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61.
We used the whole-cell configuration of the patch-clamp technique and cultured ventricular myocytes from 7-day embryonic chicks to test the hypothesis that sialic acid residues (NANA) constitute the negative surface charge associated with delayed rectifier potassium channels. Delayed rectifier current (iK) was elicited at potentials between -40 and +60 mV. The existence of negative fixed charges close to the "gating sensor" was confirmed by a 6.8-mV negative shift of the half-activation potential (V1/2) following a 10-fold reduction of divalent cations and a 22.6-mV position shift following the addition of 10 mM NiCl2. An 8.4-mV increase in the Boltzmann equation slope factor (k) in the former experiment and a 5.5-mV decline in the latter suggested that the surface charge is not uniformly distributed. We used a high performance liquid chromatography procedure to detect freed sarcolemmal NANA and found that 71-88% was released by neuraminidase (0.2-2.0 U/ml) during 1-h treatments. Such treatments had no significant effect upon the amplitudes of iK or V1/2. On the other hand, k was increased significantly by the enzyme (2.0 U/ml), but only when Ca2+ was present. Finally, 1-h pre-treatments with neuraminidase (2.0 U/ml) had no effect on the positive shift of V1/2 induced by Ni2+. We conclude that although sarcolemmal NANA may bind Ca2+, it does not constitute the surface charge of delayed rectifier potassium channels. 相似文献
62.
Andrew I. Jun Wyman T. McGuirt Raul Hinojosa Glenn E. Green Nathan Fischel‐Ghodsian Richard J. H. Smith 《The Laryngoscope》2000,110(2):269-269
Objective: Mutations in GJB2, a gene that encodes a gap junction protein, Connexin 26 (Cx26), are responsible for approximately one third of sporadic severe‐to‐profound or profound congenital deafness and half of severe‐to‐profound or profound autosomal recessive nonsyndromic hearing loss (ARNSHL). Mouse mutants homozygous for knockouts of this gene are nonviable, precluding histopathologic studies of the associated inner ear pathology in this animal model. Therefore, we studied archival temporal bone sections to identify temporal bone donors with Cx26‐related deafness. Study Design: Temporal bone donors with a history of congenital severe‐to‐profound or profound deafness were identified in the registry of the Temporal Bone Library at the University of Iowa. Histological findings were interpreted in a blinded fashion. DNA extracted from two celloidin‐embedded mid‐modiolar sections from each temporal bone was screened for the 35delG Cx26 mutation. The entire coding region of Cx26 was screened for other deafness‐causing mutations if the 35delG mutation was detected. Results: Of five temporal bone donors with congenital severe‐to‐profound deafness, one donor was found to have Cx26‐related deafness. This individual was a Cx26 compound heterozygote, carrying the 35delG mutation and a noncomplementary Cx26 missense mutation on the opposing allele. Microscopic evaluation of this temporal bone showed no neural degeneration, a good population of spiral ganglion cells, near‐total degeneration of hair cells in the organ of Corti, a detached and rolled‐up tectorial membrane, agenesis of the stria vascularis, and a large cyst in the scala media in the region of the stria vascularis. Conclusion: This study is the first to report the temporal bone histopathology associated with Cx26‐related deafness. Preservation of neurons in the spiral ganglion suggests that long‐term successful habilitation with cochlear implants may be possible in persons with severe‐to‐profound or profound Cx26‐related deafness. 相似文献
63.
Progressive amplification and overexpression of the eukaryotic initiation factor 4E gene in different zones of head and neck cancers. 总被引:9,自引:0,他引:9
D L Sorrells G E Ghali A De Benedetti C A Nathan B D Li 《Journal of oral and maxillofacial surgery》1999,57(3):294-299
PURPOSE: Eukaryotic initiation factor 4E (eIF4E) binds to mRNA as the initial rate-limiting step in protein synthesis. Amplification and overexpression of the eIF4E gene has been associated with malignant transformation. The objectives of this study were to 1) quantify the eIF4E gene in head and neck squamous cell carcinoma (HNSCC) specimens, 2) quantify eIF4E protein elevation and examine its association with eIF4E gene amplification, and 3) determine whether there is progression in eIF4E gene amplification and protein overexpression in the tumor-free resection margin, the transition zone, and the tumor core of HNSCC specimens. MATERIALS AND METHODS: Eighteen HNSCC specimens were divided into three zones: 1) tumor core; 2) transition zone; and 3) "tumor-free" margin. Competitive polymerase chain reaction was performed to determine eIF4E gene copy number. eIF4E protein expression was quantified using Western blot analysis. RESULTS: All 18 HNSCC specimens tested had significant eIF4E gene amplification (4.3+/-1.2; P < .05). In contrast, none of the 10 benign specimens from noncancer patients had any eIF4E gene amplification (1.1+/-0.5). In the 12 HNSCC specimens examined for the three zones, the tumor core and transition zone showed eIF4E gene amplification (5.2+/-1.1 and 3.5+/-0.9, respectively) compared with the "tumor-free" margin (2.1+/-1.1; P < .05). The tumor core and transition zone showed significant efF4E protein elevation (15.5+/-9.3, 4.4+/-4.6, respectively) compared with the "tumor-free" margin (0.9+/-0.5, P < .05). CONCLUSIONS: The eIF4E gene is amplified and overexpressed in HNSCC. Amplification and elevation of eIF4E were highest in the tumor core, intermediate in the transition zone, and lowest in the tumor-free margin. There appears to be progression of eIF4E gene amplification and overexpression from the "tumor-free" margin to the tumor core. 相似文献
64.
