Flexion-distraction injuries in the thoracolumbar spine: an in vitro study of the relation between flexion angle and the motion axis of fracture

A new concept, the motion axis of fracture (MAF), which is defined as the transitional point from anterior compressive to posterior splitting failure on a lateral radiograph, has provided a true understanding of the mechanisms of flexion-distraction injuries in clinical cases. This study was designed to produce in vitro injuries that have MAFs and to clarify the relation between the flexion angle and the MAF location. Adolescent porcine thoracolumbar spines were exposed to a vertical compressive load to failure at three different flexion angles and then examined radiographically. The MAF location was recorded as the distance from the anterior border to the MAF expressed as a percentage of the anteroposterior diameter of the vertebral body. All specimens showed similar injuries, with MAFs consisting of anterior compression fractures in the vertebral bodies and posterior disruptions. A significant negative correlation emerged between the flexion angle and the MAF location (r = -0.890; p < 0.0001). These results suggest that even a vertical compressive load contributes to the production of a flexion-distraction injury with an MAF in the thoracolumbar spine. They also indicate that the flexion angle of the spine at which the vertical compressive load is applied is an important factor in determining the MAF location; that is, the larger the flexion angle, the more anterior the MAF.     

Involvement of transporters in the hepatic uptake and biliary excretion of valsartan, a selective antagonist of the angiotensin II AT1-receptor, in humans.

Valsartan is a highly selective angiotensin II AT1-receptor antagonist for the treatment of hypertension. Valsartan is mainly excreted into the bile in unchanged form. Because valsartan has an anionic carboxyl group, we hypothesized that a series of organic anion transporters could be involved in its hepatic clearance. In this study, to identify transporters that mediate the hepatic uptake and biliary excretion of valsartan and estimate the contribution of each transporter to the overall hepatic uptake and efflux, we characterized its transport using transporter-expressing systems, human cryopreserved hepatocytes, and Mrp2-deficient Eisai hyperbilirubinemic rats (EHBRs). Valsartan was significantly taken up into organic anion-transporting polypeptide (OATP) 1B1 (OATP2/OATP-C)- and OATP1B3 (OATP8)-expressing HEK293 cells. We also observed saturable uptake into human hepatocytes. Based on our estimation, the relative contribution of OATP1B1 to the uptake of valsartan in human hepatocytes depends on the batch, ranging from 20 to 70%. Regarding efflux transporters, the ratio of basal-to-apical transcellular transport of valsartan to that in the opposite direction in OATP1B1/MRP2 (multidrug resistance-associated protein 2) double transfected cells was the highest among the three kinds of double transfectants, OATP1B1/MRP2, OATP1B1/multi-drug resistance 1, and OATP1B1/breast cancer resistance protein-expressing MDCKII cells. We observed saturable ATP-dependent transport into membrane vesicles expressing human MRP2. We also found that the elimination of intravenously administered valsartan from plasma was markedly delayed, and the biliary excretion was severely impaired in EHBR compared with normal Sprague-Dawley rats. These results suggest that OATP1B1 and OATP1B3 as the uptake transporters and MRP2 as the efflux transporter are responsible for the efficient hepatobiliary transport of valsartan.     

Immunohistochemical Study of Serum Proteins in Normal and Cadmium-Treated Mouse Testis by in vivo CryotechniqueImmunohistochemical Study of Serum Proteins in Normal and Cadmium-Treated Mouse Testis by in vivo Cryotechnique

Objective To investigate time-dependent changes of serum proteins permeability in the normal and cadmium（Cd）-treated mouse testis, reflecting tight junctional （TJ） barriers of Sertoli cells Methods The serum proteins, albumin and immunoglobulin-G（IgG）, in the seminiferous tubules were firstly immobilized by the “in vivo cryotechnique”, in which the dynamic blood circulation was always kept. The cryofixed testicular tissues were then processed for the freeze-substitution method, and embedded in the paraffin wax. Serial sections of 5μm thickness were immunostained by anti-mouse albumin or IgG antibody with peroxidase immunostaining, and also stained with hematoxylin-eosine （HE）for morphological observation. Results In normal seminiferous tubules, albumin immunoreaction products were localized around peritubular myoid cells and among Leydig cells, as well as in blood vessels. They were also localized as arch-like patterns around some spermatogonia in basal compartments. The number of the immunopositive arch structures was different according to developmental stages of the seminiferous cycle, judging from the arrangement of germ cells by HE-staining. The patterns of localization of IgG immunostaining in normal mouse testis were similar to that of albumin. In 24 h after Cd-treatment, some enlarged spaces and vesicular formation in the seminiferous epithelium were observed on the paraffin sections by HE-staining. The albumin or IgGimmunolocalization was seen not only in the basal compartments, but also in the adluminal compartments between Sertoli.cells and germ cells. Conclusion The structural changes of inter-Sertoli TJ barriers in vivo, such as different immunostaining patterns of serum proteins between the normal and Cd-treated mouse seminiferous tubules, could be clearly detected by the “in vivo cryotechnique” with albumin or IgG immunohistochemistry.     

