Cytoprotective Effects of Mesenchymal Stem Cells During Liver Transplantation from Donors After Cardiac Death in Rats.

BACKGROUND: Liver transplantation from donors after cardiac death (DCD) might increase the pool of available organs. Recently, some investigators reported the potential use of mesenchymal stem cells (MSCs) to improve the outcome of liver transplantation from DCD. The aim of this study was to evaluate the cytoprotective effects and safety of MSC transplantation on liver grafts from DCD. METHODS: Rats were divided into 4 groups (n = 5) as follows: 1. the heart-beating group, in which liver grafts were retrieved from heart-beating donors; 2. the DCD group, in which liver grafts were retrieved from DCD that had experienced apnea-induced agonal conditions; 3. the MSC-1 group, and 4. the MSC-2 group, in which liver grafts were retrieved as with the DCD group, but were infused MSCs (2.0 × 105 or 1.0 × 106, respectively). The retrieved livers were perfused with oxygenated Krebs-Henseleit bicarbonate buffer (37°C) through the portal vein for 2 hours after 6 hours of cold preservation. Perfusate, bile, and liver tissues were then investigated. RESULTS: Bile production in the MSC-2 group was significantly improved compared with that in the DCD group. Based on histologic findings, narrowing of the sinusoidal space in the both MSC groups was improved compared with that in the DCD group. CONCLUSIONS: MSCs could protect the function of liver grafts from warm ischemia-reperfusion injury and improve the viability of DCD liver grafts. In addition, we found that the infusion of 1.0 × 106 MSCs does not obstruct the hepatic sinusoids of grafts from DCD.

Incidental acute infarcts identified on diffusion-weighted images: a university hospital-based study.

BACKGROUND AND PURPOSE: Pathogenesis of leukoaraiosis is incompletely understood and accumulation of small infarctions may be one of the possible sources of such white matter lesions. Thus, the purpose of this study was to identify the rate of incident infarction as depicted on diffusion-weighted images (DWIs) obtained from a general patient population. MATERIALS AND METHODS: During the 4-year study period, a total of 60 patients (36 men and 24 women) had an incidental DWI-defined infarction without overt clinical symptoms suggestive of a stroke or a transient ischemic attack. All of the MR images were obtained by using a similar protocol on 2 identical 1.5T whole-body scanners. The patient's vascular risk factors, as well as the presence of white matter lesions (WMLs) on MR imaging and atheromatous changes on MR angiography, were assessed retrospectively. The incidental DWI-defined infarcts were also characterized in terms of their lateralization, lobe, and specific location. RESULTS: A total of 16,206 consecutive brain MR images were done during the study period; the overall incidence of incidental infarcts was 0.37%. Most of these patients with an incidental infarct had vascular risk factors and WMLs on MR images. Most of these patients (80%) had a single lesion on DWI. A total of 88 lesions were identified; most were located in the white matter of the supratentorial brain, primarily in the frontoparietal lobes. There were also lesions involving the brain stem (n = 2). The lesions involving cerebrum were more commonly located in the right side (right to left = 52:34). CONCLUSION: Small, DWI-defined acute brain infarctions can be found incidentally in an asymptomatic population; this finding may account, at least in part, for the pathogenesis of WMLs identified on MR imaging.

Multitensor tractography enables better depiction of motor pathways: initial clinical experience using diffusion-weighted MR imaging with standard b-value.

