A missense mutation in the proteolipid protein gene responsible for Pelizaeus--Merzbacher disease in a Japanese family

We investigated the proteolipid protein (PLP) gene of two boysin a Japanese family with Pelizaeus—Merzbacher disease(PMD), an X-linked neurologic disorder characterized by dysmyelinationin the central nervous system (CNS). The patients showed similarclinical signs from birth and autopsy on the elder brother confirmeda connatal type of PMD. Direct sequencing of the PLP gene andPLP mRNAs from the brain of the PMD patient revealed a G toT transition in exon V of the PLP gene, which leads to a glycineto cystein substitution at residue 220. Allele-specific oligonucleotidehybridization revealed that this mutation was also present inhis brother, but was absent in 100 X chromosomes of normal Japaneseindividuals. Northern blot analysis showed that the mRNA levelsof PLP and myelin basic protein, two major myelin proteins producedby oligodendrocytes, were much reduced in the PMD brain, hence,there was a specific loss of oligodendrocytes. It seems likelythat the substitution is responsible for PMD (connatal type)in this particular family and causes oligodendrocytes deathin the CNS.     

Interaction of rat ascites hepatoma cells with cultured mesothelial cell layers: a model for tumor invasion

Interactions of rat ascites hepatoma cells with primary cultured layers of rat mesentery-derived cells were studied. The mesentery-derived cells were isolated from rat mesentery and cultured in Eagle's minimum essential medium with a 2-fold concentration of amino acids and vitamins supplemented with 10% calf serum. The primary cultured cells, consisting mainly of mesothelial cells in polygonal shape, forms a "paving stone" sheet. Upon seeding the tumor cells on the mesentery-derived cell layers, three different types of tumor cell growth were observed. Type 1 was the formation of piled-up tumor cell nests on mesothelial cell layers. Type 2 was the formation of flattened tumor cell islands underneath mesothelial cell layers. This island formation was clearly observed under a phase contrast microscope 2 days after the tumor cell seeding. Protrusion of cellular processes of the tumor cells beneath mesothelial cells was occasionally seen. Type 3 was the growth of tumor cells in suspension. These types of tumor cell growth closely resemble those in the peritoneal cavity observed after i.p. implantation of the tumor cells. When the tumor cells recovered from the blood of tumor-bearing rats were seeded, flattened tumor cell islands were formed 15 times more frequently than when the tumor cells isolated from host peritoneal cavity were seeded. Shortly after the appearance of small flattened tumor cell islands, a distinct morphological change of mesothelial cells from polygonal to spindle shape was seen preferentially at the marginal area of the cell layers (a partial retraction of cell edges). The retraction of mesothelial cells was induced not only by seeding the tumor cells but by adding the tumor ascites fluid or the medium conditioned by the tumor cell culture. The morphological change was reversed by changing the culture medium to remove the effectors. These results indicate that the system described in this study can provide a useful model to study tumor cell invasion.     

Pre-operative higher hematocrit and lower total protein levels are independent risk factors for cerebral hyperperfusion syndrome after superficial temporal artery–middle cerebral artery anastomosis with pial synangiosis in adult moyamoya disease patients—case-control study

Neurosurgical Review - Superficial temporal artery (STA)–middle cerebral artery (MCA) anastomosis is a standard treatment for adult moyamoya disease (MMD) patients. Cerebral hyperperfusion...     

Diagnostic impact of monitoring transcranial motor-evoked potentials to prevent ischemic complications during endovascular treatment for intracranial aneurysms

Neurosurgical Review - The present study aimed to determine the incidence of intraprocedural motor-evoked potential (MEP) changes and to correlate them with intraprocedural ischemic complications...     

Clinical Outcome of Cytoreductive Surgery Prior to Bevacizumab for Patients with Recurrent Glioblastoma: A Single-center Retrospective Analysis

