely blocked by 2-(4-phenylpiperidino)cyclohexanol (AH5183, 0.1-1 microM), quinacrine (0.1 microM), and tetraphenylborate (1 microM). Since the sensitivity of the subsynaptic area to AcCho was not changed, the block of the hyperpolarizing action of d-tubocurarine indicated in inhibition of the spontaneous, nonquantal release of AcCho. This was confirmed in experiments on rat diaphragm using direct radioenzymatic measurement of the AcCho released into the incubation medium. The release of AcCho from the innervated diaphragm was decreased by about 50% in the presence of AH5183 (0.01-1 microM) and by 42% in the presence of quinacrine (0.1-1 microM). The AcCho released was presumably neural, since the release of AcCho from 4-day denervated diaphragms was not diminished by either AH5183 or quinacrine. The results indicate that the spontaneous release of AcCho from the motor nerve terminals is highly sensitive to low concentrations of specific inhibitors and is probably mediated by a carrier. It is proposed that spontaneous release is due to the incorporation into the membrane of the nerve terminal during exocytosis of the vesicular transport system responsible for moving AcCho into the vesicle.
Acetylcholine↗