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Focal decline of cortical thickness in Alzheimer's disease identified by computational neuroanatomy.

Alzheimer's disease (AD) is characterized by a heterogeneous distribution of pathological changes throughout the brain. Magnetic resonance imaging can be used to investigate the regional distribution of cortical atrophy in AD in vivo. One marker for the disease-specific atrophy is the thickness of the cortical mantle across the brain, obtained with automated 3-D image processing. Here, we present data from 36 subjects (17 controls and, 19 patients diagnosed as probable AD) investigated for cortical thickness across the entire brain. We show significant cortical thickness decline in AD in temporal, orbitofrontal and parietal regions, with the most pronounced changes occurring in the allocortical region of the medial temporal lobes, outlining the parahippocampal gyrus, and representing a loss of >1.25 millimeters of cortical thickness. Moreover, focal cortical areas decline with progression of the disease as measured by time from baseline scan as well as the Mini-Mental State Exam. The results demonstrate the ability of this method to detect changes in cortical thickness in AD, across the entire brain, without need of prior anatomical definitions. The regional distribution of changes reported here is consistent with independent findings on the distribution of neuropathological alterations in AD. Using cortical thickness, moreover, we provide a direct quantitative index of atrophy in the disease.

Aged↗

Effects of (CO2 + HCO3-) on electrical conductance in cortical thick ascending limbs.

These experiments in isolated mouse cortical thick ascending limbs (cTALH) provide information about: the relative contributions of cellular and paracellular pathways to the transepithelial electrical conductance Ge (mS cm-2); the effects of (CO2 + HCO3-) on Ge; the ratio of net K+ secretion (JKnet) to net Cl- absorption (JClnet); and the K+ requirement for apical membrane furosemide-sensitive NaCl entry. The combination of luminal Ba++, zero K+ reduced Ge; at 5 mM luminal Ba++, the residual conductance was about 75% of the control Ge. The Ba++-insensitive Ge of 73.1 +/- 6.4 mS cm-2 was only slightly greater than the shunt conductance of 57 mS cm-2 computed from the sum of the dissipative bath to lumen fluxes of 22Na+ and 36Cl-. Moreover, luminal 5 mM Ba++, zero K+ had no effect on the Na+/Cl- permselectivity ratio of the paracellular pathway. Thus, Ba++ blockaded transcellular conductance by blocking apical membrane K+ channels. The combination of (CO2 + HCO3-) in external solutions increased Ge solely by augmenting the Ba++-sensitive, that is, transcellular, component of Ge. Finally, in paired experiments, the ratio JKnet/JClnet was 0.27 +/- 0.05; and both Ve, the spontaneous transepithelial voltage (mV), and the equivalent short circuit current Je (pEq sec-1 cm-2) were reduced dramatically by luminal K+ omission. Thus, apical membranes of the cTALH appear to contain a pathway for net K+ secretion, and apical membrane NaCl entry may involve co-transport with K+. Transcellular conductance contributes at least 25% to the total Ge, and the combination (CO2 + HCO3-) augments transcellular conductance.

Absorption↗

Meditation experience is associated with increased cortical thickness.

Previous research indicates that long-term meditation practice is associated with altered resting electroencephalogram patterns, suggestive of long lasting changes in brain activity. We hypothesized that meditation practice might also be associated with changes in the brain's physical structure. Magnetic resonance imaging was used to assess cortical thickness in 20 participants with extensive Insight meditation experience, which involves focused attention to internal experiences. Brain regions associated with attention, interoception and sensory processing were thicker in meditation participants than matched controls, including the prefrontal cortex and right anterior insula. Between-group differences in prefrontal cortical thickness were most pronounced in older participants, suggesting that meditation might offset age-related cortical thinning. Finally, the thickness of two regions correlated with meditation experience. These data provide the first structural evidence for experience-dependent cortical plasticity associated with meditation practice.

Adult↗

Cell density and cortical thickness in Heschl's gyrus in schizophrenia, major depression and bipolar disorder.

