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At least 19 recordsLinked to original sources
PubMed1991

The clinical course of osteoporosis in anorexia nervosa. A longitudinal study of cortical bone mass.

Women with anorexia nervosa have reduced bone mass and may develop fractures. Neither the pathophysiology of this osteoporosis nor its natural history is known. To study the clinical course of osteoporosis, we followed up 27 women with anorexia nervosa for a median of 25 months (range, 9 to 53 months). At study entry, cortical bone density, measured by single-photon absorptiometry of the radial shaft, was low (mean +/- SD, 0.63 +/- 0.07 g/cm2) and inversely related to the duration of amenorrhea (r = -0.49). During follow-up, most patients gained weight (n = 19), took calcium supplements (n = 16), and exercised regularly (n = 22), but fewer than half reached 80% or more of ideal body weight (n = 11), resumed menses (n = 6), or received estrogen (n = 4). Cortical bone density was stable during follow-up for the group as a whole; the mean annual change (+/- SD) was +0.005 (+/- .015) g/cm2 (95% confidence interval, -0.0009 to +0.0109). There was no significant difference in the mean change in bone density between women who attained 80% of ideal weight and those who did not or between groups who did or did not regain menses, take estrogen or calcium, or exercise vigorously. Four fractures were clinically observed in three women during follow-up. The rate of 0.05 nonspine fractures per person-year (95% confidence interval, 0.02 to 0.13) exceeds that of normal women in this age range (relative risk, 7.1; 95% confidence interval, 3.2 to 18.5). We conclude that reductions in cortical bone density appear not to be rapidly reversed by recovery from anorexia nervosa and that anorectic women may have an increased risk of fracture.

Adult↗
PubMed1990

The initiation of development at fertilization.

As seen, important advances have now been made in understanding the beginning of development at fertilization. Free calcium and pHi level changes result from a sperm-mediated breakdown of PPI with production of IP3. The resultant calcium increase, either alone or in concert with diacylglycerol, activates the Na(+)-H+ exchange and a consequent cytosolic pHi level increase. The calcium increase is responsible for the NADP change (via NAD kinase) and possibly the change in G6PD. These two changes could be involved solely in producing NADPH for fertilization membrane hardening or these changes could also have some role in the later initiation of DNA synthesis. The finding that other enzymes assayed in permeabilized cells also evince large changes in activity suggests that a global change may be occurring with important portents for cell activity. The role of calcium in furthering subsequent synthetic events, however, is unclear since no calcium target has yet been described that is necessary for the subsequent specific synthesis of proteins, as cyclins, or for the initiation of DNA synthesis. The pHi level increase, in concert with increased calcium, might be sufficient to start off protein synthesis and subsequent cyclin accumulation. However, the pHi level increase, independently of protein synthesis, can initiate new DNA synthesis. These independent events converge in the putative activation of MPF by cyclin, which then starts off the first mitotic cycle. Other independent events are associated with the sperm entry, cortical modifications, fertilization membrane elevation and the numerous changes leading to the fusion of the sperm and egg nucleus in the egg center. Fertilization represents one of the best studied examples of how a covert developmental program is made overt by an external messenger. The challenges for the near future are to explain how sperm-egg contact leads to PPI hydrolysis and how pHi level changes (and Cai level changes?) lead to the initiation of the cell cycle. The challenge for the distant future is describing how this program is set up during oogenesis.

Animals↗
PubMed1989

Stereotactic craniotomy: methods and results using the Brown-Roberts-Wells stereotactic frame.

Combining the power of stereotactic precision with open craniotomy in a stereotactic craniotomy technique decreases surgical time, morbidity, and postoperative hospitalization. Indications for its use are deep intrinsic masses 3.5 cm or less in diameter; small, superficial lesions otherwise difficult to localize; and lesions associated with motor, visual, or speech areas. Using the standard Brown-Roberts-Wells system allows a) precisely planned cortical entries, b) gross total lesion excisions under direct vision, c) use of probe-guided resection margins, d) small craniotomies through linear incisions, and e) use of local anesthetic alone for resections. The method and results of this universally available and relatively inexpensive technique are discussed in reference to 20 patients.

Adolescent↗
PubMed1990

The kappa-opiate agonist U50488H decreases the entry of 45Ca into rat cortical synaptosomes by inhibiting N- but not L-type calcium channels.