BACKGROUND AND PURPOSE: The purpose of this work was to test the feasibility of using high angular resolution diffusion imaging (HARDI)-based multitensor tractography to depict motor pathways in patients with brain tumors. MATERIALS AND METHODS: Ten patients (6 males and 4 females) with a mean age of 52 years (range, 9-77 years) were scanned using a 1.5T clinical MR unit. Single-shot echo-planar imaging was used for diffusion-weighted imaging (repetition time, 6000 ms; excitation time, 88 ms) with a diffusion-sensitizing gradient in 32 orientations and a b-value of 1000 s/mm(2). Data postprocessing was performed using both the conventional single- and multitensor methods. The depiction rate of the 5 major components of the motor pathways, that is, the lower extremity, trunk, hand, face, and tongue, was assessed. RESULTS: Motor fibers on both lesional and contralesional sides were successfully depicted by both the single-tensor and multitensor techniques. However, with the single-tensor model, the depiction of motor pathways was typically limited to the fibers of trunk areas. With the multitensor technique, at least 4 of 5 major fiber bundles arising from the primary motor cortex could be identified. CONCLUSION: HARDI-based multitensor tractography using a standard b-value (1000 s/mm(2)) can depict the fiber tracts from the face and tongue regions of the primary motor cortex.

A case of diastematomyelia associated with myeloschisis in a hemicord.

We report a case of myeloschisis on the right hemicord in a patient with diastematomyelia. The patient was a female neonate with myeloschisis visible at birth in the upper lumbar region. Radiological examination, including three-dimensional CT and MRI, clearly revealed a bony septum as well as the myeloschisis on the right hemicord, which enabled us to make a precise preoperative diagnosis of this complex anomaly. Closure of the myeloschisis and removal of the septum were successfully accomplished in one stage to prevent subsequent infection and neurological deterioration. The presence of combined diastematomyelia and myeloschisis is consistent with the hypothesis of an ontogenic basis of development and emphasizes the importance of early imaging for diagnosis in this complex anomaly.

[Relationship of postoperative residual air and recurrence in chronic subdural hematoma].

The possibility exists that residual air after surgery is one cause of recurrence of chronic subdural hematoma. We have devised a new simple method which decreases postoperative residual air, using external drainage and an endoscope. First, we make endoscopic observations of the inner aspect of the hematoma cavity. Then, we insert external drainage apparatus into the most frontal area of the hematoma cavity, we regard this location as the most appropriate place to ensure most effective drainage. The present study included 37 chronic subdural hematomas in 32 patients who had been treated between January and December, 1999. Their ages ranged from 48 to 86 years old, with an average of 72 years. Insertion of external drainage in the most frontal area of the hematoma cavity was successfully achieved in 27 (73%, Group I) out of 37 cases and resulted in no recurrence. In the remaining 10 hematomas (27%, Group II), external drainage was not able to be inserted in the most frontal area, and four hematomas (40%) had recurrence (p < 0.01 vs Group I). Insertion in the most frontal area of the hematoma cavity decreases residual air after surgery, and may be effective for the prevention of recurrence of chronic subdural hematoma.

Assembly of the 26S proteasome is regulated by phosphorylation of the p45/Rpt6 ATPase subunit.

We investigated whether the assembly/disassembly of the 26S proteasome is regulated by phosphorylation/dephosphorylation. The regulatory complex disassembled from the 26S proteasome was capable of phosphorylating the p45/Sug1/Rpt6 subunit, suggesting that the protein kinase is activated upon dissociation of the 26S proteasome or that the phosphorylation site of p45 becomes susceptible to the protein kinase. In addition, the p45-phosphorylated regulatory complex was found to be incorporated into the 26S proteasome. When the 26S proteasome was treated with alkaline phosphatase, it was dissociated into the 20S proteasome and the regulatory complex. Furthermore, the p45 subunit and the C3/alpha2 subunit were cross-linked with DTBP, whereas these subunits were not cross-linked by dephosphorylating the 26S proteasome. These results indicate that the 26S proteasome is disassembled into the constituent subcomplexes by dephosphorylation and that it is assembled by phosphorylation of p45 by a protein kinase, which is tightly associated with the regulatory complex. It was also revealed that the p45 subunit is directly associated with the 20S proteasome alpha-subunit C3 in a phosphorylation-dependent manner.

Arterial relaxation mediated by endothelium-derived hyperpolarizing factor in hypertension induced by chronic inhibition of nitric oxide synthesis.