There is evidence that the superior temporal gyrus and Heschl's gyrus within it are implicated in schizophrenia. We investigated neuronal and glial cell density and cortical thickness within Heschl's gyrus, using the optical disector to estimate cell density within cortical layers 3 and 5 in tissue derived postmortem from people with diagnoses of major depressive disorder, schizophrenia and bipolar disorder, compared with normal controls (n=15 per group). No significant difference in neuronal or glial cell density or in cortical thickness was observed between the groups; our findings therefore provide no support for the presence of cellular pathology within Heschl's gyrus in schizophrenia.

Auditory Cortex↗

Basolateral membrane H/OH/HCO3 transport in the rat cortical thick ascending limb. Evidence for an electrogenic Na/HCO3 cotransporter in parallel with a Na/H antiporter.

Mechanisms involved in basolateral H/OH/HCO3 transport in the in vitro microperfused rat cortical thick ascending limb were examined by the microfluorometric determination of cell pH using (2',7')-bis-(carboxyethyl)-(5,6)-carboxyfluorescein. The mean cell pH in this segment perfused with 147 mM sodium and 25 mM HCO3 at pH 7.4 was 7.13 +/- 0.02 (n = 30). Lowering bath HCO3 from 25 to 5 mM (constant PCO2 of 40 mmHg) acidified the cells by 0.31 +/- 0.02 pH units at a rate of 0.56 +/- 0.08 pH units/min. Removal of bath sodium acidified the cells by 0.28 +/- 0.03 pH units at a rate of 0.33 +/- 0.04 pH units/min. The cell acidification was stilbene inhibitable and independent of chloride. There was no effect of bath sodium removal on cell pH in the absence of CO2/HCO3. Depolarization of the basolateral membrane (step increase in bath potassium) independent of the presence of chloride. Cell acidification induced by bath sodium removal persisted when the basolateral membrane was voltage clamped by high potassium/valinomycin. Although these results are consistent with a Na/(HCO3)n greater than 1 cotransporter, a Na/H antiporter was also suggested: 1 mM bath amiloride inhibited the cell pH defense against an acid load (rapid ammonia washout), both in the presence and absence of CO2/HCO3, and inhibited the cell acidification induced by bath sodium reduction from 50 to 0 mM. In conclusion, an electrogenic Na/(HCO3)n greater than 1 cotransporter in parallel with a Na/H antiporter exist on the basolateral membrane of the rat cortical thick ascending limb.

Amiloride↗

Longitudinal mapping of cortical thickness and brain growth in normal children.

Recent advances in magnetic resonance imaging (MRI) technology now allow the tracing of developmental changes in the brains of children. We applied computer-matching algorithms and new techniques for measuring cortical thickness (in millimeters) to the structural MRI images of 45 children scanned twice (2 yr apart) between the ages 5 and 11. Changes in brain size were also assessed, showing local brain growth progressing at a rate of approximately 0.4-1.5 mm per year, most prominently in frontal and occipital regions. Estimated cortical thickness ranged from 1.5 mm in occipital regions to 5.5 mm in dorsomedial frontal cortex. Gray matter thinning coupled with cortical expansion was highly significant in right frontal and bilateral parieto-occipital regions. Significant thickening was restricted to left inferior frontal (Broca's area) and bilateral posterior perisylvian (Wernicke's area on the left) regions. In the left hemisphere, gray matter thickness was correlated with changing cognitive abilities. For the first time, developmental changes in gray matter thickness, brain size, and structure-function relationships have been traced within the same individuals studied longitudinally during a time of rapid cognitive development.

Adult↗

Substrate utilization in the isolated perfused cortical thick ascending limb of rabbit nephron.

