Ion transport processes in basolateral membranes of epithelia.
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Biomedical subjects
Publications and source records attributed to T C Cox.
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To study the mechanisms by which antidiuretic hormone and prostaglandins regulate Na transport at the apical membranes of the cells of anuran tissues, studies were done with fluctuation analysis. Epithelia of frog skin (Rana pipiens) were treated with vasopressin alone, or treated with vasopressin after inhibition of Na transport by indomethacin. The tissues were bathed symmetrically with a Cl-HCO3 Ringer solution and short-circuited continuously. In this experimental circumstance, the amiloride-induced current noise power density spectra were of the Lorentzian type with little or no l/f noise, provided that "scraped" skins were used for study. Despite large changes of Na transport, especially in epithelia treated with indomethacin and vasopressin, the single-channel Na current remained essentially unchanged, whereas the density of amiloride-inhibitable, electrically conductive Na channels was increased by vasopressin and decreased by indomethacin.
Transport and electrical characteristics of the isolated skin of larval Rana catesbeiana were analyzed using ion substitution and nystatin. When the inner (IBS) and outer (OBS) bathing solutions contained Na Ringer solution the electrical potential (TEP), short-circuit current (SCC), and resistance (R2) were 23.5 +/- 7.0 mV, 2.8 +/- 0.7 microA . cm-2, and 8.00 +/- 0.74 k omega. cm2, respectively (n = 4). When K was substituted for Na in the OBS these values were not changed significantly. When nystatin (120 U.cm-3), a drug that increases the permeability of membranes to small cations, was added to the OBS (Na Ringer) there was a striking increase in the TEP to 52.8 +/- 3.1 mV, SCC to 14.8 +/- 2.0 microA . cm-2, and drop in R2 to 3.75 +/- 0.52 k omega . cm2. The response to nystatin was similar with Na or K Ringer solution in the OBS (Na Ringer in the IBS). With Na Ringer in the OBS and IBS, the increase in SCC induced by low doses of nystatin equaled net Na flux measured isotopically. Plots of transepithelial conductance against SCC after nystatin were linear and provided estimates of shunt resistance (R*sh = 14.6 +/- 1.3 k omega . cm2) and electromotive driving force for ions (E*A = 76 +/- 3 mV). Similar curves were obtained with K Ringer in the OBS. In the presence of nystatin, characteristics of the basolateral membrane were evaluated. It displayed selective permeability to K relative to Na or Tris.
The kinetics of Na tracer fluxes were reinvestigated in isolated epithelia of frog skin in which the unstirred layers of the corium were removed. The rate of appearance of 22Na in the basolateral solution (JNa13) conformed to a single exponential for tracer buildup with a mean t1/2 of 1.9 min. The Na transport pool labeled isotopically from the apical solution was about 40 neq/cm2 for epithelia bathed in either a chloride or sulfate Ringer solution. Basolateral-to-apical solution unidirectional Na flux (JNa31) was low, averaging 0.7 microA/cm2 and remained low for 40 min of ouabain treatment of the epithelia. In agreement with electrophysiological data, ouabain at 10(-4) M caused an acute inhibition (less than 1 min) of the Na efflux at the basolateral membrane (JNa23), falling to 40.6 and 26.7% of control for epithelia bathed in Cl and SO4 Ringer, respectively. Although furosemide exerted little or no consistent effect on the Na flux of control epithelia, this drug in ouabain-poisoned epithelia caused a substantial inhibition of a neutral, chloride-dependent, ouabain-insensitive Na efflux. It is suggested that ouabain "induces" a neutral mechanism of Na transport at the basolateral membrane of the cells that is chloride dependent and furosemide sensitive.
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The theoretical risk of injuring the vertebral artery or anomalous vessels at lateral cervical puncture is assessed. In just less than 30% of vertebral arteries the vessel overlies the lateral aspect of the spinal canal between the first and second cervical vertebrae, usually the antero-inferior quadrant. Directing the spinal needle to the posterior third of the canal virtually eliminates the possibility of injuring this and most anomalous arteries traversing the region. The likelihood of inducing subarachnoid haemorrhage by injuring these vessels would appear to be considerably less in lateral cervical than in cisternal puncture.
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Carefully dissected, mounted, and bathed with Ringer solution, the larval bullfrog skin has a resistance of about 9,000 omega.cm2 and a stable transepithelial electrical potential of about 20 mV (inside +). A short-circuit current of about 2 microA.cm-2 is generated that is comparable in magnitude to the net inward flux of Na+. At open circuit the flux ratio equation for Na+ is not satisfied. Larval skin is less sensitive to ouabain, amiloride, and ADH than adult skin. The current-voltage (C-V) relationship across the preparation is not linear; there are distinct breaks in both the hyperpolarizing and hypopolarizing regions. The former break, at about +130 mV, corresponds with a break observed in adult skin that corresponds with ENa. The shunt resistance (RS) and active pathway resistance (RA) were estimated by C-V curve analysis and by ion substitution. The two methods yielded comparable values with RS about 11 k omega.cm2 and RA about 62 k omega.cm2. It is suggested that transport is limited by the number of entry sites for sodium at the apical border of transport cells.
