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The optimal timing for electrical cardioversion (ECV) in acute decompensated heart failure (ADHF) with atrial arrhythmias (AAs) is unknown. Here, we retrospectively evaluated the impact of ECV timing on SR maintenance, hospitalization duration, and cardiac function in patients with ADHF and AAs. Between October 2017 and December 2022, ECV was attempted in 73 patients (62 with atrial fibrillation and 11 with atrial flutter). Patients were classified into two groups based on the median number of days from hospitalization to ECV, as follows: early ECV (within 8 days, n = 38) and delayed ECV (9 days or more, n = 35). The primary endpoint was very short-term and short-term ECV failure (unsuccessful cardioversion and AA recurrence during hospitalization and within one month after ECV). Secondary endpoints included (1) acute ECV success, (2) ECVs attempted, (3) periprocedural complications, (4) transthoracic echocardiographic parameter changes within two months following successful ECV, and (5) hospitalization duration. ECV successfully restored SR in 62 of 73 patients (85%), with 10 (14%) requiring multiple ECV attempts (≥ 3), and periprocedural complications occurring in six (8%). Very short-term and short-term ECV failure occurred without between-group differences (51% vs. 63%, P = 0.87 and 61% vs. 72%, P = 0.43, respectively). Among 37 patients who underwent echocardiography before and after ECV success, the left ventricular ejection fraction (LVEF) significantly increased (38% [31-52] to 51% [39-63], P = 0.008) between admission and follow-up. Additionally, hospital stay length was shorter in the early ECV group than in the delayed ECV group (14 days [12-21] vs. 17 days [15-26], P < 0.001). Hospital stay duration was also correlated with days from admission to ECV (Spearman's ρ = 0.47, P < 0.001). In clinical practice, early ECV was associated with a shortened hospitalization duration and significantly increased LVEF in patients with ADHF and AAs., (© 2024. Springer Nature Japan KK, part of Springer Nature.)

The clinical course of follicular lymphoma (FL) is thought to be influenced by the infiltrating immune cells in the tumor microenvironment. Focusing on the distribution patterns of T cells may be a promising approach to estimate the prognosis of FL, especially histological transformation. This study was a retrospectively cohort study in the relationship between the pathological distribution pattern of T cells in the tumor microenvironment and clinical course of FL. One hundred twenty-eight patients with FL initially diagnosed at the University of Tokyo Hospital from January 2008 to January 2017 were evaluated. We classified each patient's specimen at initial diagnosis by the distribution pattern of tumor infiltrating CD3-positive cells, intra-follicle focal (IFF), intra-follicle diffuse (IFD), extra-follicle marginal (EFM), and extra-follicle diffuse (EFD). We analyzed the distribution pattern's correlation with other prognostic factors including overall survival (OS), progression free survival (PFS), and transformation. Among 128 cases, 81 had evaluable pathological specimen. Based on our criteria, in the intra-follicle,17 cases (21%) were classified as IFF. Sixty-four cases (79%) were classified as IFD. In the extra follicle, 25 cases (31%) were classified as EFM. Fifty-six cases (69%) were classified as EFD. There was significant difference in risk of transformation between the EFM and EFD around extra-follicle area in the adjusted model (p < 0.05). Also, cases with IFF and EFM had significantly higher risk of transformation compared to cases with other T cell distribution patterns (p < 0.01). We proposed a new classification of CD3-positive T cell distribution patterns around the follicle lesions in FL and demonstrated its clinical significance., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Some patients with pacemakers present with first-degree atrioventricular (AV) block. To avoid right ventricular (RV) pacing, preserving intrinsic AV conduction as much as possible is recommended. However, there is no clear cutoff AV interval to determine whether intrinsic AV conduction should be preserved or RV pacing should be delivered. This study aimed to compare a pacing mode-preserving, intrinsic AV conduction with the DDD mode delivering RV pacing in terms of echocardiographic parameters in patients with first-degree AV block and to investigate whether RV pacing induces heart failure (HF). Stroke volume (SV) was measured to determine the optimal AV delay with the intrinsic AV conduction rhythm and the DDD pacing delivering RV pacing. Echocardiographic evaluation was performed for 6-month follow-up period. Seventeen patients were studied. At baseline, mean intrinsic PQ interval was 250 ± 40 ms. SV was greater with RV pacing with optimal AV delay of 160 ms than with intrinsic AV conduction rhythm in all patients. Therefore, pacemakers were set to the DDD to deliver RV pacing. During follow-up, seven patients developed HF. Mean baseline E/E' ratio in patients who developed HF (HF group) during RV pacing was higher than in patients without HF (non = HF group; 17.9 ± 8 versus 11.5 ± 2, P = 0.018) Even within HF group patients without a high baseline E/E' ratio, it increased with RV pacing (22.2 ± 6 versus 11.6 ± 2; P < 0.001). In patients with pacemaker and first-degree AV block, RV pacing with the optimal AV delay of 160 ms increased SV. However, the risk of HF may be increased with RV pacing if the E/E' ratio is > 15 during intrinsic AV conduction or RV pacing. RV pacing should be avoided in patients with high E/E' ratio under intrinsic AV conduction or RV pacing., (© 2022. The Author(s).)