Isolated segments of cortical thick ascending limbs (cTAL) of rabbit kidney were perfused in vitro and the equivalent short circuit current (Isc) was measured. In a first series all substrates were removed on either side. Isc fell rapidly to 50 +/- 12% after 3 min and to 27 +/- 6% (n = 5) after 10 min. This indicates that in cTAL segments Isc is strictly dependent on the presence of substrates. In series two it was tested what substrates can be utilized by the cTAL segment, and from which epithelial side [bath (b) or lumen (1)] the substrates are taken up. From the 1-side only butyrate (10 mmol X 1(-1) sustained the Isc at 95 +/- 2% (n = 7). All other tested substrates (10 mmol X 1(-1): pyruvate, acetate, beta-OH-butyrate, D-glucose, and L-lactate lead to a marked decline in Isc. From the b-side several substrates (5--10 mmol X 1(-1) sustained the Isc: D-glucose, D-mannose, butyrate, beta-OH-butyrate, acetoacetate, L-lactate, acetate and pyruvate. Other compounds (1--10 mmol X 1(-1): citrate, alpha-ketoglutarate, succinate, glutamate, glutamine, propionate, caprylate and oleate did not sustain Isc. In the third series the mechanism of substrate utilization from the basolateral cell side was studied. It was shown that the Isc is a saturable function of the D-glucose, L-lactate, acetate, pyruvate or beta-OH-butyrate concentration with apparent Km's between 0.05--1.0 mmol X 1(-1). Several known inhibitors of sugar and of anion transport were tested at the bath side: phlorrhizin was without effect. Phloretin (500 mumol X 1(-1) inhibited Isc by 96%, yet its effect was not dependent on the presence of substrates on the b-side since inhibition occurred also if the b-perfusate contained no substrate and Isc was driven by luminal butyrate. Also SITS (5 mmol X 1(-1) exerted only a small inhibitory effect which was not specific since it was also observed with luminal butyrate. alpha-Cyano-m-OH-cinnamate (10 mmol X 1(-1) inhibited the Isc specifically when L-lactate was the bath substrate. Probenecid (1 mmol X 1(-1) had a similar yet less marked inhibitory effect. The D-glucose uptake from the b-side was specifically inhibited by cytochalasin B at 5 X 10(-6) mol X 1(-1). We conclude that the cTAL segment of the rabbit utilizes D-glucose and/or small anions such as pyruvate or L-lactate or acetate to energize salt reabsorption.(ABSTRACT TRUNCATED AT 400 WORDS)

Absorption↗

Combined cortical thickness and bone density determination by photon absorptiometry.

Bone cortical thickness and density were measured in rat femurs in vitro by a photon absorptiometry technique. A scan perpendicular to the long bone axis using photons from highly collimated 109Cd or 125I sources yielded the bone wall thickness and attenuation at mid-shaft. A second scan after the bone was rotated axially 90 degrees was taken to measure the wall or shaft thickness identically responsible for the mid-shaft attenuation of the first scan. The mid-shaft attenuation of the second scan was due to the bone thickness derived from the first scan; thus two complementary measurements are derived by this technique. The bone density is then directly calculated with an estimated accuracy of 10% (coefficient of variation) using empirically determined mass attenuation coefficients. Measurements of mass attenuation coefficients of ashed and dried samples were compared with calculated coefficients for estimated bone composition. Results indicate that the mass attenuation coefficient for bone in vivo can be well estimated such that bone density can be accurately derived from this technique.

Animals↗

[Correlation between roentgen morphometrically obtained data and cortical thickness indicative of anchorage strength of screws in human cadaver vertebral bodies].

Through the morphometric and histomorphometric examinations on the vertebral of the corpses, a functional connection between roentgenmorphometric plain facts (in transverse- and sagittal diameter of the vertebral body) and the cortical thickness can be established. The stress of the vertebral body through a screw can already preoperatively be assessed by roentgenmorphometric examinations that the cortical thickness plays an important dimension in the anchorage tightening of the screws on the vertebral body. By use of this knowledge the guarantee of operation on vertebral body is raised.

Adolescent↗

Stimulation of NaCl reabsorption by antidiuretic hormone in the cortical thick ascending limb of Henle's loop of the mouse.