The selective kappa-opiate agonist U50488H (1-100 microM) significantly reduced the uptake of 45Ca into cortical synaptosomes from the brain of the rat, in a time- and dose-dependent manner. In physiological medium, the maximum inhibition occurred after 2 min; this was approximately 55% (at 100 microM) and the IC50 was 80 nM. Nifedipine (1 microM) had no significant effect on the influx of Ca2+ in physiological medium (containing 5 mM K+), though, in fact, there was an approximately 20% decrease in the presence of 100 microM of drug. Nifedipine, however, did cause a significant blockade of the entry of 45Ca in medium containing 10 or 15 mM K+, demonstrating that L-type channels on synaptosomes were operational under depolarising conditions. Under these depolarising conditions, there was an additive inhibitory effect on entry of 45Ca into synaptosomes when U50488H (1 microM) and nifedipine (1 microM) were incubated together. Treatment of synaptosomes with omega-conotoxin (omega-CgTx, 0.5 microM) resulted in a 35% reduction in the uptake of 45Ca. omega-Conotoxin (0.5 microM) or naloxone (20 microM) abolished the inhibitory effect of U50488H on the uptake of 45Ca, but naloxone did not alter the blockade of L-type Ca2+ channels, caused by nifedipine. In conclusion, the data demonstrate that under depolarising conditions, there are functional L-type calcium channels on nerve endings in the CNS.(ABSTRACT TRUNCATED AT 250 WORDS)

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗
PubMed2026

ARX mutation-associated interneuron defects provide insights into mechanisms underlying developmental epilepsies.

Cortical interneuron (cIN) dysfunction is associated with various neurodevelopmental and neurological disorders, including developmental epilepsies, autism spectrum disorders and intellectual disabilities. Mutations in ARX (aristaless-related homeobox) are linked to these conditions, with or without accompanying structural brain anomalies. We previously demonstrated that the loss of Arx in the mouse ganglionic eminence, the birthplace of cINs, is associated with seizures, whereas its loss in cortical excitatory neuron progenitor cells results in structural anomalies but no seizures. To elucidate the pathophysiological role of ARX in cINs and its relationship to seizure phenotype, Arx conditional mutant mouse lines were investigated using Gad2- and Nkx2.1-Cre drivers to target distinct populations in the cIN lineage. Our data demonstrate that ARX abrogation results in defects in cIN density and distribution, as well as perinatal lethality. In these mice, we observed defects in cell cycle exit, a biased loss of the marginal zone migration stream of cINs, shifts in cell fate from caudal ganglionic eminence to medial ganglionic eminence identity, and a reduced number of parvalbumin⁺ and somatostatin⁺ cINs, with parvalbumin⁺ cINs being more severely affected. Single-cell RNA sequencing combined with chromatin immunoprecipitation and sequencing revealed that ARX regulates key processes involved in cell cycle progression, cIN subtype differentiation and cIN migration. Investigation of one downregulated target gene, Lmo1, uncovered a potential mechanism by which ARX regulates the number and distribution of cINs in the cortex. Cortical slice cultures demonstrate that LMO1 inhibits cIN migration by repressing Cxcr4 expression, which encodes a key receptor involved in cortical guidance. These data indicate that ARX positively regulates cIN migration by derepressing LMO1's repressive role. Consistent with our mouse model, we observed a significant loss of parvalbumin+ and somatostatin+ cINs in the brain of a patient carrying a pathogenic variant of ARX, who was diagnosed with developmental epileptic encephalopathy. Together, our data provide novel insights into how ARX and its target genes regulate cIN development and migration and into the pathogenic mechanisms underlying a spectrum of neurodevelopmental disorders linked to loss of ARX.

Animals↗
PubMed1977

Operative techniques for management of lesions involving the dural venous sinuses.

The basic principles of vascular surgery, adequate exposure, proximal and distal control of hemorrhage, and meticulous approximation of endothelial surfaces should be adhered to in the management of lesions of the dural venous sinuses. Modification of conventional vascular techniques must be made since the major dural venous sinuses are essentially non collapsible and non mobilizable because of the entry of cortical veins at frequent intervals along their course. These problems can be solved by occlusion of the proximal and distal segments of the sinus from within the lumen and by use of a shunt consisting of a siliconized non-collapsible tube with an inflatable balloon cuff at each end. Saphenous vein autografts are used if primary repair is impossible because of loss of tissue. Using these techniques, a patency rate of 91% and a mortality rate of 9% were achieved in eleven cases involving the posterior sagittal and transverse sinuses.

Brain Injuries↗
PubMed1991

Feedback inhibition of cyclic adenosine monophosphate-stimulated Na+ transport in the rabbit cortical collecting duct via Na(+)-dependent basolateral Ca++ entry.

