Callosal window between prefrontal cortices: cognitive interaction to retrieve long-term memory.

A perceptual image can be recalled from memory without sensory stimulation. However, the neural origin of memory retrieval remains unsettled. To examine whether memory retrieval can be regulated by top-down processes originating from the prefrontal cortex, a visual associative memory task was introduced into the partial split-brain paradigm in monkeys. Long-term memory acquired through stimulus-stimulus association did not transfer via the anterior corpus callosum, a key part interconnecting prefrontal cortices. Nonetheless, when a visual cue was presented to one hemisphere, the anterior callosum could instruct the other hemisphere to retrieve the correct stimulus specified by the cue. Thus, although visual long-term memory is stored in the temporal cortex, memory retrieval is under the executive control of the prefrontal cortex.

Biochemical studies on abnormal erythrocyte membranes. Protein abnormality of erythrocyte membrane in biliary obstruction.

Biochemical studies on erythrocyte membranes from eleven obstructive jaundice patients (due to various disorders) have been undertaken, By scanning electron microscopic observation these erythrocytes were spur and target in appearance. The lipid composition showed a marked increase in both cholesterol and phosphatidylcholine. In addition to these changes, it was unexpectedly demonstrated by polyacrylamide gel electrophoresis in sodium dodecyl sulfate that a specific membrane protein component 4.2 was reduced or absent in all cases tested. This membrane protein abnormality was identical with that of hereditary spherocytosis erythrocyte membranes. It is of particular interest to note that after surgical relief of biliary obstruction in a typical case of common duct cholelithiasis, the disc electrophoretic pattern of erythrocyte membranes became normal and both lipid composition and red cell morphology returned to normal.

Studies of diacylglycerol cholinephosphotransferase and diacylglycerol ethanolaminephosphotransferase activities in Tetrahymena microsomes.

Microsomes isolated from Tetrahymena pyriformis synthesized phosphatidylcholine and phosphatidylethanolamine by CDPcholine: 1,2-diacylglycerol cholinephosphotransferase (EC 2.7.8.2) and CDPethanolamine: 1,2-diacylglycerol ethanolaminephosphotransferase (EC 2.7.8.1), utilizing ethanol-dispersed dioleoglycerol. Cholinephosphotransferase and ethanolaminephosphotransferase activities have similar dependences on MgCl2 and MnCl2, but the latter was more effective than the former for both enzyme activities. The V values for 1,2-dioleoylglycerol obtained at optimal conditions were 1.8 nmol/min per mg microsomal protein for cholinephosphotransferase and 0.6 nmol/min per mg microsomal protein for ethanolaminephosphotransferase. Both enzymes could not utilize 1,3-dioleoylglycerol or 1-oleoylglycerol as substrates. Cholinephosphotransferase had an apparent Km for CDPcholine of 11.7 microM with 1,2-dioleoylglycerol and was inhibited by CDPethanolamine competitively. On the other hand, ethanolaminephosphotransferase has an apparent Km for CDPethanolamine of 8 microM and CDPcholine was a noncompetitive inhibitor of ethanolaminephosphotransferase activity. Furthermore, despite the marked alteration of phospholipid composition occurring during the temperature acclimation of Tetrahymena cells, both enzyme activities showed similar dependences on growth and incubation temperatures. This may imply that the final step of de novo synthesis of two major phospholipids does not participate in the thermally induced modification of the profile of phospholipid polar head group in membranes.

Noninvasive study of the presystolic component of the first heart sound in mitral stenosis.

Echophonocardiography and pulsed Doppler echocardiography were performed in 30 patients with mitral stenosis (19 with atrial fibrillation and 11 with sinus rhythm) to investigate the genesis of the presystolic component or small apical vibrations preceding the first heart sound in mitral stenosis. In 27 patients, mitral valve closure preceded or coincided with tricuspid valve closure regardless of the preceding RR interval. Of three patients whose tricuspid valve closed prematurely, two had a prolonged PR interval. The soft apical vibrations, which were recorded during the final rapid closing motion of the mitral valve echogram (B-C slope), began with the upstroke of the apexcardiogram. During this event the pulsed Doppler echocardiogram revealed a deceleration in the velocity of mitral inflow. In two exceptional patients with a prolonged PR interval, this apical sound was separated from a presystolic rumble that occurred during an accelerated phase of mitral inflow or at the A wave of mitral valve echograms. In conclusion, the tricuspid valve is not a factor contributing to the genesis of the small apical vibrations preceding the first heart sound in mitral stenosis. These vibrations are caused by acceleration of left ventricular contraction and deceleration of mitral inflow in the presence of a stenotic valve.