The effect of antidiuretic hormone (ADH) on transepithelial Na+ Cl-, Ca2+ and Mg2+ net fluxes (JNa, JCl, JMg, JCa) was investigated in isolated perfused cortical thick ascending limb segments (cTAL) of the mouse nephron, using the microperfusion technique and the electron microprobe analysis to determine the ionic composition of the collected tubular fluid. Simultaneously, the transepithelial potential difference (PDte) and the transepithelial resistance (Rte) were recorded. Prior to the flux measurements cTAL segments were perfused for one hour. During this equilibration period PDte decreased significantly from +19.9 +/- 1.6 to +14.9 +/- 1.1 mV and Rte increased from 30.6 +/- 3.5 omega cm2 to 38.8 +/- 2.4 omega cm2 (n = 7), reflecting a decline in NaCl transport. After ADH was added to the bath solution at 10(-10) mol.l-1, PDte increased from +14.4 +/- 1.1 to +18.0 +/- 1.5 mV, accompanied by a rise in JNa and JCl from 205 +/- 11 to 273 +/- 19 and from 216 +/- 12 to 283 +/- 21 pmol.min-1.mm-1 (n = 7), respectively. JCa and JMg also increased from 0.81 +/- 0.07 to 1.50 +/- 0.12 and from 0.43 +/- 0.11 to 0.76 +/- 0.08 pmol.min-1.mm-1 (n = 7), respectively. All these effects were fully reversible after withdrawal of the hormone. In conclusion our data indicate that ADH stimulates divalent cation transport and NaCl transport in the cortical thick ascending limb of Henle's loop of the mouse.

Animals↗

Cortical thickness and trabecular pattern of the femoral neck as a measure of osteopenia.

The pelvic radiographs of 312 patients aged 18 to 92 years were reviewed to determine if the Singh index was valid or not. The cortical thickness of the lower part of the femoral calcar, the stress index (body weight, physical activity, and femoral neck angle), and the Singh Index (trabecular pattern of the femoral neck) were measured in each patient and correlated with each other and with the patient's age, sex, and dominant side. It was found that the Singh index correlates well with age but not with the cortical thickness or stress index. Thus, the Singh index is an unreliable measure of osteopenia, and we conclude that other methods should be used for screening patients with osteoporosis.

Adolescent↗

[Cortical thickness of the mandible with special reference to miniplate osteosynthesis. Morphometric analysis of autopsy material].

Thirty-two human mandibles were marked with three typical fracture lines: a low condylar fracture, a fracture of the mandibular angle, and one through the mental foramen on each side. The mandibles were sectioned at the fixation sites of the miniplate screws. The thickness of the cortical layer was measured with a scaled magnifying glass at the points of anthropological interest and at the marked screw holes. The inferior cortical layer turned out to be thickest in the anterior area. In contrast, it was very thin at the mandibular angle, which might explain the higher complication rate in treating fractures in this region. The thickness of the lingual cortex increased up to the symphysis, whereas the buccal cortical layer showed a decline in size from the mandibular angle up to the chin. The cortical bone at the alveolar ridge was porous. The cortical supply for miniplate osteosynthesis at the condylus ranged from 1.1 mm up to 1.74 mm, which seems to be limited, but due to the small diameter of the condylus most common screws obtain additional anchorage in the inner cortex. The thickness of the cortical layer at the mandibular angle increased from 1.47 mm at the ramus up to 1.97 mm at the beginning of the corpus, reaching 2.14-2.38 mm for the lower plate at the mental foramen. The results for the upper plate were slightly lower.

Bone Plates↗

Hormone-mediated Ca2+ transients in isolated renal cortical thick ascending limb cells.

Peptide hormones control salt reabsorption in cortical thick ascending limb (cTAL) cells of the loop of Henle. These agonists act, in part, through alterations on intracellular Ca2+ ([Ca2+]i). Primary cell cultures were prepared from porcine kidneys using a double antibody technique (goat antihuman Tamm-Horsfall and rabbit antigoat IgG antibodies). [Ca2+]i was determined in single cells with fluorescent techniques using fura-2. Parathyroid hormone (PTH) and arginine vasopressin (AVP) transiently increased [Ca2+]i in a dose-dependent manner. [Ca2+]i maximally increased from 85 +/- 5 nmol/l to 608 +/- 99 nmol/l with PTH, 10(-6) M, and to 766 +/- 162 nmol/l with AVP, 10(-7) M. The increment in [Ca2+]i by both hormones was by intracellular Ca2+ release and entry through plasma membrane Ca2+ channels. 8-Bromo-adenosine-3',5'-cyclic monophosphate (8-BrcAMP), 10(-4) M, increased [Ca2+]i (basal 83 +/- 3 to 427 +/- 121 nmol/l) but only from internal sources as nifedipine (10 mumol), ([Ca2+]i changes: 86 +/- 4 to 390 +/- 29 nmol/l) and removal of bath Ca/+o, ([Ca2+]i changes: 84 +/- 6 to 517 +/- 142 nmol/l), were without effect on agonist-induced [Ca2+]i. Thapsigargin, 1.5 mumol, completely abolished the AVP- and cyclic adenosine monophosphate-(cAMP)-induced Ca2+ transients, and partially inhibited PTH-mediated Ca2+ transients by about 50%. Pretreatment with 8-BrcAMP inhibited the PTH and AVP responses likely through depletion of cAMP-sensitive Ca2+ stores. Activation of protein kinase C (PKC) with phorbol esters inhibited PTH and AVP responses and 8-BrcAMP-induced [Ca2+]i transients.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Effect of cortical thickness and cancellous bone density on the holding strength of internal fixator screws.