The aim of this study was to evaluate arterial relaxation mediated by endothelium-derived hyperpolarizing factor (EDHF) during chronic inhibition of nitric oxide (NO) synthase. We measured the isometric tension of isolated mesenteric arteries of Wistar rats administered Nomega-nitro-L-arginine methyl ester (L-NAME, 100 mg/Kg/day) for 3 weeks. Relaxation to acetylcholine (ACh) was reduced in L-NAME treated rats (maximum relaxation, 52% versus 79% ). After acute superfusion of 1x10(-4) M L-NAME, half the relaxation was inhibited in controls, while the relaxation was not changed in L-NAME treated rats. In contrast, relaxation to nitroprusside was normal in L-NAME treated rats. Superfusion of 1x10(-6) M apamin, which inhibits the effects of EDHF, reduced the relaxation. The relaxation inhibited by apamin was not significantly different between the two groups. These findings suggested that in endothelial cells, the synthesis of EDHF is unchanged during a chronic deficiency of relaxation influence of NO.

Significance of hearing preservation in acoustic neuroma surgery.

In the past 10 years, 43 patients with acoustic neuroma have been operated on by the middle cranial fossa approach. In all cases, meticulous care was taken to preserve the cochlear function regardless of the degree of preoperative hearing disorder. Thirty-nine of 43 patients had various degrees of residual hearing, hearing was preserved in 16 of these (41%). The best result was obtained in patients with a tumor located less than 1 cm from the porus. The hearing preservation rate was 64% (11/17). The patients recovered hearing acuity quite well, especially at low frequencies in 2 cases who had a pure tone hearing level of more than 50 dB and less than 50% of speech discrimination. These 2 cases had a history of sudden deafness that was intractable 5 months preoperatively. Thus it is not correct to set certain criteria for hearing preservation for patients whose preoperative hearing may not be serviceable.

[Superficial siderosis appeared in a case of suprasellar embryonal carcinoma].

A case of superficial siderosis that appeared in a case of suprasellar embryonal carcinoma is reported. A 24-year-old man presented polydipsia and vertigo. MRI revealed a suprasellar tumor. The tumor contained high intense spots on T1-weighted images, suggesting intratumoral hemorrhage. He underwent a surgery, which proved it as embryonal carcinoma pathologically. Cerebrospinal fluid was xanthochromic at surgery, suggesting terminal hemorrhage. After surgery, he received a total dose of 56 Gy of irradiation. Tumor decreased in size and symptoms improved. However, he presented occipital headache 7 months after surgery. MRI showed disseminated tumors in the subarachnoid spaces. He received irradiation for the whole spine and adjuvant chemotherapy. During treatment, MRI demonstrated low signals on the surface of the brain stem, suggesting the superficial siderosis. The lesions spread to the surface of the cerebellum and tentorium cerebelli. Superficial siderosis is characterized by the deposition of hemosiderin in the leptomeninges, cranial nerves and spinal cord. The etiology of the hemosiderin deposition is thought to be chronic or recurrent bleeding into subarachnoid space. Experimentally, similar lesions have been produced in the animals following intrathecal injection of blood or hemolysed red cells. In the literature, MRI demonstrated a rim of marked hypo-intensity on T2-weighted images, consistent with hemosiderin deposits, on the surface of cerebellum and brain stem. Gradient-echo sequences have been more sensitive than T2-weighted images of spin echo sequences. In the present case, the superficial siderosis seems to be due to chronic tumoral hemorrhage. This phenomenon could be related to chemotherapy using CDDP and etoposide.

Development of a huge varix following endovascular embolization for cerebellar arteriovenous malformation. A case report.

We report on the case of a huge varix that developed after the endovascular embolization of a cerebellar arteriovenous malformation (AVM) with a single drainer. A 21-year-old male presented with trigeminal neuralgia which was caused by the dilated drainer of the AVM. A varix was found at the basal vein of Rosenthal 2 months after an initial stage of embolization with polyvinyl alcohol particles; it diminished after the surgical extirpation of the AVM. The varix formation might have been facilitated by the stenosis in the vein of Galen and by the dynamic changes that followed the embolization. This rare complication should be kept in mind when embolization is performed for AVMs with impaired venous outlets.