The relationship between the socioeconomic status, including the health insurance status, and prognosis of heart failure (HF) has been recognized as an important concept for stratifying the risk in HF patients and is gaining increasing attention worldwide even in countries with a universal healthcare system. However, the impact of the Japanese health insurance status on outcomes among patients admitted for acute HF has not been fully clarified. We enrolled 771 patients admitted for acute HF between January 2018 and December 2019 and collected data on the in-hospital mortality, length of the hospital stay, and cardiac events, defined as cardiovascular death and readmission for HF within 1 year after discharge. Patients were divided into two groups according to their insurance status, i.e., public assistance (n = 87) vs. other insurance (n = 684). The public assistance group was significantly younger and had a higher rate of diabetes, smoking, ischemic and hypertensive heart disease, and low estimated glomerular filtration rate (all P < 0.05). Pharmacological/invasive heart failure therapy, in-hospital mortality, and the 90-day cardiac event rate after discharge did not differ between the groups. However, the public assistance group had a significantly higher 1-year cardiac event rate than the other insurance groups (P = 0.025). After adjusting for covariates, public assistance was independently associated with the 1-year cardiac event rate (HR: 2.15, 95% CI: 1.42-3.26, P < 0.001). Acute HF patients covered by public assistance received the same quality of medical care, including invasive therapy. As a result, no health disparities were found in terms of the in-hospital mortality and 90-day cardiac event rate, unlike overseas surveys. Nevertheless, HF patients with public assistance had a higher risk for the long-term prognosis than those with other insurance. Comprehensive HF management is required post-discharge., (© 2021. This is a U.S. government work and not under copyright protection in the U.S.; foreign copyright protection may apply.)

To prevent early death, management of coagulopathy is important in patients with untreated acute promyelocytic leukemia (APL). This study aimed to clarify factors associated with in-hospital death in patients with coagulopathy during induction therapy for APL. We retrospectively identified patients with newly diagnosed APL who received induction therapy including all-trans retinoic acid (ATRA) and developed coagulopathy, using a nationwide inpatient database in Japan. Of 1115 eligible patients, 175 (15%) died at a median of 13 days (interquartile range, 7-30) after admission. In the multivariable analysis, compared with younger patients (aged < 40 years), the occurrence of in-hospital death was significantly more common among older patients (aged ≥ 40 and < 60 years: odds ratio = 2.58 [95% confidence interval: 1.29-5.19]; aged ≥ 60 and < 80 years: 7.66 [3.89-15.10]; aged ≥ 80 years: 16.83 [7.41-38.21]). Delayed initiation of ATRA and no conventional chemotherapy were significantly associated with in-hospital death (1.79 [1.16-2.76] and 2.40 [1.47-3.92], respectively). A total of 699 patients (63%) received anticoagulant therapies, but none of these was significantly associated with lower mortality. Although the present study was constrained by a lack of laboratory findings because of database limitations, the results showed that untreated patients with APL, especially the elderly, had a poor prognosis. Immediate administration of ATRA may reduce in-hospital mortality., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