Internal fixators are a new class of implants designed to preserve the periosteal blood supply of the bone. In contrast to conventional plate fixation in which the screws have spherical heads and are loaded mainly by axial pullout forces, screws in internal fixators are "locked" within the plate and therefore subjected to axial as well as bending loads. In this study the ultimate loads of screws of a commercially available internal fixator system were tested in a pullout (n = 72) and cantilever bending mode (n = 72) in metaphyseal and diaphyseal regions of four pairs of human tibiae with different bone qualities. Cortical thickness and cancellous bone density were determined at the screw insertion sites. Stepwise multiple linear regression revealed that cortical thickness and cancellous density can explain 93% and 98% of the variance of the ultimate load of the screws in an axial pullout and cantilever bending mode. Screws in internal fixators are better suited to transmit shear forces and thereby make better use of the strength potential of bone than screws used in conventional plate fixation: this is especially advantageous when bone strength is reduced, e.g. due to osteoporosis.

Aged↗

Measurements of macula densa cell volume changes in isolated and perfused rabbit cortical thick ascending limb. II. Apical and basolateral cell osmotic water permeabilities.

Cortical thick ascending limbs containing macula densa plaques were dissected and perfused in vitro. Macula densa cell osmotic water permeability of the apical and basolateral membranes were measured by setting up osmotic steps across them in less than 0.1 s and following the ensuing time-dependent cell volume changes. The results of this study are in accordance with the view that the macula densa cells have a relatively low permeability to water. Apical and basolateral osmotic water permeabilities are 2.4 and 30.4 x 10(-4) cm3 s-1 osMolar-1 cm-2 basement membrane area, respectively. No infoldings were taken into consideration. These water permeabilities were not affected by maximal and supramaximal doses of vasopressin. This paper provides new insight into the physiological behaviour of this small, and almost inaccessible, sensing epithelial disc of cells which improves the understanding of its participation in the juxtaglomerular feedback response.

Animals↗

Magnesium transport in the cortical thick ascending limb of Henle's loop of the rabbit.

Isolated cortical thick ascending limbs of Henle's loop were perfused in order to directly evaluate magnesium transport in this segment. Transepithelial potential difference was altered by varying the NaCl concentration in perfusate and bath and adding 50 microM furosemide to the perfusate. Perfusion under standard conditions with isotonic solutions resulted in a mean transepithelial potential difference of +8.8 +/- 0.7 mV and net magnesium absorption at a rate of 0.32 +/- 0.06 pmol/mm per min. Perfusion with a hypotonic solution significantly increased potential difference and the net absorptive rate of magnesium, calcium, and potassium. Conversely, reversal of the polarity of the potential difference with low NaCl bath and luminal furosemide produced net secretion of magnesium, calcium, and potassium. Parathyroid hormone in a bath concentration of 1.0 U/ml increased magnesium absorption from 0.32 +/- 0.06 to 0.63 +/- 0.06 pmol/mm per min (P less than 0.001) and calcium from 0.52 +/- 0.08 to 0.97 +/- 0.08 pmol/mm per min (P less than 0.001). Dibutyryl cyclic AMP produced similar effects on both calcium and magnesium absorption. Increasing bath calcium concentration twofold significantly inhibited net calcium absorption from 0.79 +/- 0.27 to 0.16 +/- 0.02 pmol/mm per min but magnesium transport was unaffected. Increasing bath magnesium concentration twofold significantly inhibited net magnesium absorption from 0.56 +/- 0.14 to -0.09 +/- 0.13 pmol/mm per min but had no effect upon net calcium transport. Net absorption of magnesium was significantly increased with increased concentration in the perfusate but calcium transport was unchanged. Similarly, increasing perfusate calcium concentration produced an increase in net calcium transport but did not alter magnesium transport. These data indicate that this segment of the loop of Henle is an important site for magnesium transport. Transport is influenced by luminal and bath concentration and is stimulated by parathyroid hormone and cyclic AMP. The data do not provide support for the concept of an interactive process between calcium and magnesium, and suggest that the positive transepithelial voltage is an important driving force for net reabsorption of magnesium, as well as calcium and potassium in this segment.