Microphthalmia with linear skin defects (MLS) syndrome is an X-linked disorder presenting only in XX individuals. It is characterised by dysmorphic features such as microphthalmia, sclerocornea, and linear streaks of erythematous and hypoplastic skin restricted to the head and neck. Karyotype analyses have so far revealed a terminal deletion or translocation causing monosomy for the distal Xp region (Xp22.3) in all patients. We have used existing cosmid clones from the region to perform a saturation screen for AC-type microsatellites with the goal of facilitating analysis of five novel patients with features of MLS. Three of these cases had an Xp22.3 abnormality, while the other two showed some characteristic features of MLS but had apparently normal karyotypes. Forty-two novel microsatellite markers have now been developed from the 1.7 Mb cloned interval. Ninety-three percent of the novel markers exhibited allelic variation, representing an average of one polymorphic PCR-based marker (STR) every 41 kb.
Dural sinus thrombosis can be a difficult diagnosis to establish because it may present with nonspecific signs of raised intracranial pressure. Diagnosis by CT is well documented but signs may be subtle. Angiography is the "gold standard" but is invasive and requires a very high index of clinical suspicion to request. Magnetic resonance offers a method of demonstrating the dural sinuses in multiple planes and, furthermore, flow within the sinuses may be depicted by MR angiography. We report on three cases where the diagnosis of superior sagittal sinus thrombosis due to calvarial metastases was missed by CT, primarily due to their site over the convexity, but was demonstrated accurately using MR with MR angiography.
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PURPOSE: A pilot study to detect volume changes of cerebral structures in growth hormone (GH)-deficient adults treated with GH using serial 3D MR image processing and to assess need for segmentation prior to registration was conducted. METHOD: Volume MR scans of the brain were obtained in five patients and six control subjects. Patients were scanned before and after 3 and 6 months of therapy. Control subjects were scanned at the same intervals. A phantom was used to quantify scaling errors. Second and third volumes were aligned with the baseline by maximizing normalized mutual information and transformed using sinc interpolation. Registration was performed with and without brain segmentation and correction of scaling errors. Each registered, transformed image had the original subtracted, generating a difference image. Structural change and effects of segmentation and scaling error correction were assessed on original and difference images. The radiologists' ability to detect volume change was also assessed. RESULTS: Compared with control subjects, GH-treated subjects had an increase in cerebral volume and reduction in ventricular volume (p = 0.91 x 10(-3)). Scale correction and segmentation made no difference (p = 1 and p = 0.873). Structural changes were identified in the difference images but not in the original (p = 0.136). The radiologists detected changes >200 microm. CONCLUSION: GH treatment in deficient patients results in cerebral volume changes detectable by registration and subtraction of serial MR studies but not by standard assessment of images. This registration method did not require prior segmentation.
The computed tomography (CT) scans of 132 patients with late onset epilepsy were compared with the CT scans of an age- and sex-matched control group. Patients with neurologic symptoms in addition to epilepsy, patients with a definite antecedent cause for epilepsy, and patients with tumours on CT scanning were excluded. Fifteen of the patients with epilepsy, as opposed to two of the controls, had infarcts on their CT scans (p = 0.003 Fisher exact test, two-tailed). In nine of these patients only lacunar infarcts were present. No patient had a history of stroke. We concluded that cerebrovascular disease was the major underlying contributory factor to the development of epilepsy in these patients. Twelve of the 15 patients were aged greater than 60 years, representing 21% of the patients in this age group. There was no difference between the epileptic patients and controls in the presence of clinical features of systemic vascular and cardiac disease. CT scan evidence of cerebral atrophy was as common in the control subjects as in the patients with epilepsy.
We report the case of a man presenting with a brain-stem stroke from which he recovered fully, who developed right-sided weakness and numbness on walking despite no demonstrable postural fall in arterial blood pressure. Angiography revealed an occluded left vertebral artery, a tight stenosis at the origin of the right vertebral artery and non-patent left posterior communicating artery. Percutaneous transluminal angioplasty to the right vertebral stenosis results in a good angiographic result, and remission of symptoms which has persisted for 1 year. Identification of such patients with vertebrobasilar positional haemodynamic symptoms due to a focal stenosis is important as angioplasty offers an effective therapeutic option.
The authors report a case of cerebral siderosis, a rare disease that generally follows multiple small episodes of subarachnoid hemorrhage from any source, following long-term anticoagulation and minor head injury, and document the features on MR, which demonstrates characteristic hypointensity in the meninges on T2-weighted scans.