[Laparoscopic retrieval of a dislocated ventriculoperitoneal shunt catheter: report of three cases and a review of the literature].

Described are 3 cases of a disconnected ventriculoperitoneal shunting system that was successfully retrieved by using a laparoscopic procedure, with a review of the literature. All patients had symptoms of increased intracranial pressure. Roentgenograms showed disconnection of a ventriculoperitoneal shunt catheter at the connecting device and its migration into the peritoneal cavity. A laparoscope was introduced into the peritoneal cavity using the double puncture procedure and the catheter was extracted in less than 15 minutes. The use of a laparoscope enabled exploration of the entire space of the cavity without any large laparotomy incision. Furthermore, the laparoscopic procedure also easily enabled introduction of a replaceable ventriculoperitoneal shunt catheter into the appropriate portion in the cavity and confirmed the CSF flow into the cavity. Because catheters which have migrated into the cavity might cause an acute abdomen, it is important that they should be removed as soon as possible. It should be kept in mind, during the procedures of extracting catheters, that the inner absorptive surface of the peritoneal cavity must be preserved as much as possible. In this regard, laparoscopic retrieval of disconnected shunt catheters is a promising method.

Unilateral acoustic neuroma in childhood.

Three cases of unilateral acoustic neuroma in childhood that are associated with neither neurofibromatosis type 1 nor type 2 were reported. All three cases had a hearing disorder as an initial symptom. Two of them had a large neuroma and had considerable abnormal findings in neurootological examinations, and one case with an intracanalicular tumor showed a unilateral progressive sensorineural hearing loss that had no response to steroid administration. Surgical removal of the tumor was carried out for these cases. Different approaches were used in each case; suboccipital approach, one-stage suboccipital and middle fossa approach, and middle fossa approach. Although the facial nerve functions were fairly well maintained, hearing preservation could not be attained in all. Papers dealing with this tumor were reviewed, and certain characteristics of cases with acoustic neuroma in childhood were discussed.

Increased Ca2+ sensitivity of contractile elements via protein kinase C in alpha-toxin permeabilized SMA from young spontaneously hypertensive rats.

OBJECTIVE: The purpose of the present investigation was to examine the Ca2+ sensitivity of the contractile elements via protein kinase C (PKC) in superior mesenteric artery (SMA) from young (5-6 weeks old) spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats (WKY). METHODS: Staphylococcal aureus alpha-toxin, which produces pores in the plasma membrane too small to allow passage of proteins such as PKC, was used to investigate the signal transduction system in vascular smooth muscle cells. We investigated the Ca2+ sensitivity of the contractile apparatus via PKC in intact and alpha-toxin skinned SMA from young SHR and WKY. RESULTS: In intact SMA, high K+ responses were not different between SHR and WKY. However, phorbol 12,13-dibutyrate (PDBu, a PKC activator) augmented high K(+)-evoked contractions and PKC inhibitors, such as 1-(5-isoquinolinesulfonyl)-2-methylpiperazine (H-7) and calphostin C, suppressed them more in SHR as compared with WKY. In alpha-toxin skinned SMA, the [Ca2+]i-force relationship curve was not significantly different between SHR and WKY. However, PDBu augmented [Ca2+]i-evoked contractions and PKC inhibitors suppressed them more in SHR than in WKY. CONCLUSION: These results suggest that the Ca2+ sensitivity of the contractile elements via PKC is significantly greater in prehypertensive SHR than in age-matched WKY. This abnormality in small muscular arteries may be involved in the pathogenesis of hypertension in SHR.

Preliminary results with technetium-99m MIBI SPECT imaging in patients with brain tumors: correlation with histological and neuroradiological diagnoses and therapeutic response.