Animals↗

Bumetanide inhibition of [CO2 + HCO3]-dependent and -independent equivalent electrical flux in renal cortical thick ascending limbs.

Experiments were performed on single perfused segments of cortical thick ascending limbs of Henle isolated from mouse kidney in order to evaluate the interaction of bumetanide with apical membrane [CO2 + HCO3]-dependent and -independent sodium uptake. In this nephron segment [CO2 + HCO3]-dependent apical membrane salt uptake is accomplished by parallel Na+/H+ and Cl-/HCO3- exchange whereas [CO2 + HCO3]-independent salt uptake results from NaCl cotransport. Tubules were perfused and bathed at 37 degrees C in either [CO2 + HCO3]-buffered solutions (KRB) or with 4-(2-hydroxy(ethyl)-1-piperazineethanesulfonic acid-buffered external media (KRH) at pH 7.4. The spontaneous transepithelial voltage was measured through one-half of a double-barreled perfusion pipette and bipolar d.c. current pulses were delivered through the other half in order to measure the transepithelial conductance (milliSiemens per squared centimeter). The rate of net NaCl absorption was estimated from the electrical flux (Je) and was calculated from the equivalent short-circuit current. Cumulative dose-response data over the range 10(-7) to 10(-4) M luminal bumetanide were obtained in individual tubules in both KRB and KRH solutions. Significant inhibition of transepithelial voltage and Je obtained at 5 X 10(-7) M bumetanide (in KRB) to 10(-6) M (in KRH). When the effect of [CO2 + HCO3] per se on Je was subtracted from the bumetanide-induced inhibition, the two dose-response curves converge.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Failure properties of suture anchors in the glenoid and the effects of cortical thickness.

The ultimate pullout strength and fatigue properties of a screw-design suture anchor implanted in the anterior glenoid rim were investigated and compared with results from a nonscrew-design suture anchor. Twenty-two cadaveric glenoids were harvested and one to two anchors were implanted in the superior and inferior quadrants. Fifty-seven Statak 3.5 anchors (Zimmer, Warsaw, IN) were tested and compared with results obtained in a previous study on 50 Mitek GII anchors (Mitek Products, Inc, Westwood, MA). The specimens were mounted on an Instron fatigue testing machine (Instron Corp, Canton, MA) and cycled between preselected minimum and maximum loads until pullout. The Mitek GII maintained a higher pullout strength than the Statak 3.5 after cyclic loading. Cortical thickness at the implantation sites was measured, and found to decrease monotonically from superior to inferior positions. The ultimate pullout strength, and subsequently the fatigue life, of both types of suture anchors depended directly on cortical thickness. The significantly lower performance of both anchors when placed inferiorly emphasizes the importance of correct anchor selection, number, and placement in this region. All anchors settled during the first 10 to 100 cycles, resulting in partial exposure of the implant. Intraoperative cycling of the anchors before suture tying may be necessary to achieve complete settling and prevent subsequent loss of coaptation between capsule and glenoid. The study shows that for the anchors to last 1,000 cycles or more, less than 50% of the theoretical ultimate pullout strength should be applied cyclically. With aggressive early rehabilitation exercises, this significant decrease in fixation strength could shift reconstruction failure from suture breakage or soft tissue tearing to anchor pullout.

Aged↗