Arginine vasopressin (AVP) transiently stimulates Na+ transport in the rabbit cortical collecting duct (CCD). However, the sustained effect of both AVP and its putative second messenger, cyclic adenosine monophosphate (cAMP), on Na+ transport in the rabbit CCD is inhibitory. Because maneuvers that increase [Ca++]i inhibit Na+ transport, the effects of AVP and cell-permeable cAMP analogues, on [Ca++]i were investigated in fura-2-loaded in vitro microperfused rabbit CCDs. Low-dose AVP (23-230 pM) selectively stimulated Ca++ influx, whereas 23 nM AVP additionally released calcium from intracellular stores. 8-chlorophenylthio-cAMP (8CPTcAMP) and 8-bromo-cAMP (8-Br-cAMP) also increased CCD [Ca++]i. The 8CPTcAMP-stimulated [Ca++]i increase was totally dependent on basolateral [Ca++]. In the absence of cAMP, peritubular Na+ removal produced a marked increase in [Ca++]i, which was also dependent on bath [Ca++], suggesting the existence of basolateral Na+/Ca++ exchange. Luminal Na+ removal in the absence of cAMP did not alter CCD [Ca++]i, but it completely blocked the cAMP-stimulated [Ca++]i increase. Thus the cAMP-dependent Ca++ increase is totally dependent on both luminal Na+ and basolateral Ca++, suggesting the [Ca++]i increase is secondary to cAMP effects on luminal Na+ entry and its coupling to basolateral Na+/Ca++ exchange. 8CPTcAMP inhibits lumen-to-bath 22Na flux [JNa(l-b)] in CCDs bathed in a normal Ca++ bath (2.4 mM). However, when bath Ca++ was lowered to 100 nM, a maneuver that also blocks the 8CPTcAMP [Ca++]i increase, 8CPTcAMP stimulated, rather than inhibited JNa(l-b). These results suggest that cAMP formation initially stimulates CCD Na+ transport, and that increased apical Na+ entry secondarily activates basolateral Ca++ entry. The cAMP-dependent [Ca++]i increase leads to inhibition Na+ transport in the rabbit CCD.

Animals↗
PubMed1977

Fertilization of immature frog eggs: cleavage and development following subsequent activation.

Frog eggs are normally fertilized after reaching metaphase II. When eggs are inseminated prior to that, several sperm enter, but entry does not activate the egg. When such inseminated, immature eggs were maintained until they became mature and then were artificially activated, the eggs began to cleave. The cleavage furrows were irregular and often multiple, but the eggs developed to blastulae or partial blastulae. About 2 leads to 5% of the eggs developed to tadpoles. Typical asters were not associated with the entering sperm; rather, asters appeared only after activation. The sperm nucleus often formed chromosomes which were attached to small spindles. It is clear that sperm which remain for a time in unactivated egg cytoplasm, retain their ability to promote cleavage and development. Aster formation required not only sperm centrioles but also activated egg cytoplasm. Sperm which entered either near the equator or in the animal half of mature eggs usually produced normal cleavage furrows. Sperm which entered the animal half of immature eggs produced multiple animal half furrows when the egg was subsequently activated. In contrast, sperm which entered near the equator of immature eggs often failed to induce furrowing on subsequent activation or produced unusual equatorial furrows. The difference in the type of furrow between eggs inseminated in the animal half or at the equator is interpreted as a consequence of dissociating sperm entry from the cortical contraction which occurs in activation.

Animals↗
PubMed1991

Quantitative microfocal radiographic assessment of disease and progression in osteoarthritis of the hand.

Macroradiographic examination of the wrists and hands of 32 patients with osteoarthritis (OA) over an 18 month period showed that, compared with healthy control subjects, 44% of the patients had significant joint space narrowing at entry, which increased to 65%. Subchondral cortical thickness was greater in all patients at entry and increased with time. Osteophytes and juxtaarticular radiolucencies were present in all patients at study entry; by the end, osteophytes had increased in number and area, and juxtaarticular radiolucencies in area only. We conclude that in OA of the hand, bony changes have progressed significantly before joint space narrowing.

Aged↗
PubMed1990

Sodium entry routes in principal and intercalated cells of the isolated perfused cortical collecting duct.

