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Masaki Sakurai

Publications and source records attributed to Masaki Sakurai.

9 recordsLinked to original sources

Synapse elimination in the corticospinal projection during the early postnatal period.

In corticospinal synapses reconstructed in vitro by slice co-culture, we previously showed that the synapses were distributed across the gray matter at 6-7 days in vitro (DIV). Thereafter, they began to be eliminated from the ventral side, and dorsal-dominant distribution was nearly complete at 11-12 DIV. The synapse elimination is associated with retraction of the corticospinal (CS) terminals. We studied whether this specific type of synapse elimination is a physiological phenomenon rather than in vitro artifact. The rat corticospinal tract was stimulated at the medullary pyramid, and field potentials were recorded at the cervical cord along an 200-microm interval lattice on the axial plane. Clearly defined negative field potential were identified as field excitatory postsynaptic potentials (fEPSPs) generated by corticospinal synapses. They were recorded from the entire spinal gray matter at postnatal day 7 (P7). These negative fEPSPs reversed to positive in the most ventrolateral part at P8. Reversal extended to the more mediodorsal area at P10, indicative of progressive synapse elimination in the ventrolateral area. To verify that regression of the axons in vivo paralleled the changes in spatial distribution of fEPSPs as observed in vitro, corticospinal axons were anterogradely labeled. Redistribution of the labeled terminals closely paralleled the fEPSP distribution, being present in the ventrolateral spinal cord at P7, decreased at P8, further deceased at P10, but unchanged at P11. Furthermore, double immunostaining for labeled terminals and synaptophysin observed under a confocal microscope suggests that corticospinal fibers at P7 possess presynaptic structures in the ventrolateral area as well as the dorsomedial area. These findings suggest that corticospinal synapses are widely formed in the spinal gray matter at P7, are rapidly eliminated from the ventrolateral side from P8 to P10, a time-course very similar to that observed in vitro, and are associated with axonal regression.

6-Cyano-7-nitroquinoxaline-2,3-dione↗

Characterization of the VP1 loop mutations widespread among JC polyomavirus isolates associated with progressive multifocal leukoencephalopathy.

Recently, we found that JC polyomavirus (JCPyV) associated with progressive multifocal leukoencephalopathy (PML) frequently undergoes amino acid substitutions (designated VP1 loop mutations) in the outer loops of the major capsid protein, VP1. To further characterize the mutations, we analyzed the VP1 region of the JCPyV genome in brain-tissue or cerebrospinal fluid samples from 20 PML patients. VP1 loop mutations occurred far more frequently than silent mutations. Polymorphic residues were essentially restricted to three positions (55, 60, and 66) within the BC loop, one (123) within the DE loop, and three (265, 267, and 269) within the HI loop. The mutations at most polymorphic residues showed a trend toward a change to specific amino acids. Finally, we presented evidence that the VP1 loop mutations were associated with the progression of PML. These findings should form the basis for elucidating the biological significance of the VP1 loop mutations.

Autopsy↗

Regionally specific distribution of corticospinal synapses because of activity-dependent synapse elimination in vitro.

We have shown previously that the corticospinal tract (CST) with functional connections can be reconstructed in vitro in slice cocultures. Using that system, we stimulated the deep cortical layer and recorded field EPSPs (fEPSPs) along a 100 microm-interval lattice in the spinal gray matter. The specific, spatial synapse distribution on the dorsal side at 14 d in vitro (DIV) basically corresponded to the in vivo area in which CST axons terminate. Anterograde labeling of corticospinal axons with biocytin showed a similar terminal distribution on that side. In vitro development of synapse spatial distribution was investigated. fEPSPs were recorded all across the gray matter at 7 DIV, but amplitudes began to decrease on the ventral side at 9 DIV, dorsal-dominant distribution being nearly complete at 14 DIV. Anterograde labeling showed that the decrease in fEPSP amplitudes was associated with a decrease in the number of axon terminals on the ventral area. Decreases in the synaptic responses and terminals were blocked by applications of D-2-amino-5-phosphonovaleric acid and tetrodotoxin, whereas 6-cyano-7-nitroquinoxaline-2,3-dione had a partial effect. These findings suggest that this regressive event, which occurs during development, is activity and NMDA dependent. Retrograde labeling with two colors of beads and an electrophysiological study that investigated the axon reflex showed that at 7 DIV most corticospinal neurons project to both the ventral and dorsal spinal cord, indicating that synapse decrease on the ventral side is attributable primarily to axon branch elimination rather than to death of cortical cells that send axons solely to that side.

Animals↗

[Licorice of 'shakuyaku kanzou tou' induced pseudoaldosteronism].

We report a case of pseudoaldosteronism induced by licorice in a kampo medication 'Shakuyaku Kanzou Tou' that was diagnosed after relief of urinary retention due to benign prostatic hypertrophy (BPH). A-71-year-old man was admitted to our hospital due to urinary retention. At admission, he had hypertension and leg edema, but serum potassium was in the normal range. One day after admission, hypokalemia was recognized. He was taking "Shakuyaku Kanzou Tou", a Chinese medicine that contains glycyrrhizin. So we suspected pseudoaldosteronism and had him stop taking it. Computed tomography did not reveal any adrenal tumor. Plasma rennin activity and aldosterone level were suppressed. Gradually, hypertension and leg edema improved and serum potassium became within the normal range. We diagnosed the case as pseudoaldosteronism induced by licorice of 'Shakuyaku Kanzou Tou'. Since we suspected BPH to be the cause of urinary retention, we performed transurethral resection of prostate. After surgery, he was able to void smoothly.

Aged↗

[Case of presacral dermoid cyst].

A case report of a presacral dermoid cyst in an adult. A 39-year-old man visited our hospital because of lower abdominal pain. A soft mass was palpable on the right side wall of rectum. Computed tomographic (CT) scan, transrectal ultrasonography and MR imaging showed presacral cystic tumor with a diameter of 10 cm. The tumor was resected by using a sacral approach. It contained muddy substance and hairs. Histopathological examination showed that the tumor wall was made of stratified squamous epithelium with skin appendage. Hence, it was diagnosed as a dermoid cyst. After operation, wound infection and dehiscence occurred, but it healed after conservative treatment. Complete excision of developmental cysts is advised because of possibility of malignancy and infection.

Abdominal Neoplasms↗

[Two cases of prostate cancer associated with acute myeloid leukemia presenting as thrombocytopenia during endocrine therapy].

Prostate is one of the most common sites of multiple primary cancer (MPC). We herein present two cases of prostate cancer associated with acute myeloid leukemia (AML) presenting as thrombocytopenia during endocrine therapy. After a diagnosis of prostate cancer (stage D2) was made, our patients received endocrine treatment with fosfestrol followed by a luteinizing hormone-releasing hormone (LH-RH) analogue and bicaltamide. Thrombocytopenia appeared 8 months and 10 months after the initiation of endocrine therapy, respectively. Because suspensions of bicaltamide resulted in further deterioration of thrombocytopenia, bone marrow aspirations were done with hematological examination revealing features of the M2 subtype of AML. Review of MPC with prostate cancer in the literature suggested that the combination of prostate cancer and AML was rare.

Adenocarcinoma↗