We investigated the proliferative effect of a Acanthopanax senticosus extract (ASE) on human CD49f(+)/CD29(+) keratinocytes and isolated phloridzin from A. senticosus as an active compound. In addition, the possible mechanisms of action were examined. We found that the ASE and phloridzin-promoted proliferation of CD49f(+)/CD29(+) cells using MTT and Click-iT™ EdU flow cytometry assays. In addition, phosphorylation of the p44/42 MAPK (ERK), mTOR, p70 S6 kinase (p70S6K), S6 ribosomal protein (S6RP), eukaryotic initiation factor 4B (eIF4B), and eIF4E was stepwise induced in CD49f(+)/CD29(+) cells. Furthermore, the ASE and phloridzin significantly induced the production of vascular endothelial growth factor and interleukin-6 in CD49f(+)/CD29(+) cells. Similarly, ASE and phloridzin-induced phosphorylation of the mTOR/p70S6K/S6RP/eIF4B/eIF4E pathway was blocked in response to pretreatment with PD98059, a specific ERK inhibitor. Taken together, these results indicate that ASE and phloridzin-induced proliferation of CD49f(+)/CD29(+) cells under serum-free conditions was mediated by the ERK-dependent mTOR pathway.

The neuronal responsiveness to three-dimensional (3D) motion in cat posteromedial lateral suprasylvian (PMLS) cortex was studied using a computer-controlled, stereoscopic 3D graphic display capable of reproducing the major visual cues for natural 3D motion, including motion disparity, size, texture, and shading changes. The animals were anesthetized with nitrous oxide supplemented with alphaxalone, and paralysis prevented eye movement. Systematic investigation of neuronal responsiveness to 3D motions in 26 different directions revealed that more than half of the PMLS cells were selectively responsive to approaching (AP cells, 112 of 271) or recessive motion (RC cells, 64 of 271). The remaining cells were selectively responsive to frontoparallel motion (FP cells, 49 of 271) or nonselectively responsive to motion in multiple directions (NS cells, 46 of 271). The dependency on these visual cues was investigated as a reduction in the response amplitude or the response selectivity for the removal of a single cue from the motion stimuli containing the full visual cues. The AP and RC cells showed a strong dependency on the motion disparity cue, moderate dependency on the size cue, and weak dependency on the texture and shading cues. The FP cells showed no dependency on those visual cues. The cue dependency analysis indicated the existence of nonlinear interactions between those visual cues. Comparison of the responses to a combination of the motion disparity and size cues with the summed responses to each of the individual cues revealed that the responses to the combined cues are roughly predicted as a linear sum between the preferred responses. This comparison also showed nonlinear summation between the nonpreferred responses, i.e., responses to the combined cues were smaller than the summed responses. A similar quasilinear summation of the preferred responses between the two eyes and a nonlinear summation of the nonpreferred responses were found in the AP and RC cells for the motion disparity stimulus. All of these observations indicate that quasilinear and nonlinear interactions of the responses to various stimulus elements underlie the 3D motion responsiveness of the PMLS cells.

The telomerase activity and length of telomeres of peripheral blood mononuclear cells obtained from 124 healthy individuals aged 4-95 years was measured. Telomerase activity level was semiquantitatively assessed by a fluorescent-telomeric repeat amplification protocol (fluorescent-TRAP) using an internal telomerase assay standard, fluorescent primers and an automated laser fluorescent DNA sequencer. Telomeric length, measured by assay of terminal restriction fragments (TRFs), was determined in HinfI-digested DNA by Southern blot analysis using a (TTAGGG)4 probe. TRF length was determined in 80 individuals and age-related progressive reduction of size was observed. TRF length in peripheral blood mononuclear cells obtained from normal individuals (aged 4-39 years) decreased by approximately 84 bp per year, while in individuals aged > or = 40 years it decreased by 41 bp per year. In contrast, telomerase activity showed an apparent biphasic pattern with aging. Individuals aged 4-39 years showed a progressive decrease in telomerase activity, whereas 65% of those aged > or = 40 years showed relatively stable but very low telomerase activity, and the remaining individuals aged > or = 40 years had no detectable telomerase activity. These data obtained from normal individuals might in the future be of value to help risk stratify and manage the care of patients with leukemia.