Bevacizumab (BEV) is a key anti-angiogenic agent used in the treatment for recurrent glioblastoma multiforme (GBM). The aim of this study was to investigate whether cytoreductive surgery prior to treatment with BEV contributes to prolongation of survival for patients with recurrent GBM. We retrospectively analyzed the treatment outcomes of 124 patients with recurrent GBM who were initially treated with the Stupp protocol between 2006 and 2019. Given that BEV has only been available in Japan since 2013, we grouped the patients into two groups according to the time of first recurrence: the pre-BEV group (N = 51) included patients who had recurrence before BEV approval, and the BEV group (N = 73) included patients with recurrence after BEV approval. The overall survival after first recurrence (OS-R) was analyzed according to the treatment strategy. Among 124 patients, 27 patients (19.4%) received cytoreductive surgery. There were nine cases in the pre-BEV group and 18 cases in the BEV group. Although the mean extent of resection for both groups was almost equal, OS-R was significantly different. The median OS-R was 8.1 m in the pre-BEV group and 16.3 m in the BEV group (P = 0.007). Multivariate analysis revealed that the unavailability of BEV postoperatively (P = 0.03) and decreasing performance status by surgery (P = 0.01) were significant poor prognostic factors for survival after surgery. With the advent of BEV, cytoreductive surgery might provide superior survival benefit at the time of GBM recurrence, especially in cases where surgery can be performed without deteriorating the patient’s condition.     

Clinical results of arthroscopic rotator cuff repair in diabetic and non-diabetic patients

BackgroundAlthough the clinical outcomes of arthroscopic rotator cuff repair (ARCR) have been reported, few studies have focused on diabetic patients. We investigated and compared the clinical results of ARCR in patients with and without diabetes.MethodsThis retrospective study involved 195 consecutive patients who underwent ARCR from 2015 to 2018 in our hospital. Twenty-seven and 168 shoulders were assigned to diabetes and non-diabetes groups, respectively. Diabetic patients with poor control were preoperatively hospitalized for perioperative diabetic control. We evaluated range of motion (ROM), Japanese Orthopaedic Association shoulder (JOA) score, Constant Shoulder Score, and University of California, Los Angeles (UCLA) score preoperatively and at 6 months and 1 year post-ARCR. Rates of rotator cuff retear 1 year post-ARCR and preoperative and postoperative stiff shoulder were also evaluated. We compared the results between groups and analyzed them statistically. A p-value of <0.05 was considered statistically significant.ResultsPreoperative ROM, JOA score, Constant Shoulder Score and UCLA scores showed significant improvement at post-ARCR in both groups (p < 0.05). On comparing the groups, although preoperative JOA score and Constant Shoulder Score were significantly lower in diabetes group than in non-diabetes group (diabetic/non-diabetic group; 60.0/65.3 for JOA score; p = 0.003, 59.7/64.2 for Constant Shoulder Score; p = 0.003), there was no significant difference postoperatively (6 months post-ARCR; 88.0/89.7 for JOA score; p = 0.783, 88.1/88.6 for Constant Shoulder Score; p = 0.597, 1 year post-ARCR; 96.7/95.4 for JOA score; p = 0.238, 96.6/95.4 for Constant Shoulder Score; p = 0.248). Furthermore, preoperative and postoperative stiff shoulder and retear rates were not significantly different between groups (p = 0.152, p = 0.344, p = 0.347, and p = 0.563, respectively).ConclusionDiabetic patients showed comparable clinical results with non-diabetic patients post-ARCR. Perioperative diabetic control may be recommended for preoperatively uncontrolled diabetic patients.     

Knee Flexion Angle Following Total Knee Arthroplasty Relates to a Preoperative Range of Motion of the Hip

BackgroundMany factors have been reported to affect postoperative range of knee flexion after total knee arthroplasty (TKA); however, no study has reported the impact of preoperative range of motion of the hip to the postoperative flexion angle of the knee thus far.MethodsOf 38 consecutive patients who underwent posterior-stabilized TKA, we assessed 21 patients after excluding 17 patients who met exclusion criteria. The range of motion of the knee and the hip, age, body-mass index, serum albumin level, HbA1c, Kellgren–Lawrence grade, knee extension strength and radiological femorotibial angle as well as postoperative knee flexion angle at three months were evaluated. The preoperative data and the knee flexion angle at three months after TKA were compared using Spearman''s rank correlation coefficient.ResultsKnee flexion angle at three months after TKA was positively correlated with preoperative flexion (ρ = 0.616, p = 0.007) and external rotation angle (ρ = 0.576, p = 0.012) of the hip as well as preoperative knee flexion angle (ρ = 0.797, p = 0.001). There were no correlations between postoperative knee flexion angle and other preoperative data.ConclusionsPatients with restricted flexion and/or external rotation of the hip may have contractures of Gluteus maximus, Gluteus medius and Tensor fasciae latae, which can cause hypertension of iliotibial tract. It may cause decreased internal rotation of the tibia when the knee is flexed, which affects postoperative knee flexion angle, thus limited flexion and/or external rotation of the hip might restrict knee flexion angle following TKA.     

