Gradual hearing loss with bilateral labyrinthine hemorrhage in chronic myelogenous leukemia.
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Cochlea↗
Biomedical subjects
N Nelson
Publications and source records attributed to N Nelson.
Saliva collection using cotton buds with wooden sticks: a note of caution.
The aims of the present study were to investigate whether the cotton-tipped applicators (cotton buds) used to collect saliva in infants can be stored un-centrifuged prior to cortisol analysis, and to test whether there is any difference in results between wooden and plastic-shafted sticks. Saliva was collected from 10 healthy adults using 6 cotton buds, i.e. 3 with wooden sticks and 3 with plastic sticks. The samples were then centrifuged at three different time-points: immediately after collection, after 24 h and after 48 h. Using cotton buds with wooden sticks, median salivary cortisol was significantly lower after 24 h (40 %) (p<0.001) and after 48 h (49 %) (p<0.001) of storage than it was of the samples centrifuged immediately. There was no significant difference between the samples centrifuged immediately and those centrifuged after 24 h and 48 h when saliva was collected using the cotton buds with plastic sticks. It is concluded that cotton buds with wooden sticks should not be used in studies of salivary cortisol unless it is possible to centrifuge the saliva immediately. Moreover, it is inadvisable to alternate between cotton buds with wooden and plastic sticks in the same study when collecting saliva for analysis of cortisol.
Adult↗
Novel properties of a mouse gamma-aminobutyric acid transporter (GAT4).
We expressed the mouse gamma-aminobutyric acid (GABA) transporter GAT4 (homologous to rat/ human GAT-3) in Xenopus laevis oocytes and examined its functional and pharmacological properties by using electrophysiological and tracer uptake methods. In the coupled mode of transport (Na+/ Cl-/GABA cotransport), there was tight coupling between charge flux and GABA flux across the plasma membrane (2 charges/GABA). Transport was highly temperature-dependent with a temperature coefficient (Q10) of 4.3. The GAT4 turnover rate (1.5 s(-l); -50 mV, 21 degrees C) and temperature dependence suggest physiological turnover rates of 15-20 s(-1). No uncoupled current was observed in the presence of Na+. In the absence of external Na+, GAT4 exhibited two distinct uncoupled currents. (i) A Cl- leak current (ICl(leak)) was observed when Na+ was replaced with choline or tetraethylammonium. The reversal potential of (ICl(leak)) followed the Cl- Nernst potential. (ii) A Li+ leak current (ILi(leak)) was observed when Na+ was replaced with Li+. Both leak currents were inhibited by Na+, and both were temperature-independent (Q10 approximately 1). The two leak modes appeared not to coexist, as Li+ inhibited (ICl(leak)). The results suggest the existence of cation- and anion-selective channel-like pathways in GAT4. Flufenamic acid inhibited GAT4 Na+/Cl-/GABA cotransport, ILi(leak), and ICl(leak), (Ki approximately 30 microM), and the voltage-induced presteady-state charge movements (Ki approximately 440 microM). Flufenamic acid exhibited little or no selectivity for GAT1, GAT2, or GAT3. Sodium and GABA concentration jicroumps revealed that slow Na+ binding to the transporter is followed by rapid GABA-induced translocation of the ligands across the plasma membrane. Thus, Na+ binding and associated conformational changes constitute the rate-limiting steps in the transport cycle.
Animals↗
Propionate precursors and other metabolic intermediates as possible alternative electron acceptors to methanogenesis in ruminal fermentation in vitro.
Fifteen potential precursors of propionate were tested for their ability to decrease CH4 production by ruminal fluid in vitro. Sodium acrylate and sodium fumarate produced the most consistent effects in batch cultures, with 50 % of the added precursors being fermented to propionate and CH4 production decreasing by between 8 and 17 %, respectively. Additives were more effective when added as free acids, but this also decreased the pH and may have inhibited fibre digestion. Changing the dietary substrate from predominantly grass hay to predominantly concentrate had no influence on the effectiveness of acrylate and fumarate. In an in vitro fermentor (the rumen simulating technique, Rusitec) with a grass hay-concentrate (50:50, w/w) diet as substrate, both compounds were again fermented to propionate (33 and 44 % conversion to propionate, respectively). However, fumarate appeared more effective as a H2 sink compound. It was calculated to capture 44 % of the H2 previously used for CH4 formation compared with a 22 % capture of H2 with acrylate. Fumarate also caused a stimulation in fibre digestion. Thus, sodium fumarate was the preferred propionate precursor for use as a feed ingredient to decrease CH4 emissions from ruminants.
