Surgical treatment for temporal lobe epilepsy in childhood]

We retrospectively analyzed 5 children (11-15 year) with intractable temporal lobe epilepsy (TLE) who underwent the anterior temporal lobectomy with hippocampectomy. Cases 1-3 had medial TLE (MTLE) with histologically verified hippocampal sclerosis, Case 4 had lateral TLE, and Case 5 had MTLE with old hemorrhagic lesion in the lateral temporal lobe. In Cases 3-5, chronic invasive electrocorticography recording using subdural electrodes was obtained, while in Cases 1 and 2, the epileptogenic region was defined by noninvasive preoperative evaluation. Postoperatively, Cases 1-3 became seizure free. All patients had psychosocial problems after the onset of their epilepsy, which was not improved even after the surgical control of epilepsy. Since most patients had morphological change and perfusional and metabolic disturbance outside the hippocampus at the time of surgery, earlier surgical consideration may be necessary.     

Metal artifacts reduction in computed tomography: A phantom study to compare the effectiveness of metal artifact reduction algorithm,model-based iterative reconstruction,and virtual monochromatic imaging

The purpose of this study was to compare the effectiveness of a metal artifact reduction algorithm (MAR), model-based iterative reconstruction (MBIR), and virtual monochromatic imaging (VMI) for reducing metal artifacts in CT imaging.A phantom study was performed for quantitatively evaluating the dark bands and fine streak artifacts generated by unilateral hip prostheses. Images were obtained by conventional scanning at 120 kilovolt peak, and reconstructed using filtered back projection, MAR, and MBIR. Furthermore, virtual monochromatic images (VMIs) at 70 kilo-electron volts (keV) and 140 keV with/without use of MAR were obtained by dual-energy CT. The extents and mean CT values of the dark bands and the differences in the standard deviations and location parameters of the fine streak artifacts evaluated by the Gumbel method in the images obtained by each of the methods were statistically compared by analyses of variance.Significant reduction of the extent of the dark bands was observed in the images reconstructed using MAR than in those not reconstructed using MAR (all, P < .01). Images obtained by VMI at 70 keV and 140 keV with use of MAR showed significantly increased mean CT values of the dark bands as compared to those obtained by reconstructions without use of MAR (all, <.01). Significant reduction of the difference in the standard deviations used to evaluate fine streak artifacts was observed in each of the image sets obtained with VMI at 140 keV with/without MAR and conventional CT with MBIR as compared to the images obtained using other methods (all, P < .05), except between VMI at 140 keV without MAR and conventional CT with MAR. The location parameter to evaluate fine streak artifacts was significantly reduced in CT images obtained using MBIR and in images obtained by VMI at 140 keV with/without MAR as compared to those obtained using other reconstruction methods (all, P < .01).In our present study, MAR appeared to be the most effective reconstruction method for reducing dark bands in CT images, and MBIR and VMI at 140 keV appeared to the most effective for reducing streak artifacts.     

Non-invasive gene delivery across the blood-brain barrier: present and future perspectives

<正>The aging of society has arrived,and is accompanied by an increase in the absolute numbers of patients with neurological disorders,such as Alzheimer’s and Parkinson’s diseases (Feigin et al., 2020).Such diseases,particularly Alzheimer’s disease and other forms of dementia,affect not only the patients themselves,but also the people around them,including family members and care givers.As a result,such neurological disorders are thought to carry a larger social burden compared to other dis...     

Sentinel Node Detection Method Using Contrast-Enhanced Ultrasonography with Sonazoid in Breast Cancer: Preliminary Clinical Study

This study aimed to evaluate the usefulness of sentinel lymph node (SLN) detection in breast cancer using contrast-enhanced ultrasonography (CEUS) with subareolar Sonazoid injection. The subjects were 20 breast cancer patients. General anesthesia was induced and 2 mL of Sonazoid was injected subareolarly. After massage of the injection site, the axillary area was observed transdermally using coded phase inversion harmonic ultrasonography with mechanical indices of 0.15 to 0.19. When contrast-enhanced lymph nodes (LNs) were seen, they were defined as CE-SLN. Two other SLN detection methods, the γ-probe-guided and dye-guided methods, were performed together. We evaluated the SLNs detected by each method to determine if they corresponded with each other and calculated the SLN detection rate. After the SLNs were resected, pathologic examinations were done. The SLN detection rate of the CEUS-guided method, the dye-guided method and the γ-probe-guided method were 70%, 75% and 100%, respectively. There was no statistically significant difference in these rates between the CEUS-guided and dye-guided methods (p = 0.99) but the CEUS-guided method showed a significantly lower rate than the γ-probe-guided method (p = 0.020), and dye-guided method also showed a significantly lower rate than the γ-probe-guided method (p = 0.047). The number of CE-SLNs was 1 or 2 (average 1.1) and each took 2 to 20 (average 5.3) min to detect. The CE-SLNs corresponded grossly with SLNs detected by the γ-probe-guided and dye-guided methods. The pathologic results indicated no metastasis from the resected SLNs in 15 of 20 cases. However, the CEUS-guided method detected 12 cases of these 15 and CE-SLNs were detected in two of the remaining five metastasis cases. In summary, in breast cancer patients, after subareolar injection of Sonazoid, contrast-enhanced LNs were observed in real time with ultrasonography. In an initial clinical study of 20 cases, the detection rate of the CEUS-guided method was less than that of the γ-probe-guided method. It is suggested that the CEUS-guided method using Sonazoid may, with some improvements, be a useful new modality for sentinel node identification. (E-mail: kiyoka@jichi.ac.jp)     

