Shift of motor activation areas during recovery from hemiparesis after cerebral infarction: a longitudinal study with near-infrared spectroscopy

Motor functional recovery after stroke may be attributable to cerebral reorganization. We used near-infrared spectroscopy, which measures non-invasively the changes in oxy- and deoxy-hemoglobin concentrations in response to neural activation, for monitoring cerebral activation in stroke patients, and investigated the longitudinal changes in functional laterality of activations in the primary sensorimotor cortex during unilateral audio-paced (1 Hz) hand movement. We examined five ischemic stroke patients (4 females and 1 male, 52-67 years old) with mild to moderate hemiparesis at acute stages and chronic stages at least 1 month later. Normal subjects (3 females and 2 males, 47-63 years old) were also included. Unilateral hand movement activated predominantly the contralateral primary sensorimotor cortex in the normal subjects and the stroke patients when they moved unaffected hand. Affected hand movements activated bilateral sensorimotor cortices early after stroke (< 25 days of stroke onset), whereas the activation pattern returned toward normal at later periods (> 35 days). The contralaterality index (0.34 +/- 0.12 in normal control) was reduced at early periods (0.00 +/- 0.03, p < 0.01) after stroke, and returned to normal (0.35 +/- 0.24) as motor function recovered. These findings suggest that a transient increase in motor activation in the ipsilateral intact hemisphere within 1 month may play an important role in the recovery from motor dysfunction after stroke.     

BPOZ-2 directly binds to eEF1A1 to promote eEF1A1 ubiquitylation and degradation and prevent translation

Bood POZ containing gene type 2 (BPOZ-2), which contains ankyrin repeats, NLS, BTB/POZ domains and LXXLL motifs, is an adaptor protein for the E3 ubiquitin ligase scaffold protein CUL3. We isolated a cDNA encoding eukaryotic elongation factor 1A1 (eEF1A1) as a BPOZ-2 binding protein by screening a human thymus cDNA library using a yeast two-hybrid system. eEF1A1 is essential for translation and is also involved in the 26S proteasome-dependent degradation of misfolded or unfolded proteins. The binding between BPOZ-2 and eEF1A1 was confirmed by pull-down and immunoprecipitation assays in vitro and in vivo , respectively. BPOZ-2 binds to eEF1A1 through the ankyrin repeats and both BTB/POZ domains in BPOZ-2 and Domains I and III in eEF1A1. BPOZ-2 and eEF1A1 over-expressed in HEK 293T cells co-localized as speckles within the cytoplasm. BPOZ-2 promoted eEF1A1 ubiquitylation and degradation, suggesting that eEF1A1 is a substrate of BPOZ-2. BPOZ-2 inhibited GTP binding to eEF1A1 and prevented translation in in vitro translation assay using rabbit reticulocytes.     

Bone turnover markers correlate with implant fixation in a rat model using LPS-doped particles to induced implant loosening

Revision surgery for particle-induced implant loosening in total joint replacement is expected to increase dramatically over the next few decades. This study was designed to investigate if local tissue and serum markers of bone remodeling reflect implant fixation following administration of lipopolysaccharide (LPS)-doped polyethylene (PE) particles in a rat model. Twenty-four rats received bilateral implantation of intramedullary titanium rods in the distal femur, followed by weekly bilateral intra-articular injection of either LPS-doped PE particles (n = 12) or vehicle that contained no particles (n = 12) for 12 weeks. The group in which the particles were injected had increased serum C-terminal telopeptide of type I collagen (CTX-I), decreased serum osteocalcin (OC), increased peri-implant eroded surface, decreased peri-implant bone volume, and decreased mechanical pull-out strength compared to the controls. Implant fixation strength was positively correlated with peri-implant bone volume and serum OC and inversely correlated with serum CTX-I, while energy to yield was positively correlated with serum OC and inversely correlated with the number of tartrate-resistant acid phosphatase positive cells at the interface and the amount of peri-implant eroded surface. There was no effect on trabecular bone volume at a remote site. Thus, the particle-induced impaired fixation in this rat model was directly associated with local and serum markers of elevated bone resorption and depressed bone formation, supporting the rationale of exploring both anticatabolic and anabolic strategies to treat and prevent particle-related implant osteolysis and loosening, and indicating that serum markers may prove useful in tracking implant fixation.     