Comparison of artifacts on coronal reformation and axial CT pulmonary angiography images using single-detector and 4- and 8-detector multidetector-row helical CT scanners.

RATIONALE AND OBJECTIVES: The aim of this study is to compare the degree of stair-step artifact on coronal reformation computed tomographic (CT) pulmonary angiography images obtained using single-detector helical CT (SDCT), four-detector (4-MDCT), and eight-detector multidetector-row CT (8-MDCT) and compare the degree of motion artifact on the corresponding axial CT images. MATERIALS AND METHODS: Three groups of consecutive patients imaged by means of CT angiography for suspected pulmonary embolus were retrospectively identified by using CT records at our institution: (1) group A (n = 38), SDCT; (2) group B (n = 36), 4-MDCT; and (3) group C (n = 74), 8-MDCT. For each case, coronal multiplanar volume reformation maximal intensity projection images were created by using a standard technique. All images were reviewed in a randomized fashion by two thoracic radiologists who were blinded to the type of CT scanner. Stair-step artifact of pulmonary arteries on coronal reformation images was graded by consensus agreement using a four-point scale (0 = no artifact to 3 = severe artifact). Axial images were assessed for six parameters of motion artifact. The sum of these grades resulted in a total motion score, with a potential range of 0 (no motion) to 12 (severe motion). Statistical analysis was performed using the Mann-Whitney test. RESULTS: Stair-step artifacts were significantly higher for SDCT (mean, 2.9; median, 3) compared with 4-MDCT (mean, 2.2; median, 2; P < .0001) and 8-MDCT (mean, 1.5; median, 1; P < .0001). Total motion scores were significantly higher for SDCT (mean, 9.3) compared with 4-MDCT (mean, 8.4; P = .03) and 8-MDCT (mean, 6.8; P < .0001). CONCLUSION: Stair-step artifacts are significantly higher with SDCT compared with MDCT. For MDCT, eight-detector scanners produce images with significantly less artifact than four-detector scanners.

Interactions between clarithromycin and digoxin in patients with end-stage renal disease.

OBJECTIVE: To report a significant increase in the serum levels of digoxin associated with the use of clarithromycin in six patients undergoing renal replacement therapy. CASE SUMMARY: All six patients were males with end-stage renal disease and in need of renal replacement therapy. Four patients were anuric. The mean age was 78.8 +/- 5.8 (66-83) years. All patients except one, who was treated by hemofiltration, were treated by hemodialysis. All patients except one, who had been treated with metildigoxin (0.35 mg/week), were also taking digoxin (0.375 mg/week). Clarithromycin was administered at a dose of 200-400 mg/day for the treatment of bronchitis in all patients. The concomitant administration of clarithromycin increased serum digoxin levels from 1.8-4.0-fold in all cases. In two of six cases, a high probability of digoxin intoxication and suspicion of digoxin intoxication was evident. In three of six cases, serum digoxin levels increased within 12 days after the co-administration of clarithromycin, while in the other three cases, serum digoxin levels were increased 53-190 days after the administration of clarithromycin. CONCLUSION: The simultaneous administration of clarithromycin caused an increase in digoxin levels in six patients undergoing renal replacement therapy. The increase in the serum digoxin can be attributed to the inhibition of P-glycoprotein in the intestine and/or bile capillary rather than the kidney by clarithromycin since renal function was dramatically impaired, and four of the patients were anuric. The issue of why serum digoxin levels were increased so late in three patients undergoing renal replacement is unclear. However, this interaction seemed to be clinically significant even in ESRD patients, whose renal function was highly impaired. The simultaneous use of digoxin and clarithromycin should be avoided even in patients undergoing renal replacement therapy whose renal function is impaired, since digoxin levels may increase unexpectedly.

Neural mechanisms of memory retrieval: role of the prefrontal cortex.