The hormone melatonin is secreted at night from the pineal gland, with light being a potent inhibitor of its secretion. Age related decreases in plasma melatonin concentrations have indicated that this may be related to pineal calcification with aging. Recently, it was shown that the melatonin sensitivity to light may be a biological marker of bipolar disorder. However, on average, patients were older than the control group in most studies, and it is not known if age has an effect on the melatonin suppression by light. To test this hypothesis, the present study investigated the effect of age on the melatonin sensitivity to dim light (200 lux). Participants were grouped into three age groups. On the testing night, they were placed in a dark room from 21.00 h to 02.30 h. Light exposure was for an hour from midnight to 01.00 h. Blood samples were collected at regular intervals for measurement of plasma melatonin. No significant differences were found in the percentage suppression of melatonin within the age groups defined in the present study (P > 0.5). No correlation was also found between age and percentage suppression of melatonin (r2 = 0.007; P > 0.1). Our results suggest that the melatonin suppression by light (200 lux) is not affected by age. 相似文献
65.
Fascicular tachycardia sensitive to calcium antagonists 总被引:3,自引:0,他引:3
Five patients with recurrent tachycardias exhibiting right bundlebranch block with left axis deviation were referred for investigation.In each case, a supraventricular mechanism was suspected. Duringsinus rhythm, the QRS morphology and axis (10 to +60degrees) and HV intervals were normal. Tachycardia was initiatedby timed ventricular premature stimuli in 4 patients, rapidventricular pacing in 3 patients and rapid atrial pacing in2 patients. The tachycardia cycle length varied from 275 to380 ms with right bundle branch block and a leftward axis changeof 30 to 125 degrees at the onset of the tachycardia. The HVinterval ranged from +15 to 20 ms. In each patient ventriculoatrialdissociation occurred spontaneously or could be induced. Alltachycardias could be terminated or greatly slowed by calciumantagonists. These data are consistent with an unusual reentrantmechanism of tachycardia located in the posterior fascicle ofthe left bundle branch. 相似文献
66.
Depression of the fast IPSP underlies paired-pulse facilitation in area CA1 of the rat hippocampus. 总被引:5,自引:0,他引:5
1. Intracellular recordings from CA1 pyramidal neurons in the rat hippocampal slice have been used to study synaptic transmission after maximal orthodromic stimulation of the Schaffer collateral-commissural fibers. Paired-pulse stimulation was used to investigate how the first (conditioning) stimulation influenced the response to the second (test) stimulation. 2. When the test stimulation was delivered up to approximately 4 s after the conditioning stimulation, the late phase of the excitatory postsynaptic synaptic potential (EPSP) was increased ("late-phase facilitation") whereas the fast (f-) and the slow (s-) inhibitory postsynaptic potentials (IPSPs) were depressed. 3. In terms of appearance and time course, facilitation of the intracellularly recorded EPSP was similar to that of the extracellularly recorded field EPSP in stratum radiatum. 4. The s-IPSP is not involved in facilitation of the EPSP. To show this, we counteracted the s-IPSP either by repolarizing the membrane potential to the resting level or by intracellularly injecting the quaternary lignocaine derivative QX 314. Facilitation of the late phase of the EPSP was unaffected by either procedure. 5. The conditioned response was modified in two ways when the stimulation was delivered at the equilibrium potential for the f-IPSP (Ef-IPSP) and the s-IPSP had been blocked by intracellular injection of QX 314. The amplitude of the EPSP was increased, and the repolarizing phase was delayed with an apparent depolarizing shift of Ef-IPSP. This effect was present at pulse intervals greater than 20 ms and was maximal after 150 ms. Facilitation could be detected at interpulse intervals of up to 4 s. 6. The gamma-aminobutyric acid-B (GABAB) agonist baclofen (1 microM) reduced late-phase facilitation by preferentially increasing the unconditioned response, such that this came to resemble a conditioned response in control medium. 7. The f-IPSP was isolated pharmacologically to investigate its role in the facilitation of the EPSP. This was done by blocking the s-IPSP with QX314 and the EPSP with a mixture of the N-methyl-D-aspartate (NMDA) receptor blocker, 2-amino-5-phosphonovaleric acid (APV, 50 microM), and the non-NMDA receptor blocker 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX, 10 microM). An f-IPSP was then evoked by stimulating the interneurons directly. This potential could be blocked by the GABAA receptor antagonist bicuculline (20 microM), thereby confirming the successful isolation of GABAAergic transmission. 8. With paired-pulse stimulation, the amplitude of the conditioned f-IPSP was depressed.(ABSTRACT TRUNCATED AT 400 WORDS) 相似文献
67.