SPECT using Tc-99m MIBI was performed in patients with brain tumors in order to determine Tc-99m MIBI uptake in brain tumors and to evaluate the efficacy of MIBI imaging in the assessment of treatment response. A MIBI uptake index was calculated on SPECT imaging. All tumors with a MIBI-index higher than 7.5 were malignant. In the tumors evaluated before and after radiochemotherapy, the MIBI-index immediately following therapy correlated with treatment response 2 months after therapy. Thus, semiquantitative assessment using Tc-99m MIBI SPECT imaging may be useful in the evaluation of treatment response.

Fractional Ca2+ release from the endoplasmic reticulum activates Ca2+ entry in freshly isolated rabbit aortic endothelial cells.

The purpose of the present investigation was to examine the correlation between rates of endoplasmic reticulum (ER) depletion and activation of store operated channels (SOC) in freshly isolated rabbit aortic endothelial cells. We investigated the effects of 10 microM cyclopiazonic acid (CPA), 10 microM ryanodine, and 10 mM caffeine on the rate of Ca2+ depletion from the ER and on Ca2+ and Mn2+ influx using fura-2 fluorescence. We observed that the spontaneous loss of the ACh-sensitive pool is slow. Activation of ryanodine receptors (caffeine, ryanodine) or inhibition of the ER Ca2+ pump (CPA) increased the rate of Ca2+ loss from the ACh-sensitive pool. CPA stimulated Mn2+ influx, while caffeine and ryanodine did not. Our results show non linear correlation between ER depletion and activation of divalent cation entry. In the case of CPA, less than 20% depletion of the ACh sensitive store was required for full activation of SOC, while caffeine and ryanodine deplete over 50% of the ACh sensitive store without activating any influx. These data suggest that only a small compartment of the ER is involved in regulation of Ca2+ entry.

Inhibition of methionine uptake by cis-diamminedichloroplatinum (II) in experimental brain tumors.

cis-diamminedichloroplatinum (II) (CDDP) has been used both alone and in combination with other chemotherapeutics for cancer chemotherapy. Although CDDP acts primarily on DNA, it can also act at the tumor-cell membrane to inhibit methionine transport. The latter mechanism of CDDP is reported to have an important role as a chemical modulator in enhancing chemotherapeutic effects of 5-fluorouracil in tumor cells. We report here the effects of CDDP on methionine uptake in an in vivo brain-tumor model. C6 brain-tumor cells were stereotactically inoculated in the right basal ganglia of 6-week-old male Sprague-Dawley rats. Ten days after the inoculation, autoradiographic images were obtained using (14C-methyl)-L-methionine. The tracer uptake, represented as differential absorption ratio (DAR) and an acid-insoluble fraction (AIF), was measured in both brain tumors and normal brain with or without an intravenous injection of CDDP. The tumor/non-tumor DAR and AIF decreased significantly (P < 0.01, as determined by the Mann-Whitney U-test) after CDDP treatment, whereas the non-tumor DAR and AIF remained almost unchanged. These findings indicate that CDDP inhibits methionine uptake selectively in brain-tumor tissue and may therefore be a potent chemical modulator in the chemotherapy of brain tumors.

Intramedullary spinal cord germinoma: case report and review of the literature.

We discuss the case of a patient with a recurring intramedullary spinal cord germinoma of the lower thoracic spinal cord, which was successfully excised. A primary intramedullary spinal cord germinoma is very rare, and only four other cases have been reported in the literature. All five cases are reviewed regarding the appearance of the germinomas, their neuroradiological features, and their histopathological findings. We also discuss treatment choices for germinomas of the spinal cord.

Blood flow and metabolism of central neurocytoma: a positron emission tomography study.

