Flunarizine induces a transient loss of tyrosine hydroxylase immunoreactivity in nigrostriatal neurons

Neurotoxic effects of flunarizine (Fz), a selective calcium channel blocker, on the nigrostriatal dopamine system was investigated. Systemic injections of Fz to mice resulted in a transient loss of tyrosine hydroxylase (TH) immunoreactive nigrostriatal neurons without cell loss. TH immunoreactivity in these neurons was greatly reduced as rapidly as one day after drug administration (regardless of dosage used) and thereafter recovered in both dose- and time-dependent manners. Such a novel neurotoxic action of Fz may constitute a morphological substrate for reversible drug-induced parkinsonian signs described in recent clinical case reports.     

Induction of radioresistance to accelerated carbon-ion beams in recipient cells by nitric oxide excreted from irradiated donor cells of human glioblastoma

PURPOSE: To investigate whether nitric oxide excreted from cells irradiated with accelerated carbon-ion beams modulates cellular radiosensitivity against irradiation in human glioblastoma A-172 and T98G cells. MATERIALS AND METHODS: Western-blot analysis of inducible nitric oxide synthase, hsp72 and p53, the concentration assay of nitrite in medium and cell survival assay after irradiation with accelerated carbon-ion beams were performed. RESULTS: The accumulation of inducible nitric oxide synthase was caused by accelerated carbon-ion beam irradiation of T98G cells but not of A-172 cells. The accumulation of hsp72 and p53 was observed in A-172 cells after exposure to the conditioned medium of the T98G cells irradiated with accelerated carbon-ion beams, and the accumulation was abolished by the addition of an inhibitor for inducible nitric oxide synthase to the medium. The radiosensitivity of A-172 cells was reduced in the conditioned medium of the T98G cells irradiated with accelerated carbon-ion beams compared with conventional fresh growth medium, and the reduction of radiosensitivity was abolished by the addition of an inducible nitric oxide synthase inhibitor to the conditioned medium. CONCLUSIONS: Nitric oxide excreted from the irradiated donor cells with accelerated carbon-ion beams could modulate the radiosensitivity of recipient cells. These findings indicate the importance of an intercellular signal transduction pathway initiated by nitric oxide in the cellular response to accelerated heavy ions.     

Usefulness of intraoperative computed tomography in surgery for low-grade gliomas: a comparative study between two series without and with intraoperative computed tomography

We have routinely used an intraoperative CT (i-CT) system in over 800 neurosurgical procedures since 1997. To investigate the utility of i-CT in low-grade glioma (LGG) surgery, we investigated whether i-CT improved the extent of tumor resection and prognosis in 46 patients with histologically confirmed LGG consisting of 27 patients with World Health Organization grade II astrocytoma, 12 with oligodendroglioma, and 7 with oligoastrocytoma. The patients were divided into two groups, 23 who underwent tumor resection without i-CT (non i-CT group) and 23 who underwent surgery using i-CT (i-CT group). We investigated the extent of tumor resection, pre- and postoperative Karnofsky performance status scores, and overall survival in each group. The extent of tumor resection was biopsy 26.1%, partial resection 60.9%, subtotal resection 13.0%, and gross total resection 0% in the non i-CT group, and 4.4%, 21.7%, 34.8%, and 39.1%, respectively, in the i-CT group. The i-CT group showed significantly longer overall survival than the non i-CT group among patients with astrocytoma (p < 0.05) and oligodendroglioma or oligoastrocytoma (p < 0.005). Prolonged survival was related to the extent of resection. There were no significant differences between pre- and postoperative Karnofsky performance status scores between the groups. Surgical resection using i-CT may improve the outcomes of patients with LGG. Additional resection or emergency treatment can be quickly performed as the surgical results are confirmed intraoperatively or immediately after the operation using i-CT.     

The analysis of mitral annular disjunction detected by echocardiography and comparison with previously reported pathological data

Background

Mitral annular disjunction is a structural abnormality of the mitral annulus fibrosus and is pathologically defined by a separation between the atrial wall–mitral valve junction and the left ventricular attachment. Mitral annular disjunction can cause hypermobility of the mitral valve apparatus and is often associated with mitral valve prolapse (MVP). The aim of this study was to investigate the frequency and characteristics of mitral annular disjunction in the patients referred to an echocardiography laboratory and to compare these with previously reported pathological data.

Methods and results

We retrospectively studied 1439 patients (mean age 65 ± 17 years, 58% male) referred to our echocardiography laboratory from 6 January 2014 to 31 March 2014. The echocardiographic parameters were compared between the patients with and without mitral annular disjunction. There were 125 cases (8.7%) with mitral annular disjunction, of which 15 (12%) also had MVP. The number of MVP patients in the group with mitral annular disjunction was significantly larger than in the group without mitral annular disjunction (p < 0.0001). The grade of mitral regurgitation was not significantly different between the two groups.