Acids↗
Asparaginase inhibition of adhesion of type 1-fimbriated and P-fimbriated Escherichia coli to epithelial cell receptors.
The 3D structures of Fim H and PapG proteins complexed with the host carbohydrate receptor demonstrate that both utilize binding-pocket asparagines for contact or stabilization with the carbohydrate. Pretreatment of whole bacteria with asparaginase resulted in decreased fimbriae-mediated attachment to urinary epithelial cells. Enzyme treatment of bacteria pre-adhered to epithelial cells removed more uropathogenic E. coli than the indigenous flora attached to them.
Asparaginase↗
Salivary cortisol and administration of concentrated oral glucose in newborn infants: improved detection limit and smaller sample volumes without glucose interference.
Newborn infants are subject to repetitive painful and stressful events during neonatal intensive care. When the baby attempts to cope with a stressful situation the hypothalamus-pituitary-adrenal axis is activated, releasing cortisol. The free cortisol response is optimally measured in saliva and saliva samples can be taken easily and without pain. However, saliva is very scarce in infants and saliva stimulants can interfere with analytical methods. Nowadays, sweet solutions are frequently administered to neonates prior to a disturbing procedure in order to reduce pain. The possible interference of sweet solutions with the measurement of salivary cortisol has not yet been documented. The aims of the present study were to further improve the detection limit of the radioimmunoassay used for cortisol analysis and to determine the degree of interference of high concentrations of glucose with the analytical method. By decreasing incubation temperature and prolonging the incubation time it was possible to improve the detection limit of the radio immunoassay (RIA) to 0.5 nmol/L at the same time as the sample volume was decreased to 10 microL saliva. Saliva was collected from full-term and preterm babies and was sufficient for analysis in 113 out of 116 (97%) samples. Glucose in the concentrations and amounts commonly used for pain relief did not interfere with the RIA method. In conclusion, it is feasible to collect microlitre volumes of saliva and analyse even very low concentrations of cortisol in newborns. It is also possible to offer the baby oral glucose prior to a painful procedure and still reliably measure salivary cortisol.
Administration, Oral↗
Clinical features of nasopharyngeal carcinoma in Jamaica.
Nasopharyngeal carcinoma is endemic in China, Hong Kong, and the Philippines. However, this disease is rare in North America and the Caribbean. This paper discusses the clinical features, prognosis, treatment outcomes, and survival rates of nasopharyngeal carcinoma in Jamaica. The incidence in Jamaica is 1.4 per 100,000. The National Cancer Registry in Jamaica keeps a record of all cancers. A retrospective cohort study of patients with nasopharyngeal carcinoma between 1988-2000 was reviewed. The presenting features, staging, histological diagnosis, treatment, and patient outcome were assessed. All patients received radiation therapy, and 89% of the patients completed the course of therapy. Seventeen percent received chemotherapy, consisting of cisplatin and 5-fluorouracil. Surgery played a minor role in the definitive management of nasopharyngeal carcinoma in this study. Three-year survival rates were 21%. The study demonstrates findings unique to the Caribbean nation of Jamaica. There is a bimodal pattern to the age distribution typical in non-endemic areas, such as shown in this study. Nasopharyngeal carcinoma evades early diagnosis because of its anatomic location and varied symptomatology. Prognostic indicators include intracranial extension, cervical node, and distant metastasis.
Adolescent↗
Evaluation of screening procedures for congenital cataracts.