The effect of superficial chemistry of titanium on osteoblastic function

The surface topography and chemistry of titanium are postulated to be two major factors that affect the osseointegration capacity of titanium implants. However, it is extremely difficult to control one factor without changing the other, which prevents the isolation of the genuine effect of one factor. This study aimed to determine whether surface chemistry of titanium alone affects osteoblastic function. Two different titanium surfaces were prepared by sputter depositioning of titanium (Ti; 99.99% purity) or titanium dioxide (TiO2; 99.99% purity) (50-nm thick for each) onto machined commercially pure titanium disks. Rat bone marrow-derived osteoblastic cells were cultured on each of the two surfaces. TiO2 surface showed 4.4 times higher elemental oxygen concentration and higher water wettability than Ti surface. Scanning electron microscopic and atomic force microscopic examination revealed no differences in surface topography and roughness values between the two surfaces. The cell proliferated more on TiO2 than on Ti by up to 60%. Although the expression of collagen I gene increased more rapidly on TiO2 at early culture stage of day 3, the late stage marker genes for osteoblastic differentiation, including osteopontin and osteocalcin, were not modulated between the two cultures. The alkaline phosphatase positive area and mineralized nodule area were approximately two times larger on TiO2 than on Ti. In conclusion, titanium materials having different superficial chemistry, that is, titanium or titanium dioxide, may exert different biological capacity of osteoblasts; titanium dioxide may induce superior osteoconduction, primarily because of the increased osteoblastic proliferation.     

Caenorhabditis elegans Rab escort protein (REP‐1) differently regulates each Rab protein function and localization in a tissue‐dependent manner

Rab proteins play a critical role in intracellular vesicle trafficking and require post‐translational modification by adding lipids at the C‐terminus for proper functions. This modification is preceded by the formation of a trimeric protein complex with the Rab escort protein (REP) and the Rab geranylgeranyltransferase (RabGGTase). However, the genetic hierarchy among these proteins and the tissue‐specificity of each protein function are not yet clearly understood. Here we identified the Caenorhabditis elegans rep‐1 gene and found that a rep‐1 mutant showed a mild defect in synaptic transmission and defecation behaviors. Genetic analyses using the exocytic Rab mutants rab‐3 or rab‐27 suggested that rep‐1 functions only in the RAB‐27 pathway, and not in the RAB‐3 pathway, for synaptic transmission at neuromuscular junctions. However, the disruption of REP‐1 did not cause defecation defects compared to severe defects in either RAB‐27 or RabGGTase disruption, suggesting that REP‐1 is not essential for RAB‐27 signaling in defection. Some Rab proteins did not physically interact with REP‐1, and localization of these Rab proteins was not severely affected by REP‐1 disruption. These findings suggest that REP‐1 functions are required in specific Rab pathways and in specific tissues, and that some Rab proteins are functionally prenylated without REP‐1.     

Clinical significance of expression of membrane type 1 matrix metalloproteinase and matrix metalloproteinase-2 in human head and neck squamous cell carcinoma

Three different membrane-type matrix metalloproteinases (MT-MMPs) activate in vitro the latent form of matrix metalloproteinase-2 (MMP-2), which is one of the key proteinases in invasion and metastasis of various cancers. We examined the mRNA expression of MT1, 2, and 3-MMPs and MMP-2 in cell lines of head and neck squamous cell carcinoma (HNSCC) and quantitated the relative expression levels in human HNSCC tissues by Northern blotting. The tissue localization of MT1-MMP and MMP-2 was determined by immunohistochemistry and in situ hybridization. Their implications in clinicopathologic factors were statistically evaluated. All cell lines examined consistently expressed MT1-MMP and MMP-2, but not MT2, 3-MMP. In the clinical specimens, there was a significant correlation in coexpression of messenger of RNA (P = .0005) and colocalization by immunohistochemistry (P < .0001) for MT1-MMP and MMP-2. Relative mRNA expression levels of MT1-MMP and MMP-2 in the carcinoma tissues were significantly higher than those of the control tissues (P = .0045 and P = .0122, respectively). Both mRNA expression level and immunopositivity of MT1-MMP significantly correlated with lymph node metastasis (P = .0081 and P = .0193, respectively), which was confirmed by multivariate logistic regression analysis. Immunoreaction of MT1-MMP and its mRNA expression were observed in both carcinoma cells and stromal cells. The localization of MMP-2 closely corresponded to that of MT1-MMP. These observations suggest that MT1-MMP possesses a role as a determinant of lymph node metastasis in HNSCC, and that concurrent expression of MT1-MMP and MMP-2 are involved in progression of HNSCC.     