Acyclic retinoid (all-trans-3, 7, 11, 15-tetramethyl-2, 4, 6, 10, 14-hexadecapentaenoic acid) binds cellular retinoic acid-binding protein with an affinity similar to that of all-trans retinoic acid and induces differentiation of human hepatoma cell lines and a human acute myelogenous leukemia cell line (HL-60). We investigated the in vitro efficacy of acyclic retinoid to induce the differentiation of acute promyelocytic leukemia (APL) cells using primary cultured cells obtained from 11 APL patients. Five days' incubation with acyclic retinoid effected a dose-dependent induction of differentiation. Cells from eight patients showed maximum differentiation at 10(-6) M acyclic retinoid. Cells from one patient required 10(-5) M for maximum differentiation, while those from two patients exhibited moderate differentiation at 10(-5) M. Five days' incubation with acyclic retinoid (10(-7) approximately 10(-5) M) did not affect the viability or number of cells from any patient except one, whose cells showed a slight decrease in viability at 10(-5) M. Thus, we conclude that acyclic retinoid induced the differentiation of primary cultured APL cells at concentrations of 10(-6) approximately 10(-5) M, a range at which it is not toxic.

The cell surface phenotype of immunoregulatory lymphocytes in bone marrow (BM) and peripheral blood (PB) in myelodysplastic syndrome (MDS), a stem cell disorder, was analyzed. Mononuclear cells from 25 patients with refractory anemia (RA) and nine with RA with an excess of blasts (RAEB) were characterized by two-color flow cytometry using various monoclonal antibodies. No significant change of CD3+, CD4+, and CD8+ cells in PB, but a decrease of the percent of positive cells for CD8++ among the total lymphocyte (%CD8++) was noticed in RA patients. On the other hand, in BM of RA patients, a decrease in the number of CD4+ cells, but not CD8++ cells, was noted. In RAEB patients, the absolute numbers of CD3+, CD4+, CD8+, and CD8++ cells in BM were decreased; however, the ratio of these lymphocytes was not changed. No change was observed among the CD4+ subsets in PB of RA or RAEB patients. In BM, a decrease in percentage of CD4+CD45RA+ (%CD4+CD45RA+; naive cell) and increases in CD4+CD45RO+ (%CD4+CD45RO+; memory cell) and CD4+CD29+ (%CD4+CD29+; helper/inducer) among CD4+ cells were found in both RA and RAEB patients. Analysis of the CD8++ subset showed an increased number of CD8++CD11a+ cells (activated CTL) in both BM and PB of RA patients, but not of RAEB patients. Furthermore, increments in CD56+ and CD16+ cells among CD3- cells (natural killer; NK cells) were seen in RA patients but not in RAEB patients. It remains unclear whether lymphocytes in MDS patients were involved in the abnormal (MDS) clones, but our results regarding the increments of CD8++CD11a+ and NK cells in RA patients suggest that the mechanism of immune surveillance against the abnormal MDS clones was activated in these RA patients, but not in RAEB patients. Further investigation is required to clarify the functions of these immunoregulatory lymphocytes in MDS patients.

Responsiveness to slits and pattern stimuli was quantified in a total of 68 cells sampled in the posterior extreme of the lateral suprasylvian (PS) cortex as response indices. The cells were studied in relationship to their locations in several subareas of the PS cortex, including areas 19 (n = 15) and 21a (n = 32) and the posteromedial lateral suprasylvian cortex (PMLS; n = 21). These subareas were identified based on retrograde labelling from area 17 and also supplemented with photic responsiveness. This analysis revealed that each cortical area contains cells expressing different combinations of stimulus features. Area 19 contained two major groups of cells: (1) those with strong end-stop selectivity combined with moderate orientation or direction selectivity, and (2) those with weak end-stop selectivity combined with strong orientation selectivity. The groups of cells with strong or moderate orientation selectivity showed a strong preference for stripe over visual noise patterns and relatively large modulatory responses to motion of individual stripes. The PMLS contained one major group of cells with strong end-stop and direction selectivities and with poor orientation selectivity. They also showed stronger preference for visual noise than cells in the other cortical areas and rather weak modulatory responses. Area 21a contained only one group of cells with strong orientation selectivity and length summation property rather than end-stop selectivity, and they also lacked direction selectivity. These cells exhibited a strong preference for stripe patterns and moderate or weak modulatory responses. Altogether, these findings indicate that each cortical area is specialized in expressing different stimulus features. The two groups of cells in area 19 may encode the position and motion of discontinuous visual elements such as corners and line ends and continuous elements such as lines and edges. PMLS cells may encode the motion of single elements or associated motion of multiple discontinuous elements such as textures and backgrounds. Area 21a cells may specifically encode the orientation of long, continuous elements such as lines and edges. In support of this view, two types of statistical analyses demonstrated that the combinations of the response properties expressed in individual PS cells are highly correlated with their locations in cortical areas and that the anatomical locations of individual PS cells are reliably predicted from the sets of response indices expressed in these cells.