Richard S. Elloway Martin P. Jacobs Milton F. Nathan Joseph C. Mantil 《European journal of nuclear medicine and molecular imaging》1992,19(2):113-118
We combined edrophonium provocative testing with the technique of radionuclide oesophageal transit (RET) in 30 consecutive patients with non-cardiac chest pain (NCCP) and 12 controls. The oesophageal transit time of aqueous technetium-99m sulfur colloid was determined before and after intravenous infusion of 80 g/kg edrophonium chloride (ED). Patient symptoms during provocative RET (P-RET) were recorded. Thirteen (43%) of the patients had abnormal study results, whereas all control subjects had normal results. Three groups considered abnormal were observed: (a) in two patients (6%), the pain was reproduced and transit pre- and post-ED administration was prolonged (>15 s); (b) in six patients (20%), the pain was reproduced, but transit was normal pre- and post-ED; (c) in five patients (17%), transit pre- and post-ED was prolonged, but no pain was reproduced. In five patients (17%), ED prolonged the transit time > 15 s without pain, but the baseline transit was normal. Transit time was measurable in 23 patients. Mean pre-ED transit time was 10.2 ± 7.4 s (mean ± SD) and post-ED, 12.4 ± 8.0 s (P=0.3). We conclude that ED has no significant effect on transit time, and the pain induced by ED rarely correlates with an abnormal transit; P-RET provides additional information to baseline RET, increasing sensitivity, and may be a useful screening method in the evaluation of patients with NCCP. 相似文献
68.
Association of HbA1c with prevalent cardiovascular disease in the original cohort of the Framingham Heart Study. 总被引:2,自引:0,他引:2
We studied the cross-sectional relationship between HbA1c and cardiovascular disease (CVD) in the survivors of the original cohort of the Framingham Heart Study (n = 1045). HbA1c was significantly related to prevalent CVD among women but not men. HbA1c was also related to hypertension and to the ratio of total to high-density lipoprotein cholesterol levels. In regression analyses that controlled for these and other potential risk factors, HbA1c remained significantly related to CVD among women. The relative odds of CVD increased 1.39-fold (95% confidence interval 1.06-1.83) for increases in HbA1c of 1% (e.g., for HbA1c from 5 to 6%). The relationship was not weakened when known diabetic subjects or subjects taking beta-blocker or thiazide medications were excluded from analysis. In contrast, there was no significant relationship between "casual" blood glucose and prevalent CVD. Our results reveal a strong, significant, independent association between hyperglycemia, measured by HbA1c, and CVD among older women. 相似文献
69.
Natham B 《Obesity surgery》1992,2(3):217-218
Medieval medical views on obesity are presented from Avicenna's Canon of Medicine. Health risks associated with obesity were appreciated, including respiratory and cardiovascular problems, infertility and
even sudden death. 相似文献
70.
Overexpressed eIF4E is functionally active in surgical margins of head and neck cancer patients via activation of the Akt/mammalian target of rapamycin pathway. 总被引:10,自引:0,他引:10
Cherie-Ann O Nathan Nazanin Amirghahari Fleurette Abreo Xiaohua Rong Gloria Caldito M Lamar Jones Huijuan Zhou Melanie Smith Donnellan Kimberly Jonathan Glass 《Clinical cancer research》2004,10(17):5820-5827
PURPOSE: Overexpression of eIF4E in surgical margins of head and neck cancer patients is an independent risk factor for recurrence. We hypothesize that overexpressed eIF4E is functionally active in tumor margins through activation of the Akt/mammalian target of rapamycin (mTOR) pathway EXPERIMENTAL DESIGN: Western blots and/or immunohistochemistry were performed to determine whether phosphorylation of mTOR and activation of its downstream molecules eIF4E-binding protein-1 (4E-BP1) and p70 S6 kinase and the upstream modulator of mTOR, Akt, were expressed in margins overexpressing eIF4E. RESULTS: There was a significant association between phospho-4E-BP1 and eIF4E expression of a margin or a significant difference in phospho-4E-BP1 expression between the eIF4E-positive and -negative margins (P < 0.01). A significant association between eIF4E and phospho-p70 S6 kinase as well as eIF4E and phospho-mTOR was also noted (P < 0.05). Western blot analysis indicated a highly significant difference in the phosphorylation status of 4E-BP1 between tumors and resection margins. A total of 89% of the 4E-BP1-expressing margins expressed more of the phosphorylated (beta, gamma, and delta) isoforms, whereas 81% of the 4E-BP1-expressing tumors expressed more of the unphosphorylated alpha isoform. A similar difference in Akt activation was noted between eIF4E-positive margins and tumors (P < 0.05). CONCLUSIONS: Overexpression of eIF4E is functionally active in tumor margins through activation of the Akt/mTOR signaling pathway. The greater degree of expression of downstream targets and upstream regulators of mTOR in margins compared with the tumors indicates preferential activation of the Akt/mTOR signaling pathway in margins overexpressing eIF4E. Rapamycin analogs can potentially be used as adjuvant therapy for patients with eIF4E-positive margins. 相似文献