Conclusions

Mitral annular disjunction was detected not only in patients with a myxomatous mitral valve but also in normal cases. The number of MVPs was significantly larger in patients with mitral annular disjunction than patients without mitral annular disjunction. Further investigation is needed to clarify the clinical significance of the mitral annular disjunction detected by routine echocardiography.

     

Acute Lymphoblastic Leukemia with t(1;19)(q23;p13)/TCF3-PBX1 Fusion in an Adult Male with Down Syndrome

No abstract available.     

Localization and function of the accessory protein Mfa3 in Porphyromonas gingivalis Mfa1 fimbriae

The fimbriae of Porphyromonas gingivalis, the causative agent of periodontitis, have been implicated in various aspects of pathogenicity, such as colonization, adhesion and aggregation. Porphyromonas gingivalis ATCC 33277 has two adhesins comprised of the FimA and Mfa1 fimbriae. We characterized the PGN0289 (Mfa3) protein, which is one of the three accessory proteins of Mfa1 fimbriae in P. gingivalis. The Mfa3 protein was present in two different sizes, 40 and 43 kDa, in the cell. The 43‐kDa and 40‐kDa Mfa3 were detected largely in the inner membrane and the outer membrane, respectively. Purified Mfa1 fimbriae contained the 40‐kDa Mfa3 alone. Furthermore, the 40‐kDa Mfa3 started with the Ala⁴⁴ residue of the deduced amino acid sequence, indicating that the N‐terminal region of the nascent protein expressed from the mfa3 gene is processed in the transport step from the inner membrane into fimbriae. Immuno‐electron microscopy revealed that Mfa3 localized at the tip of the fimbrial shaft. Interestingly, deletion of the mfa3 gene resulted in the absence of other accessory proteins, PGN0290 and PGN0291, in the purified Mfa1 fimbriae, suggesting that Mfa3 is required for integration of PGN0290 and PGN0291 into fimbriae. A double mutant of mfa3 and fimA genes (phenotype Mfa1 plus, FimA minus) showed increased auto‐aggregation and biofilm formation similar to a double mutant of mfa1 and fimA genes (phenotype Mfa1^–, FimA^–). These findings suggest that the tip protein Mfa3 of the Mfa1 fimbriae may function in the integration of accessory proteins and in the colonization of P. gingivalis.     

Cholinergic and noncholinergic tegmental pedunculopontine projection neurons in rats revealed by intracellular labeling

Morphological features of rat pedunculopontine projection neurons were investigated in in vitro preparation by using intracellular labeling with biocytin combined with choline acetyltransferase (ChAT) immunohistochemistry. These neurons were classified into two types (Type I and II), based on their electrical membrane properties: Type I had low-threshold Ca²⁺ spikes, and Type II had A-current. All Type I neurons (n = 17) were ChAT immunonegative (ChAT⁻). Type II neurons were either ChAT immunopositive (ChAT⁺; n = 49) or ChAT⁻ (n = 20). In terms of topography in the tegmental pedunculopontine nucleus (PPN), Type I neurons were dispersed throughout the extent of the nucleus, whereas Type II neurons tended to be located more in the rostral and middle sections. Both Type I and II neurons consisted of small (long axis <20 μm), medium (20–35 μm), and large (>35 μm) cells. The small cells were round or oval; medium cells were round, triangular, or fusiform; and the large cells were primarily fusiform in shape. In terms of the soma size, there was a difference in Type I (15–38 μm) and Type II (11–50 μm) neurons, but no significant difference was found between Type II ChAT⁻ and ChAT⁻ cells. Both types of neurons had three to six primary dendrites, but the dendritic field was more prominent in Type II neurons. Most of the axons originated from one of the primary dendrites, which gave off axon collaterals, some of which projected out of the nucleus. The intrinsic collaterals were thin and branched party within the dendritic field of the parent cell. The extrinsic collaterals were thicker and could be grouped into three categories: 1) collaterals arborizing in the substantia nigra; 2) collaterals ascending mainly toward the thalamus, pretectal, and tectal area; and 3) collaterals descending toward the mesencephalic and/or pontine reticular formation. It was noted that the collaterals of both ChAT⁺ and ChAT⁻ neurons were traced into the substantia nigra. There was no significant difference in antidromic latencies between Type I (m = 1.47 msec) and Type II (m = 1.36 msec) neurons following electrical stimulation of the substantia nigra. © 1996 Wiley-Liss, Inc.