AIM: To evaluate the efficacy of two different Swedish screening procedures for early detection of congenital cataracts in comparison with no screening. METHODS: Children born between January 1992 and December 1998 in Swedish regions with an established eye-screening routine procedure, diagnosed with congenital cataract, and operated on before 1 y of age, were included in a retrospective study. Age at referral and age at time of the operation were compared between regions using different screening procedures: screening in the maternity wards (Region 1), at the well-baby clinics (Region 2) and one region without any screening (Region 3). RESULTS: Seventy-two children were included in the study. Concerning early diagnosis and surgery, Region 1 differed significantly from Regions 2 and 3, which were more similar and were combined for further analysis. The difference in detected cases was greatest at 21 d of age (55% vs 18%; p < 0.001), but persisted even at 100 d of age (78% vs 64%; p < 0.02). Region 1 screening resulted in more and earlier cases detected than the other two regions (22 vs 15 per 100,000 births). In 72% of all cases, surgery was performed in response to referrals from either the maternity wards (36%), or the well-baby clinics (36%). However, half of the cases from the well-baby clinics were detected too late, i.e. at > 100 d. CONCLUSION: Eye screening in the maternity ward is preferable to well-baby clinic screening and to no screening at all, since it leads to early detection. Screening should also be performed routinely at well-baby clinics within the period when successful treatment is possible.
Cataract↗
Presteady-state and steady-state kinetics and turnover rate of the mouse gamma-aminobutyric acid transporter (mGAT3).
We expressed mouse gamma-aminobutyric acid (GABA) transporter (mGAT3) in Xenopus laevis oocytes and examined its steady-state and presteady-state kinetics and turnover rate by using tracer flux and electrophysiological methods. In oocytes expressing mGAT3, GABA evoked a Na+-dependent and Cl(-)-facilitated inward current. The dependence on Na+ was absolute, whereas that for Cl(-) was not. At a membrane potential of -50 mV, the half-maximal concentrations for Na+, Cl(-), and GABA were 14 mM, 5 mM, and 3 microM. The Hill coefficient for GABA activation and Cl(-) enhancement of the inward current was 1, and that for Na+ activation was > or =2. The GABA-evoked inward current was directly proportional to GABA influx (2.2 +/- 0.1 charges/GABA) into cells, indicating that under these conditions, there is tight ion/GABA coupling in the transport cycle. In response to step changes in the membrane voltage and in the absence of GABA, mGAT3 exhibited presteady-state current transients (charge movements). The charge-voltage (Q-V) relation was fitted with a single Boltzmann function. The voltage at half-maximal charge (V(0.5)) was +25 mV, and the effective valence of the moveable charge (zdelta) was 1.6. In contrast to the ON transients, which relaxed with a time constant of < or =30 msec, the OFF transients had a time constant of 1.1 sec. Reduction in external Na+ ([Na+]o) and Cl(-) ([Cl(-)]o) concentrations shifted the Q-V relationship to negative membrane potentials. At zero [Na+]o (106 mM Cl(-)), no mGAT3-mediated transients were observed, and at zero [Cl(-)]o (100 mM Na+), the charge movements decreased to approximately 30% of the maximal charge (Q(max)). GABA led to the elimination of charge movements. The half-maximal concentrations for Na+ activation, Cl(-) enhancement, and GABA elimination of the charge movements were 48 mM, 19 mM, and 5 mM, respectively. Q(max) and I(max) obtained in the same cells yielded the mGAT3 turnover rate, 1.7 sec(-1) at -50 mV. The low turnover rate of mGAT3 may be due to the slow return of the empty transporter from the internal to the external membrane surface.
Animals↗
DR3 is associated with type 1 diabetes and blood group ABO incompatibility.
Type 1 diabetes is associated with autoimmunity against pancreatic beta cells. ABO incompatibility is associated with ABO immunization during pregnancy. Type 1 diabetes is associated with certain HLA DR and DQ haplotypes. The mechanism by which blood group incompatibility is associated with the risk of type 1 diabetes is not known. We propose that certain HLA alleles contribute to the development of both type 1 diabetes and ABO blood group incompatibility. We studied 57 children with ABO blood group incompatibility, 118 children with type 1 diabetes, and 98 age- and sex-matched unrelated healthy controls from Linköping. Typing of HLA DQA1, DQB1, and DRB1 was done on DNA extracted from peripheral blood, by PCR amplification, manual dot-blotting onto nylon membranes, synthetic sequence-specific oligonucleotide (SSO) probe 3' end-labeling with 32P-dCTP, and hybridization followed by stringency washes and autoradiography. We observed that DR3 allele was more frequent in patients with ABO incompatibility when compared to healthy controls (OR = 2.7, P(c) < 0.05). Patients with type 1 diabetes had significantly higher frequency of DR3, DQ2, DR4, and DQ8 alleles when compared to healthy controls. No significant difference was observed in frequency of DR3 between ABO blood group incompatibility and type 1 diabetes patients. We conclude that DR3 is associated with both the development of type 1 diabetes and ABO incompatibility.