In the primate brain, long-term memory is stored in the neocortical association area which is also engaged in sensory perception. The coded representation of memory is retrieved via interactions of hierarchically different cortical areas along bottom-up and top-down anatomical connections. The functional significance of the fronto-cortical top-down neuronal projections has been relevantly assessed in a new experimental paradigm using posterior-split-brain monkeys. When the splenium of the corpus callosum and the anterior commissure were selectively split, the bottom-up visual signal originating from the unilateral striate cortex could not reach the contralateral visual cortical areas. In this preparation, long-term memory acquired through visual stimulus-stimulus association learning was prevented from transferring across hemispheres. Nonetheless, following the presentation of a visual cue to one hemisphere, the prefrontal cortex could instruct the contralateral hemisphere to retrieve the correct stimulus specified by the cue. These results support the hypothesis that the prefrontal cortex can regulate memory recall in the absence of bottom-up sensory input. In humans, functional neuroimaging studies have revealed activation of a distributed neural network, including the prefrontal cortex, during memory retrieval tasks. Thus, the prefrontal cortex is consistently involved in retrieval of long-term memory in primates.

Cytotoxic antibody against trophoblast and lymphocytes present in pregnancy with intrauterine fetal growth retardation and its relation to anti-phospholipid antibody.

To elucidate immunological mechanisms involved in the genesis of intra-uterine fetal growth retardation (IUGR), an in vitro cytotoxicity assay against normal trophoblast and lymphocytes was performed. The data demonstrated the existence of cytotoxic antibody directed against trophoblast exclusively in the IgG fraction of the sera of 9 out of 15 mothers with IUGR, but in none of the sera from normal pregnant women. This antibody showed differential reactivity patterns that may be indicative women. This antibody showed differential reactivity patterns that may be trophoblast in common. Out of 9 IUGR mothers with this cytotoxic antibody, in 6 cases (66.7%) chronic villitis was evident upon microscopic examination of the placenta, the frequency being significantly higher than that in IUGR mothers without cytotoxicity or in control mothers (P less than 0.02). It is suggested that in situ inflammatory change triggered by this antibody might lead to IUGR through chronic villitis. This antibody showed cross-reactivity with anti-negatively charged phospholipid antibody, as confirmed by an absorption experiment, indicating that the trophoblast antigenic stimuli in pregnancy can induce the production of various autoantibodies including anti-phospholipid antibodies. These results are of interest in relation to the pathogenesis of autoimmune diseases.

Influence of immunotherapy on the cellular immunity of unexplained recurrent aborters.

Changes in lymphocyte subsets in whole blood were analyzed sequentially by flow cytometry with an automated leukocyte differential system in 15 patients with unexplained recurrent spontaneous abortions, each of whom underwent vaccination(s) with her husband's lymphocytes. Mitogen responses of peripheral blood lymphocytes (PBL) were also examined in these patients. The reactivity of PBL against mitogens revealed no significant change in each patient before and after vaccination(s) with her husband's lymphocytes. The CD4:8 ratio was observed to decrease significantly during 22 and 28 days after the first vaccination with a significant increase in the percentage of T suppressor-cytotoxic (CD8) cells. This change was also observed after the second vaccination. The percentages of other subsets did not change significantly after vaccination(s). In 11 patients out of 15, the pregnancy continued successfully and correlated with a predominance of Ts/c (CD8) over TH/I (CD4) cells in the first trimester. These changes in lymphocyte subsets may indicate the induction of immune enhancing mechanisms and it is suggested that continuation of the predominance of Ts/c cells induced by immunotherapy might be important for the successful maintenance of pregnancy.

Evaluation of threatened preterm delivery by transvaginal ultrasonographic measurement of cervical length.

OBJECTIVE: To establish a nomogram for the length of the uterocervical canal and to determine whether this can be used to predict preterm delivery. METHODS: Cervical length was measured by transvaginal ultrasonography in 32 women (21 primigravid, 11 multigravid) with threatened preterm delivery, and in 177 normal singleton pregnancies between 18-37 weeks' gestation. Regression analysis was used to create the nomogram. Student t test was used to compare the groups. RESULTS: A linear relationship was found between cervical length and gestational age (r = -0.4, P < .001). Comparison of cervical length on admission in the patients with threatened preterm delivery showed that 11 preterm deliveries occurred in women who had a mean cervical length of 23.2 mm (range 17-29), whereas 21 term deliveries occurred in women with a mean cervical length of 31.7 mm (range 21-42). The difference was significant (P < .001). A cervical length of less than 20 mm on admission had a positive predictive value of 100%. These patients had preterm delivery despite tocolytic therapy during hospitalization. CONCLUSION: The risk of preterm delivery is high in women whose cervical length on admission is less than 30 mm, and strict management is required for those with a cervical length of less than 20 mm.