Transmembrane sodium transport pathways were studied in principal and intercalated cells of the isolated perfused rabbit cortical collecting duct. Intracellular electrolyte concentrations in individual collecting duct cells were measured by electron microprobe analysis during blockage of basolateral Na-K-ATPase by ouabain and simultaneous inhibition of sodium entry across the apical and/or basolateral cell membrane. In principal cells the ouabain-induced rise in cell sodium concentration could only partially be blocked by amiloride (10(-4) mol/l) in the perfusion fluid. Amiloride (10(-3) mol/l) added to the bathing solution produced a further, significant reduction of sodium influx. In principal cells the ouabain-induced increase in sodium concentration was completely prevented by amiloride in the perfusion solution in combination with omission of sodium from the peritubular bathing solution. In intercalated cells ouabain caused a less pronounced increase in sodium concentration than in principal cells. Neither amiloride in the perfusate, nor amiloride in both bathing and perfusion solution, significantly reduced the ouabain-induced rise in intercalated cell sodium concentration. These results indicate that in principal cells amiloride-sensitive sodium channels constitute the predominant pathway for sodium entry across the apical cell membrane. In addition, substantial amounts of sodium enter principal cells across the basolateral cell membrane, probably via Na-H exchange. Finally, the data suggest that in intercalated cells sodium channels and the Na-H exchange are sparse or even absent.

Amiloride↗
PubMed1979

Oocyte maturation: aberrant post-fusion responses of the rabbit primary oocyte to penetrating spermatozoa.

Primary oocytes cannot be fertilized normally; they begin to develop this capacity as meiosis resumes. To elucidate the changes involved in acquisition of their fertilizability, rabbit primary oocytes displaying a germinal vesicle (GV oocytes) were placed in Fallopian tubes inseminated previously with spermatozoa, recovered 2--5 h later and examined by light and electron microscopy. At least 4 aspects of GV oocyte/sperm interaction were abnormal. Although the vestments and oolemma seem normally receptive to spermatozoa, fusion with the oolemma of the primary oocyte did not elicit exocytosis of cortical granules, and consequently multiple entry of spermatozoa into the ooplasm was common. Secondly, the GV oocyte cortex failed to achieve a normal englufment of the anterior part of the sperm head. It sank into the ooplasm capped by only a small rostral vesicle or left the stable inner acrosomal membrane as a patch in the oolemma. Only rarely then was there significant dispersion of the sperm chromatin, and this remained surrounded by nuclear envelope. The persistence of this envelope constitutes a further aberrant feature, for it disappears immediately in secondary oocytes and was absent in primary oocytes in which germinal vesicle breakdown had occurred. The results are discussed with particular reference to current ideas about male pronucleus formation.

Animals↗
PubMed1992

Acquisition of signs from American sign language in hearing individuals following left hemisphere damage and aphasia.

Three severely aphasic hearing patients with no prior knowledge of sign language were able to acquire competency in aspects of American Sign Language (ASL) lexicon and finger spelling, in contrast to a near complete inability to speak the English counterparts of these visuo-gestural signs. Two patients with damage in left postero-lateral temporal and inferior parietal cortices mastered production and comprehension of single signs and short meaningful sign sequences, but the one patient with damage to virtually all left temporal cortices was less accurate in single sign processing and was unable to produce sequences of signs at all. These findings suggest that conceptual knowledge is represented independently of the auditory-vocal records for the corresponding lexical entries, and that left anterior temporal cortices outside of traditional "language areas" are part of the neural network which supports the linkage between conceptual knowledge and linguistic signs, especially as they are used in the sequenced activations required for production or comprehension of meaningful sentences.

Adult↗
PubMed1991

Effects of diltiazem on postischaemic renal cortical microcirculation in the pig.

Diltiazem--a calcium entry blocker--was tested in a porcine model under continuous chlormethiazole-pancuronium anaesthesia as protection against renal failure following 60 min of renal ischaemia. Fourteen pigs were randomly allocated to one experimental (diltiazem and ischaemia) and one control group (only ischaemia) (n = 7 in each). Diltiazem was administered as a continuous intravenous infusion started before the ischaemic insult. In two additional animals diltiazem was given but ischemia was not induced. The postischaemic renal cortical microcirculation was simultaneously investigated in four different regions in the left kidney during the first 4 h of reperfusion. Laser Doppler flowmetry (LDF) was performed in two different regions and measurement of tissue oxygenation was done in two other regions. In the two animals treated with diltiazem without ischaemia, only minor variations in central haemodynamic and renal microcirculatory parameters were evident. In the control group (ischaemia), superficial renal cortical blood flow (Qsrc) decreased from 49 +/- 11 (s.d.) arbitrary units at baseline to 24 +/- 4 arb. units 4 h after start of reperfusion (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Kidney Injury↗
PubMed1988

Cerebrovascular and cerebral effects of nimodipine--an update.

A survey is given on the vascular and neuronal effects of calcium antagonists under physiological and pathological conditions. Special emphasis is put on vasospasm caused by subarachnoid haemorrhage and on postischaemic cerebral hypoperfusion following different forms of cerebral ischaemia, and on the attempts to influence these phenomena pharmacologically. Regarding its neuronal effects it seems likely that nimodipine potently blocks calcium entry during pathological conditions like cerebral ischaemia and spreading cortical depression. Positive effects also have been seen during epileptic seizures and withdrawal syndromes, whereas calcium entry under normal physiological conditions does not appear to be affected. Possible clinical consequences are discussed.