Phenotype Analysis and Quantification of Proliferating Cells in the Cortical Gray Matter of the Adult Rat

In intact adult mammalian brains, there are two neurogenic regions: the subependymal zone and the subgranular layer of the hippocampus. Even outside these regions, small numbers of proliferating precursors do exist. Many studies suggest that the majority of these are oligodendrocyte precursors that express NG2, a chondroitin sulfate proteoglycan, and most of the residual proliferating cells seem to be endothelial cells. However, it is still unclear whether NG2-immunonegative proliferating precursors are present, because previous studies have neglected their possible existence. In this study, we systematically analyzed the phenotypes of the proliferating cells in the intact adult rat cortical gray matter. We improved our techniques and carefully characterized the proliferating cells, because there were several problems with identifying and quantifying the proliferating cells: the detection of NG2-expressing cells was dependent on the fixation condition; there were residual proliferating leukocytes in the blood vessels; and two anti-NG2 antibodies gave rise to different staining patterns. Moreover, we used two methods, BrdU and Ki67 immunostaining, to quantify the proliferating cells. Our results strongly suggest that in the intact adult cerebral cortical gray matter, there were only two types of proliferating cells: the majority were NG2-expressing cells, including pericytes, and the rest were endothelial cells.     

Stercoral perforation of the colon during pregnancy

A 39-year-old Japanese woman was referred to our hospital for severe abdominal pain at 22 weeks and 2 days of gestation. Abdominal computed tomography (CT) suggested perforation of the gastrointestinal tract and emergency surgery was conducted. There was a fibrous adhesion between an enlarged uterus and the sigmoid colon. There was a 5.0-cm perforation near the adhesion in the posterior wall of the sigmoid colon. We performed a partial resection of the sigmoid colon and Hartmann's procedure with copious intraperitoneal lavage. Five hours following the laparotomy, uterine contractions could not be controlled and the patient delivered vaginally. The neonate died almost immediately after delivery. We conclude that although stercoral bowel perforation is rare, poor prognosis after perforation emphasizes the need to carry out a CT scan for patients who present with undiagnosed severe abdominal pain and compatible medical history, even if the patient is pregnant.     

The suprascapular notch narrows with aging: a preliminary solution of the old conjecture based on a 3D-CT evaluation

Purpose

The purpose of this study was to describe the morphology of the suprascapular notch in terms of age distribution. We hypothesized that the notch narrows with aging.

Methods

Seven hundred and sixty consecutive patients (465 men and 295 women) scheduled for a shoulder surgery were retrospectively reviewed. A 3D-CT of the shoulder was taken to evaluate the shape of the notch according to the Rengachary classification. The six types of Rengachary classification were arranged into three major categories according to transverse scapular ligament ossification and notch size as follows: the wide notch (type 1 and type 2); the narrow notch (type 3 and type 4); and the ossified notch (type 5 and type 6). Comparisons between categories were done with a one-way analysis of variance.

Results

There was a statistically significant difference among the three categories (P < .01): the narrow notch group (n = 442, 63.4 ± 12.8 years) and the ossified notch group (n = 66, 65.9 ± 10.6 years) were significantly older than the wide notch group (n = 252, 57.5 ± 17.8 years), respectively. In patients with Rengachary type 5 shoulders, ossification was dominant on the medial side of the notch in 37 of 39 shoulders (92.3 %).

Conclusion

The current study showed that morphological changes of the scapular notch are related to aging. The narrow notch and the ossified notch are seemed to be developed from the wide notch in terms of the ossification starting from the medial side.