BACKGROUND: New World Health Organization classifications have categorized central neurocytomas as neuronal tumors. The differential diagnosis between central neurocytomas and other tumors is important for selection of the optimal therapy modality for the management of intraventricular tumors. To characterize the pathophysiology and proliferating activity of central neurocytoma accurately, cerebral blood flow and metabolism in five patients with central neurocytoma were studied using positron emission tomography (PET). METHODS: Tracers used for the present study included C15O2, C15O, 15O2, and 18F-fluorodeoxyglucose (FDG). Regional cerebral blood flow (rCBF), cerebral blood volume (rCBV), oxygen extraction fraction (rOEF), cerebral metabolic rate of oxygen (rCMRO2), and cerebral metabolic rate of glucose (rCMRGl) were quantitatively analyzed in tumor lesions and the contralateral gray matter. Four patients with central neurocytoma underwent a complete PET study, including all circulatory and metabolic parameters; one patient was studied with 11C-methyl-L-methionine and FDG tracers. RESULTS: Tumor rCBF and rCBV were higher than comparable values in the contralateral gray matter in three of four patients. This high level of perfusion corresponds to angiographic findings that show intense tumor staining in tumors fed by perforated arteries. Tumor rOEF and rCMRO2 were significantly lower than corresponding values in the gray matter (rOEF, P < 0.01; rCMRO2, P < 0.05 by Student's t test). Tumor rCMRGl ranged from 2.68 to 6.26 mg/100 ml/minutes and did not exceed contralateral gray matter values in any of the five patients. Tumor rCMRGl was significantly lower (P < 0.02) than the gray matter rCMRGl. One tumor exhibited a relatively high value of rCMRGl (comparable to gray matter rCMRGl), and increased in size 4 months after partial resection. No other tumors appeared during postoperative follow-up periods that ranged from 4 to 135 months. CONCLUSIONS: Circulation and metabolism parameters measured by PET offer insight into the biologic characteristics of central neurocytoma. Tumor rCMRGl may be an indicator of the proliferating activity in central neurocytoma.

White matter hyperintensity in neurologically asymptomatic subjects.

Recent advances in magnetic resonance imaging (MRI) technology have had a great impact on the delectability of minute, asymptomatic lesions of the central nervous system. The clinical significance and treatment modes of these lesions, such as white matter hyperintensity (WMH) lesions detected by T2 MRI, remain controversial. To address these problems, we retrospectively evaluated WMH lesions in relation to clinical parameters for 240 neurologically asymptomatic persons who had visited a hospital for a medical check-up of the brain. Proton and T2-weighted MRI were obtained using a 0.5 T superconducting MR imager using the spin echo technique with a repetition time (TR) of 2800 msec. An echo delay times (TE) of 40 msec was used for the proton MRI, and a TE of 100 msec was used for the T2-weighted MRI. The images were visually analyzed according to a four-point grading system. The MRI findings were correlated with clinical parameters including age, gender, presenting symptoms, and hypertension. The overall frequency of WMH increased with age. Grades 2 and 3 of WMH were more frequent in aged persons, whereas the occurrence of grade 1 WMH remained relatively constant across age groups. Based on multiple regression analysis, age was the most significant variable influencing the frequency of WMH, followed by hypertension. These results imply that WMH lesions may simply be a phenomenon of aging, or may be an indicator of prepathologic state in an ischemic brain.

Laparoscopic retrieval of disconnected ventriculoperitoneal shunt catheters: report of two cases.

Two patients previously treated with ventriculoperitoneal shunt for hydrocephalus had the distal catheters disconnected, and they migrated to the free peritoneal cavity. The signs and symptoms of increased intracranial pressure occurred as a result of mechanical failure of the shunt system. Both patients successfully underwent a laparoscopic retrieval of the catheters using endoscopic grasping forceps, and revision of the ventriculoperitoneal shunt by inserting the new catheters into the peritoneal cavity was performed through a small entrance for the laparoscope. Recently, conventional laparotomy has been often replaced by laparoscopic surgery, and general surgeons are well familiar with the laparoscopic procedures. The significant advantage of this procedure is the ability to explore the entire peritoneal cavity for both diagnosis and treatment, and it is by far a less invasive approach than conventional laparotomy. The present report describes the laparoscopic procedure for removal of the migrated catheters and discusses its advantages over conventional laparotomy.