Animals↗
PubMed1992

Danger zone of the acetabulum.

The danger zone of the acetabulum is defined by Marvin Tile as that part of the posterior wall and column at the mid-acetabulum lying above the ischial spine. Screws inserted in the danger zone are at risk of violating the hip joint. Unfortunately, this zone is frequently used in the fixation of posterior wall and column fractures. Cadaveric studies were performed analyzing 1-cm cross-sections through the acetabulum for the purpose of studying the anatomical configuration of the danger zone. The plane of the cross-section was perpendicular to the posterior column. Each cross-section had the medial boundary of the acetabulum projected onto the posterior column. The cross-sections were then assembled to form the original acetabulum. By analyzing the projections on the posterior column, the exact configuration of the danger zone was determined. Screws placed at the margin of the danger zone and directed perpendicular to the posterior column violated the hip joint. Through analysis of the cross-sections, safe anatomic pathways were developed for screw placement. Cortical screws (4.5 mm), placed at entry points of 2 cm and 3 cm medial to the lateral acetabular margin and angled medially 45 degrees and 15 degrees, respectively, did not violate the hip joint. The angulation was respective to the perpendicular to the posterior column. In this study, the average width of the posterior column at the mid-acetabular level was 4.8 cm. Computed tomography scan of the acetabulum yielded valuable information regarding screw placement in the posterior column.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetabulum↗
PubMed1989

Apparent viscosity and cortical tension of blood granulocytes determined by micropipet aspiration.

Continuous deformation and entry flow of single blood granulocytes into small caliber micropipets at various suction pressures have been studied to determine an apparent viscosity for the cell contents and to estimate the extent that dissipation in a cortical layer adjacent to the cell surface contributes to the total viscous flow resistance. Experiments were carried out with a wide range of pipet sizes (2.0-7.5 microns) and suction pressures (10(2)-10(4) dyn/cm2) to examine the details of the entry flow. The results show that the outer cortex of the cell maintains a small persistent tension of approximately 0.035 dyn/cm. The tension creates a threshold pressure below which the cell will not enter the pipet. The superficial plasma membrane of these cells appears to establish an upper limit to surface dilation which is reached after microscopic "ruffles" and "folds" have been pulled smooth. With aspiration of cells by small pipets (less than 2.7 microns), the limit to surface expansion was derived from the maximal extension of the cell into the pipet; final areas were measured to be 2.1 to 2.2 times the area of the initial spherical shape. For suctions in excess of a threshold, the response to constant pressure was continuous flow in proportion to excess pressure above the threshold with only a small nonlinearity over time until the cell completely entered the pipet (for pipet calibers greater than 2.7 microns). With a theoretical model introduced in a companion paper, (Yeung, A., and E. Evans., 1989, Biophys. J. 56:139-149) the entry flow response versus pipet size and suction pressure was analyzed to estimate the apparent viscosity of the cell interior and the ratio of cortical flow resistance to flow resistance from the cell interior. The apparent viscosity was found to depend strongly on temperature with values on the order of 2 x 10(3) poise at 23 degrees C, lower values of 1 x 10(3) poise at 37 degrees C, but extremely large values in excess of 10(4) poise below 10 degrees C. Because of scatter in cell response, it was not possible to accurately establish the characteristic ratio for flow resistance in the cortex to that inside the cell; however, the data showed that the cortex does not contribute significantly to the total flow resistance.

Granulocytes↗
PubMed1990

Alcohol exposure and undernutrition: effects on lipid metabolism and alcohol partitioning in rat brain regions in vitro.

The effects of maternal alcohol consumption and undernutrition on lipid metabolism and alcohol partitioning in brain cortical and stem slices of pups were studied under in vitro conditions. Alcohol administration along with a normal diet during gestation and lactation resulted in an increase in the synthesis of cholesterol in cortical and stem slices associated with decreased entry of alcohol. Phospholipid metabolism was not affected in the cortex, whereas the incorporation of [32P] was found to be altered in the brain stem, indicating regional differences with respect to alcohol effects. Undernutrition induced by feeding the mothers a low protein diet, on the other hand, decreased the incorporation of labelled precursors into lipids in cortex and stem. The changes in lipid metabolism observed in the high protein alcohol pups were not evident in the brain regions of undernourished pups exposed to alcohol and the partitioning of alcohol was not altered.

Acetates↗