ABO Blood-Group System↗
Features of V-ATPases that distinguish them from F-ATPases.
The general structure of F- and V-ATPases is quite similar and they may share a common mechanism of action that involves mechanochemical energy transduction. Both holoenzymes are composed of catalytic sectors, F1 and V1 respectively, and membrane sectors, F(o) and V(o) respectively. Although we assume that a similar mechanism underlies ATP-dependent proton pumping by F- and V-ATPases in eukaryotic cells, the latter cannot catalyze pmf-driven ATP synthesis. The loss of this ability is probably due to a proton slip that is a consequence of alterations in its membrane sector. The major events include gene duplication of the proteolipids and the presence of three distinct proteolipids in each complex.
Adenosine Triphosphate↗
Recent studies show cell phone use is not associated with increased cancer risk.
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Brain Neoplasms↗
Beat-to-beat changes in stroke volume precede the general circulatory effects of mechanical ventilation: a case report.
BACKGROUND: The haemodynamic as well as the ventilatory consequences of mechanical ventilation can be harmful in critically ill neonates. Newly developed ventilatory lung protective strategies are not always available immediately and in an acute situation the haemodynamic changes caused by mechanical ventilation can affect the oxygen delivery considerably. We report the case of a male neonate who was treated with conventional pressure-controlled mechanical ventilation because of respiratory distress and progressive respiratory acidosis resulting from meconium aspiration. Because of poor arterial oxygenation despite 100% inspired oxygen and increased ventilator settings, echocardiography was performed to exclude central haemodynamic reasons for low oxygen delivery. METHOD: Doppler echocardiography was used for the measurement of stroke volume and cardiac output. Pulse oximetry and aortic blood pressure were monitored continuously. RESULTS: Echocardiography revealed no cardiac malformations or signs of persistent fetal circulation. When inspiratory pressures and duration were increased, beat-to-beat variation in stroke volume preceded decay in cardiac output. Stroke volume variations and oxygen saturation values guided ventilator settings until extracorporal membrane oxygenation could be arranged for. After recovery and discharge 4 weeks later the boy is progressing normally. CONCLUSION: Because oxygen delivery is dependent on both blood flow and arterial oxygen content, measurement of cardiac output as well as left heart oxygen saturation is a useful guide to optimizing oxygen delivery. This case report demonstrates how Doppler echocardiographic monitoring of beat-to-beat changes in stroke volume can be used to detect early negative haemodynamic effects of increased mechanical ventilation settings before cardiac output is affected.
Cardiac Output↗
Wheelchair use by patients with amyotrophic lateral sclerosis: a survey of user characteristics and selection preferences.
OBJECTIVES: To determine wheelchair types and features that are most beneficial to patients with amyotrophic lateral sclerosis (ALS), to ascertain at what stage of disease and disability patients benefit from wheelchair use, and to pinpoint the differences in patient characteristics between the users of manual and motorized wheelchairs. DESIGN: Internally generated questionnaire. SETTING: A neuromuscular clinic. PATIENTS: Forty-two patients (28 men, 14 women) with ALS who used wheelchairs and whose mean age was 53.9 years (range, 32-75yr). MAIN OUTCOME MEASURE: Wheelchair users completed a 39-item survey. RESULTS: At the time of the survey, the patients' mean Appel ALS rating scale total score was 84.5 (range, 48-138), indicating moderate disability. Forty-one patients reported that wheelchairs permitted them greater interaction in their communities; 33 were "very satisfied" with the positive impact of wheelchair use on their activity levels. Most users did not work and needed caregiver assistance for activities of daily living. The most desirable wheelchair features provide extra comfort (supports for the head, neck, trunk, extremities) and have improved maneuverability (lightweight frame, smaller wheelbase). Undesirable features are low sling backs and sling seats, nonremovable static leg rests, and large frames. No significant differences were reported between manual wheelchair users and motorized wheelchair users in terms of overall disease symptom severity, arm and leg strength, and bulbar function. However, motorized wheelchairs offer patients a greater sense of independence and an improved sense of well-being. CONCLUSION: Information obtained directly from wheelchair users with ALS provided first-hand experience concerning the most and least desirable features of wheelchairs and may help other ALS patients make informed decisions when purchasing a wheelchair.