Studies on the cytogenetic and endocrinologic background of spontaneous abortion.

OBJECTIVE: To determine whether chronic menstrual irregularity with elevated LH levels has a role in spontaneous abortion. DESIGN: In 41 consecutively examined women with spontaneous abortions occurring within 11 complete gestational weeks, fetal chromosomal analyses were performed. The differences of endocrinologic background in relation to the result of fetal chromosomal analyses were investigated. MAIN OUTCOME MEASURES: Endocrinologic profiles, including menstrual history, basal hormone levels (LH, FSH, and PRL), ovarian morphology on ultrasound, and fetal chromosomal karyotypes. RESULTS: The women with normal fetal karyotypes compared with those with abnormal fetal karyotypes showed higher frequency of menstrual irregularity (47.1% versus 8.3%), elevated basal LH levels (7.42 +/- 5.12 versus 4.41 +/- 1.39 mIU/mL; conversion factor to SI unit, 1.00), and higher frequency of polycystic ovary (41.2% versus 8.3%). CONCLUSION: Elevated LH-polycystic ovary may be involved in the genesis of spontaneous abortions that are not explainable by fetal chromosomal abnormality.

Chromosome analysis of aborted conceptuses of recurrent aborters positive for anticardiolipin antibody.

OBJECTIVE: To elucidate the relationship between anticardiolipin antibody and recurrent abortion. DESIGN: Prospective clinical study. SETTING: Institutional practice in which patients with recurrent abortion were registered at the outpatient clinic for infertility of Niigata University Hospital. PATIENT(S): Five hundred sixty-one patients with recurrent abortions and 148 patients who were not recurrent aborters and who had experienced sporadic abortion. INTERVENTION(S): Aborted conceptuses for chromosome analyses were collected from the patients. MAIN OUTCOME MEASURE(S): The positive rate of anticardiolipin antibody was assessed in patients with recurrent abortion. Chromosome analyses of aborted conceptuses were performed in 10 patients with positive anticardiolipin antibody who had experienced another pregnancy that resulted in repeated abortion. Similar analyses of aborted conceptuses from 148 sporadic early abortions (controls) were performed. RESULT(S): The incidence of chromosome abnormalities in anticardiolipin antibody-positive recurrent aborters was 20.0% (2 of 10 cases), which was significantly lower than that of patients with sporadic abortion (60.1%, 89 of 148 cases). CONCLUSION(S): The low incidence of chromosome abnormalities in aborted conceptuses of patients with positive anticardiolipin antibody suggests that this antibody is strongly implicated in the genesis of recurrent abortions.

Immunotherapy with paternal lymphocytes preceding in vitro fertilization-embryo transfer for patients with repeated failure of embryo transfer.

Immunotherapy with paternal lymphocytes for unexplained recurrent aborters was applied, preceding IVF-ET, for infertile women with repeated failure of ET. In one patient showing close histocompatibility with the husband, the subsequent new IVF-ET was successful under positive MLR-blocking antibody induced by immunotherapy.

A new lymphocyte serotyping using cytotoxic antibodies from secondary recurrent aborters and its application in cases of recurrent abortion and infertility.

Using nonanti-human lymphocyte antigen (HLA) lymphocytotoxic antibodies derived from women with an abnormal pregnancy history including secondary recurrent abortion, a new series of serotyping was performed on lymphocytes from 37 couples (74 individuals), and the compatibility between the couples shown by the typing was investigated. The data demonstrated that both couples with primary recurrent abortion and infertile couples with repeated failure of embryo transfers after in vitro fertilization showed significantly close reaction patterns between partners than normal child-bearing couples by principal component factor analysis. It was concluded that this serotyping provides useful information on histocompatibility in the field of pregnancy immunology and that some cases of infertility because of implantation failure, as well as primary recurrent abortion, might be caused by underlying immunogenetical problems.