Acute aortic dissection with new massive cerebral infarction - a successful repair with ligature of the right common carotid artery.

It remains unclear whether or not the infarcted brain caused by aortic dissection should be reperfused when an emergency operation is needed for aortic arch dissection. A 64-year-old woman presented with severe back pain and syncope with a sudden left hemiplegia. CT scan demonstrated an aortic dissection of the entire aorta, obstruction of the right common carotid artery by extended aortic dissection, cerebral infarction of the right middle cerebral artery territory, brain edema and pericardial effusion. Though she was unable to communicate with us, she underwent an emergent aortic arch replacement and ligature of the right common carotid artery nine hours after the onset of stroke, when massive cerebral infarction was established. She survived the operation and regained full consciousness. When brain infarction was established by extended aortic dissection in emergent aortic surgery, concomitant ligature of the responsible artery to the brain infarction may be allowed for avoiding cerebral damage leading to brain death.     

Tuberculosis of the tongue. A case report with immunologic study.

A case of tuberculosis of the tongue in a 59-year-old woman with active pulmonary tuberculosis is described. The lingual tuberculosis was considered to be a secondary infection from the pulmonary disease, but the oral lesions were, in fact, noticed prior to recognition of the pulmonary lesion. This case was marked by a multiplicity or oral lesions arising on the bilateral surfaces of the tongue. Immunologic investigation revealed that cell-mediated immune responses in the patient were within the normal range in terms of the PPD skin test, DNCB skin test, lymphocyte transformation test, and subpopulation of the peripheral blood lymphocytes. Rosette-forming assay on the frozen sections disclosed that T-lymphocytes and macrophages were predominant in the lymphoid cells infiltrating the tuberculous lesion.     

Loss of p21WAF1/CIP1 expression in invasive fronts of oral tongue squamous cell carcinomas is correlated with tumor progression and poor prognosis

The clinicopathological significance of cell-cycle proteins has remained unclear in oral tongue squamous cell carcinomas (OTSCC). In the current study, we evaluated several cell-cycle proteins in relation to clinicopathological parameters and disease outcome for OTSCC. A total of 123 previously untreated patients with OTSCC, who underwent surgical treatment, were enrolled. Tumor specimens were examined for expression of p21, p27, p16, p53, and p63 using immunohistochemistry, with reference to clinicopathological factors and disease outcome. It is noteworthy that differences in p21 immunoreactivity were evident between the shallow region and invasive front of tumors within the same specimens. Loss of p21 expression in invasive fronts was found to be associated with clinicopathological factors of tumor progression and poor prognosis. p21 expression in invasive fronts is a significant indicator for impact on survival. Moreover, p21 is one of the important factors that regulate the progression of malignant cells in OTSCC.     

The modifier subunit of glutamate cysteine ligase relates to cisplatin resistance in human small cell lung cancer xenografts in vivo

Glutamate cysteine ligase (GCL) plays an important role in the intracellular detoxification of cisplatin (CDDP). GCL is composed of a modifier or light chain subunit (GCLM) and a catalytic or heavy chain subunit (GCLC). Previously, we showed that the GCL subunits enhanced CDDP-resistance in non-small cell lung cancer (NSCLC) xenografts. In small cell lung cancer (SCLC), it is unclear whether the GCL subunits are essential to CDDP-resistance. We examined the gene expression of GCLM and GCLC in four human SCLC xenografts with the real-time polymerase chain reaction (PCR). An in vivo drug sensitivity test with CDDP was performed on the SCLC xenografts. CDDP-resistance was examined as the growth ratio of the relative volume of the treated xenografts to the controls (T/C%). The expression level of GCLM gene in SCLC was significantly lower than that in NSCLC (p=0.0026, Welch's t-test). One of four SCLC xenografts showed 62% of T/C and this was evaluated as CDDP-resistance, while the other three xenografts were sensitive to CDDP in vivo (Mann-Whitney U-test, p<0.01, one-sided). The expression level of the GCLM gene was significantly correlated to T/C% (Fisher's test, p=0.0289, correlations = 0.975), while the GCLC gene expression level was not associated with T/C%. These results suggest that the overexpression of GCLM is correlated with CDDP-resistance in SCLC xenografts in vivo.     

Idiopathic thrombocytopenic purpura and myasthenia gravis after fludarabine treatment for chronic lymphocytic leukemia

We report a patient with chronic lymphocytic leukemia (CLL) who developed idiopathic thrombocytopenic purpura (ITP) and myasthenia gravis (MG) after fludarabine therapy. ITP developed after 6 cycles of fludarabine treatment, and MG occurred 2 months after the onset of ITP. MG was successfully treated with immunosuppressive therapy and plasma exchange, while rituximab was effective for CLL and ITP. Fludarabine seemed to have an important role in the onset of ITP and MG in this case.