Adult↗
Neonatal salivary cortisol in response to heelstick: method modifications enable analysis of low concentrations and small sample volumes.
Measuring cortisol in saliva offers important advantages compared to measurement in plasma or serum. However, the sampling procedure and also the detection limit cause problems, especially in paediatric and neonatal care. We describe a simple and efficient sampling procedure, together with a modification of a radioimmunoassay, which enables analysis of low (down to 1 nmol/L) concentrations of salivary cortisol (10 times lower detection limit than in the original procedure). This setting was used in studying salivary cortisol concentrations before and after heelstick on healthy newborn infants. A significant rise (median 81%; p<0.01) in salivary cortisol as response to this invasive stressor was noted.
Adrenal Glands↗
Prenatal bowel dilatation: congenital chloride diarrhoea.
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Chlorides↗
Properties of the mammalian and yeast metal-ion transporters DCT1 and Smf1p expressed in Xenopus laevis oocytes.
Transition metals are essential for many metabolic processes, and their homeostasis is crucial for life. Metal-ion transporters play a major role in maintaining the correct concentrations of the various metal ions in living cells. Little is known about the transport mechanism of metal ions by eukaryotic cells. Some insight has been gained from studies of the mammalian transporter DCT1 and the yeast transporter Smf1p by following the uptake of various metal ions and from electrophysiological experiments using Xenopus laevis oocytes injected with RNA copies (c-RNA) of the genes for these transporters. Both transporters catalyze the proton-dependent uptake of divalent cations accompanied by a 'slippage' phenomenon of different monovalent cations unique to each transporter. Here, we further characterize the transport activity of DCT1 and Smf1p, their substrate specificity and their transport properties. We observed that Zn(2+) is not transported through the membrane of Xenopus laevis oocytes by either transporter, even though it inhibits the transport of the other metal ions and enables protons to 'slip' through the DCT1 transporter. A special construct (Smf1p-s) was made to enhance Smf1p activity in oocytes to enable electrophysiological studies of Smf1p-s-expressing cells. 54Mn(2+) uptake by Smf1p-s was measured at various holding potentials. In the absence of Na(+) and at pH 5.5, metal-ion uptake was not affected by changes in negative holding potentials. Elevating the pH of the medium to 6.5 caused metal-ion uptake to be influenced by the holding potential: ion uptake increased when the potential was lowered. Na(+) inhibited metal-ion uptake in accordance with the elevation of the holding potential. A novel clutch mechanism of ion slippage that operates via continuously variable stoichiometry between the driving-force pathway (H(+)) and the transport pathway (divalent metal ions) is proposed. The possible physiological advantages of proton slippage through DCT1 and of Na(+) slippage through Smf1p are discussed.
Animals↗
Altered distribution of the yeast plasma membrane H+-ATPase as a feature of vacuolar H+-ATPase null mutants.
The effect of vacuolar H(+)-ATPase (V-ATPase) null mutations on the targeting of the plasma membrane H(+)-ATPase (Pma1p) through the secretory pathway was analyzed. Gas1p, which is another plasma membrane component, was used as a control for the experiments with Pma1p. Contrary to Gas1p, which is not affected by the deletion of the V-ATPase complex in the V-ATPase null mutants, the amount of Pma1p in the plasma membrane is markedly reduced, and there is a large accumulation of the protein in the endoplasmic reticulum. Kex2p and Gef1p, which are considered to reside in the post-Golgi vesicles, were suggested as required for the V-ATPase function; hence, their null mutant phenotype should have been similar to the V-ATPase null mutants. We show that, in addition to the known differences between those yeast phenotypes, deletions of KEX2 or GEF1 in yeast do not affect the distribution of Pma1p as the V-ATPase null mutant does. The possible location of the vital site of acidification by V-ATPase along the secretory pathway is discussed.
Cell Membrane↗