Prednisolone plus low-dose aspirin improves the implantation rate in women with autoimmune conditions who are undergoing in vitro fertilization.

OBJECTIVE: To evaluate the effect of prednisolone plus low-dose aspirin (PSL/LDA) in women with autoimmune conditions who were enrolled in an IVF-ET program. DESIGN: A retrospective clinical study. SETTING: In vitro fertilization unit, Niigata University Hospital, Niigata, Japan. PATIENT(S): Three hundred seven women who underwent IVF-ET between January 1996 and December 1997. INTERVENTION(S): Prednisolone (10 mg/d) and aspirin (81 mg/d) were administered to the women with autoantibodies who chose to participate. MAIN OUTCOME MEASURE(S): Pregnancy and implantation rates with IVF-ET. RESULT(S): Women undergoing IVF who had positive antinuclear antibodies, with or without antiphospholipid antibodies, had significantly lower pregnancy and implantation rates than did women without autoantibodies (14.8% versus 21.7% and 6.8% versus 10.4%, respectively). The administration of PSL/LDA to women with antinuclear antibodies significantly improved the outcome of IVF-ET (40.6% pregnancy rate and 20.3% implantation rate). CONCLUSION(S): A high proportion of women who are undergoing IVF-ET have autoantibodies, which are associated with poor IVF outcomes. The administration of PSL/LDA to these women may improve their implantation rate.

Effect of troglitazone on endocrine and ovulatory performance in women with insulin resistance-related polycystic ovary syndrome.

OBJECTIVE: To investigate the effect of troglitazone, a new antidiabetic agent that improves insulin resistance, on endocrine, metabolic, and ovulatory performance in women with insulin resistance-related polycystic ovary syndrome (PCOS). DESIGN: Prospective clinical study. SETTING: Infertility outpatient clinic, Niigata University Hospital, Niigata, Japan. PATIENT(S): Thirteen women with PCOS and insulin resistance. INTERVENTION(S): Troglitazone (400 mg/d) was administered for 12 weeks. MAIN OUTCOME MEASURE(S): Insulin and other hormone (gonadotropins, androgens) levels; various parameters relating to glucose and lipid metabolism before, during, and after troglitazone administration; and ovulation rate. RESULT(S): The mean (+/-SD) fasting insulin concentration was significantly reduced, from 18.3+/-8.9 to 10.5+/-7.1 microU/mL. The LH level was reduced from 9.7+/-3.4 to 4.8+/-3.9 mIU/mL and the testosterone level was reduced from 0.9+/-0.5 to 0.5+/-0.3 ng/mL in accordance. Atherosclerotic lipid levels also were normalized. Before troglitazone administration, the ovulation rate during clomiphene citrate therapy was 34.9% per cycle (15/43). This increased significantly to 72.7% (8/11) during troglitazone coadministration. Further, an ovulation rate of 42.3% (11/26) was achieved with troglitazone alone. CONCLUSION(S): In women with PCOS and insulin resistance, the reduction of hyperinsulinemia that is produced by troglitazone improves the hyperandrogenism that characterizes PCOS, restoring ovulation.

Establishment of two distinct anti-cardiolipin antibody-producing cell lines from the same individual by Epstein-Barr virus transformation.

Two anti-cardiolipin antibody (ACA)-producing cell lines were established, using Epstein-Barr virus transformation followed by a repeated cluster-picking from the same individual with antiphospholipid syndrome who had a history of 8 consecutive fetal losses and deep venous thrombosis. Characterization of the two ACAs derived from these cell lines revealed that one (Ab-019, subclass IgM, kappa) reacted exclusively with cardiolipin and showed strong lupus anticoagulant activity, while the other (Ab-226, subclass IgM, lambda) reacted with negatively charged phospholipids such as phosphatidylserine and phosphatidylglycerol, as well as cardiolipin. Furthermore, Ab-226 showed reactivity with human umbilical vein endothelial cells whereas Ab-019 did not. It is suggested that ACA is heterogeneous even in the same individual, and that reactivity against negatively charged phospholipids corresponds to reactivity against endothelial cell.

Relationship between mitral regurgitation and left ventricular outflow obstruction in hypertrophic cardiomyopathy.