Between 1965 and 1991, 241 cases of sporotrichosis have been seen in the Department of Dermatology at Chiba University Hospital. Children under the age of 12 and patients older than 40 years had a higher rate of infection. Most affected were the upper extremities, followed by lesions of the face. One hundred twenty-four patients (51.5%) were farmers. The decrease in the number of patients observed since 1983 is attributed mainly to a drop in the percentage of the local population involved in agriculture. There was no correlation between the number of infections and the amount of precipitation, as had been suggested earlier. The patients were treated with potassium iodide and in some cases with additional thermotherapy.

Superoxide anion (O2-) production and expression of cytochrome b 558 by neutrophils were determined in 20 patients with myelodysplastic syndrome (MDS). The reduction of O2- production was noted in eight of the 20 patients and an increase was noted in four patients when neutrophils were stimulated by n-formyl-methionyl-leucyl-phenylalanine (FMLP), while a low level of O2- production was found in 11 and an increase in six MDS patients when they were stimulated by phorbol myristate acetate (PMA). Among them, seven patients showed a decrease and four an increase in O2- production on stimulation with either FMLP or PMA. Expression of cytochrome b 558 was found to be at low levels in patients who had neutrophils showing decreased O2- production when stimulated with FMLP, indicating that decreased expression of cytochrome b 558 might contribute to the impairment of O2- production in some MDS patients. In this study, no significant differences in O2- production were noted among subtypes of MDS; however, the patients who had received prednisolone showed lower levels of O2- production than those who had not received prednisolone. Patients manifesting episodes of infection had reduced levels of O2- production compared with those without infection. Furthermore, the fact that one patient who exhibited a marked reduction in neutrophil counts together with reduced O2- production died of fatal infection, suggests that the determination of O2- production, in combination with hematological features, may be of some help in predicting severe infection.

Retinotopy and binocular responsiveness were studied extracellularly in a total of 278, 61, 110 and 275 cells sampled in areas 17, 18, 19 and Clare-Bishop (CB) of Siamese cats. The misalignment of the visual axes of the two eyes was determined by the pupil reflex method in the behaving animal. The recording sessions were conducted under N2O anesthesia, supplemented with continuous infusion of short-lasting anesthetics (Saffan, Glaxo) and muscle relaxants (Gallamine triethiodide) using two types of visual stimulators presenting two-dimensional (2D) motion stimuli and the visual cues for three-dimensional (3D) motion. All of the nine Siamese cats demonstrated Boston type retinotopic abnormalities in all of cortical areas 17-19 and CB. Very few binocular cells were present in areas 17-19 and the posterior (A1-P2) CB but they were numerous in most of CB (A9-4). A significant fraction (36/78) of binocular cells in the major CB of the Siamese cats demonstrated similar response selectivity to that reported in normal CB cortex for stimulation with the 3D motion cues under both null disparity and strabismic conditions (binocular receptive fields for two eyes were optically superposed or separated by the strabismic angles estimated in the individual animals). These findings indicate that the binocular signals converging to the CB cells through different pathways (signals coming from the contralateral eye via the ipsilateral hemisphere including the interlaminar nucleus and areas 17-19, and commissural signals from the ipsilateral eye via the contralateral areas 17-19 and CB) were integrated to yield useful information for the recognition of 3D motion, and that the major CB is an actual site of binocular integration at least in Siamese cats, rather than being merely a reflection of the information processing before the CB cortex.