Nomograms predicting extra- and early intrahepatic recurrence after hepatic resection of hepatocellular carcinoma

BackgroundExtrahepatic recurrence and early intrahepatic recurrence of hepatocellular carcinoma after hepatic resection are indicative of poor prognoses. We aimed to develop nomograms to predict extrahepatic recurrence and early intrahepatic recurrence after hepatic resection.MethodsThe participants of this study were 1,206 patients who underwent initial and curative hepatic resection for hepatocellular carcinoma. Multivariate logistic regression analyses using the Akaike information criterion were used to construct nomograms to predict extrahepatic recurrence and early intrahepatic recurrence (within 1 year of surgery) at the first recurrence sites after hepatic resection. Performance of each nomogram was evaluated by calibration plots with bootstrapping.ResultsExtrahepatic recurrence was identified in 95 patients (7.9%) and early intrahepatic recurrence in 296 patients (24.5%). Three predictive factors, α-fetoprotein >200 ng/mL, tumor size (3–5 cm or >5 cm vs ≤3 cm), and image-diagnosed venous invasion by computed tomography, were adopted in the final model of the extrahepatic recurrence nomogram with a concordance index of 0.75. Tumor size and 2 additional predictors (ie, multiple tumors and image-diagnosed portal invasion) were adopted in the final model of the early intrahepatic recurrence nomogram with a concordance index of 0.67. The calibration plots showed good agreement between the nomogram predictions of extrahepatic recurrence and early intrahepatic recurrence and the actual observations of extrahepatic recurrence and early intrahepatic recurrence, respectively.ConclusionWe have developed reliable nomograms to predict extrahepatic recurrence and early intrahepatic recurrence of hepatocellular carcinoma after hepatic resection. These are useful for the diagnostic prediction of extrahepatic recurrence and early intrahepatic recurrence and could guide the surgeon’s selection of treatment strategies for hepatocellular carcinoma patients.     

Distinctions between microglial cells and peripheral macrophages with regard to adhesive activities and morphology.

Activated microglial cells and peripheral macrophages are hardly distinguishable from the viewpoints of morphology and function. There are various immunological markers common to both microglial cells and peripheral macrophages. In the present study, however, we found that microglial cells have distinct characters in terms of adhesion and morphology. By using a "rheoscope," that is an apparatus to rheologically measure the strength of cell adhesion to substrates, rat microglial cells were found to attach to polystyrene dishes much more weakly than alveolar and peritoneal macrophages. Interferon-gamma (IFNgamma) strengthened the adhesion of alveolar and peritoneal macrophages, whereas it weakened that of microglial cells. Morphological changes of microglial cells induced by IFNgamma were also different from those of peripheral macrophages. Furthermore, alveolar and peritoneal macrophages produced NO in response to IFNgamma, while microglial cells did not. When cultured on astrocyte-derived extracellular matrix (AsECM) in serum-free medium, only microglial cells extended multiple ramified processes. Conversely, alveolar and peritoneal macrophages on AsECM shrunk their ruffling membrane and rounded up. These distinctions between microglial cells and macrophages may reflect differences in cell lineages as well as environments in which individual cells reside.     

No ethnic difference between Caucasian and Japanese hepatic samples in the expression frequency of CYP3A5 and CYP3A7 proteins

Ethnic differences in the pharmacokinetics of nifedipine, a substrate of CYP3A, and in CYP3A7 expression have been reported. The aim of the present study was to measure the protein levels of CYP3A4, CYP3A5, and CYP3A7 and nifedipine oxidation activity in hepatic microsomes from 15 Caucasian and 15 Japanese patients for comparison between the two ethnic groups. Nifedipine oxidation activity and CYP3A4 protein level were well correlated. No significant difference between Caucasian and Japanese microsomal samples was found in nifedipine oxidation activity or in the CYP3A4 protein level. CYP3A5 was detected in 6 of 15 Caucasian samples and in 5 of 15 Japanese samples, but no ethnic difference was found in either the frequency of expression or its protein level. CYP3A7 was found in 10 of 15 Caucasian samples and in 14 of 15 Japanese samples. Although the estimated CYP3A7 protein level was higher in the Japanese than in the Caucasian samples, its protein level was much lower than that of CYP3A4. These results imply that the contribution of CYP3A5 or CYP3A7 to the purported Caucasian-Japanese ethnic difference in the overall CYP3A activity seems to be small.