To clarify the relationship between mitral regurgitation and left ventricular outflow obstruction, Doppler and two-dimensional echocardiographic studies were performed in 62 patients with hypertrophic cardiomyopathy (22 with and 40 without obstruction caused by mitral systolic anterior motion with septal contact). Pulsed Doppler echocardiography with color Doppler flow imaging demostrated that in 20 of the 22 patients with obstruction, mitral regurgitation occurred mainly during midsystole from the onset to the end of mitral-septal contact. Such midsystolic mitral regurgitation was not observed in patients without obstruction, except in three of 25 patients with mild mitral systolic anterior motion without septal contact. Furthermore, that regurgitation developed or disappeared together with the obstruction during follow-up periods or pharmacologic interventions. Two-dimensional echocardiography showed that in 21 of the 22 patients with obstruction, a distal residual portion of the "anterior" mitral leaflet moved anteriorly in early systole and protruded into the outflow tract during midsystole to cause the obstruction. In the other patient with obstruction, who had only early systolic mitral regurgitation, a distal residual "posterior" leaflet moved similary. These results may indicate that the midsystolic mitral regurgitation is hydrodynamically induced by the midsystolic pressure gradient across the protruding distal residual anterior mitral leaflet.

Sensitive enzyme immunoassay for the measurement of platelet factor 4 in blood plasma.

A sandwich enzyme immunoassay method for the measurement of platelet factor 4 (PF4) was developed with the use of polystyrene balls with immobilized antibody F(ab')2 fragments and the same antibody Fab' fragments labeled with beta-D-galactosidase from E. coli. The measurable range was 30 pg to 3 ng of PF4 per tube. Within-run and between-run coefficients of variation were less than 10%. The results obtained with the enzyme immunoassay correlated well with those of a radioimmunoassay (r = 0.952, slope = 0.954, gamma-intercept = 2.43 ng/ml). Platelets contained large amounts of PF4 (7.21 +/- 1.97 ng/10(6) cells or 2.51 +/- 1.13 ng/mg protein), whereas the PF4 levels in red blood cells and lymphocytes were negligible, confirming the specific localization of PF4 in platelets. The applicability of the immunoassay method was tested to determine the in vitro release of PF4 during preparation and storage of platelet concentrates.

Mechanism for lipid abnormalities of erythrocyte membranes in biliary obstruction: lecithin content and its fatty acyl composition.

The lipid compositions of erythrocyte membranes, plasma and bile of 16 patients with biliary obstruction were analysed to obtain information regarding the origin of excess lecithin which is usually found in the erythrocyte membranes in obstructive jaundice. Phospholipids and free cholesterol were found to be increased proportionally to the degree of biliary obstruction with an elevation in the free cholesterol/phospholipid ratio in the red cell membranes. The increase in phospholipid content is primarily due to lecithin. There was a highly significant alteration in the fatty acid composition of lecithin of erythrocyte membranes, plasma and bile from patients with severe jaundice. Red cell membrane lecithin amounted to more than 40% of the total phospholipid in these patients. Interestingly, the fatty acid composition of lecithin showed a similar pattern in erythrocyte membranes, plasma and bile. In addition, the fatty acyl chain composition of lecithin in lipoprotein-X was very similar to that of the red cell membrane. Freeze-fracture electron microscopy showed an alteration in membrane morphology and a reduced number of membrane-associated particles in the fractured faces. From these findings, we suggest that the lecithin of lipoprotein-X is derived from abnormal bile lecithin, which is incorporated into erythrocyte membranes by fusion with lipoprotein-X. On the other hand, the fatty acid composition of bile lecithin from patients with mild jaundice, whose erythrocyte membrane lecithin amounted to less than 31% of total phospholipid, was not different from that of normal individuals. However, in sharp contrast to the bile content, the fatty acid composition of erythrocyte membranes and plasma in these same patients showed a similar but small change compared to that of patients with severe biliary obstruction. The red cells of patients with mild jaundice were almost normal, biconcave disc-shaped, as observed by scanning electron microscopy and no abnormalities in the distribution or number of membrane particles were detected by freeze-fracturing. We propose that the abnormal lecithin content of erythrocyte membranes in patients with mild jaundice can be explained by the gradual exchange of lecithin between red blood cells and plasma lipoprotein.