A total of 783 cells were studied extracellularly in anterior (A10-13), posterior (A4-8), and intermediate regions (A8.1-9.9) of Clare-Bishop (CB) cortex of the cat, which were defined according to the anteroposterior coordinate of the stereotaxic axis and probably corresponded to the antero- (AMLS), postero-medial lateral suprasylvian cortex (PMLS), and the border region between the two subareas, respectively. The study was conducted under N2O anesthesia supplemented with continuous infusion of short-lasting anesthetics (Saffan, Glaxo or Etomidate, Janssen), using three types of visual stimulators presenting two- (2D) and three-dimensional (3D) motion stimuli, and visual cues contained in the 3D motion. Neuronal responsiveness was essentially similar between the anterior and posterior CB subdivisions. Both areas contained 1) AP, 2) RC and 3) FP cells, selectively responsive to approaching, recessive and fronto-parallel motion, and 4) NS and 5) U cells, nonselectively responsive and unresponsive to any of these motions. However, a quantitative difference was found: 1) In the posterior CB the FP cell population was the largest, and the frequency reduced in the order of AP, NS, RC and U cells, while the largest population in the anterior CB consisted of the AP and U cells, and the frequency reduced in the order of FP, RC and NS cells. 2) 3D (AP and RC) cells in the posterior CB responded preferentially to approaching motion at a distal range, while those in the anterior CB preferred motion at a proximal range. 3) The 3D cells in the posterior CB were more sensitive to the motion cue and demonstrated lower thresholds for the size cue than the anterior CB cells. 4) The anterior CB cells generally demonstrated high-pass velocity tuning (cut-off around 10 degrees/s) for monoclonal 2D stimulation, while the posterior CB cells demonstrated a broad band-pass tuning (4-120 degrees/s). These findings suggest functional differentiation in neuronal representation of 3D motion signals between the two subdivisions of CB cortex.

Extracellular and intracellular recordings were made from single cells in the pontine nuclei (PN) of the cat. PN cells were identified by antidromic invasion from the cerebellum by stimulating either the brachium pontis (BP) or the white matter near the cerebellar nuclei. The cerebrally-induced impulses excited PN cells postsynaptically with a monosynaptic latency. Both fast and slow conducting cortical fibres contributed to the corticopontine excitation, so that the latency varied over a wide range. Measurements of the latencies for antidromic and corticopontine excitation and of the distances between stimulated sites permitted the calcuation of conduction velocities of PN cell axons and of their cortical input fibres. PN cells with fast conducting axons received convergence from both fast and slow cortical fibres, whereas PN cells with slow axons were innervated only by slow cortical fibres. The majority of PN cells were also excited by stimulating the medullary pyramid through collaterals of the pyramidal tract. Evidence of abundant pyramidal collaterals was provided by the collision technique. The functional role of the PN is discussed in connection with the cerebro-cerebellar loop circuits.

As congenital malformations may be caused by perturbations of glycolytic flux on early embryogenesis [16], effects of hypoglycaemia were investigated by using rat embryo organ culture. Nine and one-half day old rat embryos were grown in vitro for 48 h (day 9 1/2 to 11 1/2) in the presence of hypoglycaemic serum for different hours during the culture period. Hypoglycaemic serum was obtained from rats given insulin intraperitoneally. On exposure to hypoglycaemic serum during the first 24 h of culture (day 9 1/2 to 10 1/2), embryos showed marked growth retardation and had increased frequencies of neural lesions (42.7% versus 0%, p less than 0.01), in contrast to hypoglycaemic exposure during the second 24 h of culture (day 10 1/2 to 11 1/2), where only minor growth retardation and low frequencies of neural lesions (2.4% versus 0%, NS) were seen. Even exposure to hypoglycaemic serum for a relatively short period (8 h) during the first 24 h of culture resulted in neural lesions at the frequency of 9.3-13.3%. The embryos exposed to hypoglycaemia demonstrated decreased glucose uptake and lactic acid formation, indicating decreased energy production via glycolysis that constitutes the principal energy pathway at this stage of embryonic development. These results suggest that hypoglycaemia during critical periods of embryogenesis has adverse effects on the development of the embryo and these effects might be mediated through metabolic interruption of embryogenesis.

1. Intracellular potentials of pontine nuclei (PN) cells were recorded in cats anesthetized with pentobarbitone sodium. 2. Stimulation of the cerebellar nuclear regions or the brachium pontis induced an antidromic action potential composed of IS-SD spikes, after-depolarization and after-hyperpolarization. 3. Cerebellar stimulation produced EPSPs only in a few PN cells. 4. Activation of the corticopontine or pyramidal tract produced in all PN cells an EPSP built up from the unitary components with variable amplitudes and time courses. Paired or repetitive activation revealed a property of the frequency potentiation of the EPSP. 5. Unitary EPSPs also occurred spontaneously. A great majority of these spontaneous EPSPs were cerebral in origin, and had amplitudes and time courses comparable with those evoked by stimulation of the corticopontine or pyramidal tract. 6. The half-width versus time of peak relationship of these unitary EPSPs suggested a dendritic location of the synapses with variable distances from the soma. It is assumed that large, proximal synapses serve for efficient relay of signals while small, distal synapses for their integration.