A case of systemic sclerosis with crescentic glomerulonephritis associated with perinuclear-antineutrophil cytoplasmic antibody (p-ANCA)]

A 50-year-old female with systemic sclerosis (SSc) developed rapidly progressive renal insufficiency. Laboratory findings showed rapid elevation of serum creatinine level (3.8 mg/dl) and a high titer of perinuclear-antineutrophil cytoplasmic antibody (p-ANCA) (504 EU/ml). Renal pathology revealed crescentic glomerulonephritis (CrGN) without mucoid intimal proliferation of the interlobal arteries and fibrinoid necrosis of the afferent arterioles, Immunofluorescent micrography showed focal segmental granular deposition of IgG and C 3 in the mesangium and along the capillary loop and was in agreement with pauci-immune type. Recently, a subtype of renal involvement in SSc that is associated exclusively with normotensive renal failure and recognizable by p-ANCA is suggested. On the other hand, SSc with p-ANCA-positive glomerulonephritis as this case can be considered to be overlap syndrome of SSc and microscopic polyangitis nodosa (microscopic PN) because in microscopic PN, p-ANCA is detected at the range of 50% to 80% and renal pathology reveals necrotizing glomerulonephritis. In this point, we may describe this case as a suggestive one about p-ANCA-positive glomerulonephritis.     

Development of a novel systemic gene delivery system for cancer therapy with a tumor-specific cleavable PEG-lipid

For successful cancer gene therapy via intravenous (i.v.) administration, it is essential to optimize the stability of carriers in the systemic circulation and the cellular association after the accumulation of the carrier in tumor tissue. However, a dilemma exists regarding the use of poly(ethylene glycol) (PEG), which is useful for conferring stability in the systemic circulation, but is undesirable for the cellular uptake and the following processes. We report the development of a PEG-peptide-lipid ternary conjugate (PEG-Peptide-DOPE conjugate (PPD)). In this strategy, the PEG is removed from the carriers via cleavage by a matrix metalloproteinase (MMP), which is specifically expressed in tumor tissues. An in vitro study revealed that the PPD-modified gene carrier (Multifunctional Envelope-type Nano Device: MEND) exhibited pDNA expression activity that was dependent on the MMP expression level in the host cells. In vivo studies further revealed that the PPD was potent in stabilizing MEND in the systemic circulation and facilitating tumor accumulation. Moreover, the i.v. administration of PPD or PEG/PPD dually-modified MEND resulted in the stimulation of pDNA expression in tumor tissue, as compared with a conventional PEG-modified MEND. Thus, MEND modified with PPD is a promising device, which has the potential to make in vivo cancer gene therapy achievable.     

Association of tumor necrosis factor receptor type II polymorphism 196R with Systemic lupus erythematosus in the Japanese: molecular and functional analysis.

OBJECTIVE: To investigate whether a polymorphism(s) or mutation(s) in the tumor necrosis factor receptor II (TNFRII) gene is involved in the pathogenesis of systemic lupus erythematosus (SLE). METHODS: All 10 exons of the TNFRII gene were analyzed by exon-specific polymerase chain reaction-single-strand conformation polymorphism, followed by nucleotide sequencing of exons that displayed aberrant bands. To analyze the function of the TNFRII polymorphisms, the full-length TNFRII complementary DNA of each allele was transfected in HeLa cells and then studied for specific binding of 125I-TNFalpha, as well as interleukin-6 (IL-6) production and cytotoxic activity after treatment with recombinant human TNFalpha. RESULTS: We identified 4 polymorphisms, at codons 56, 181, 196, and 232. The latter 2 had amino acid substitutions M196R and E232K, respectively. Only the 196R allele was significantly associated with SLE in our 105 Japanese SLE patients, with an allele frequency of 20.5%, compared with 12.6% in 99 healthy controls (P = 0.0335). More importantly, using TNFRII-transfected HeLa cells, we demonstrated significantly increased IL-6 production by 196R TNFRII compared with 196M TNFRII. The cytotoxic activity induced by 196R TNFRII was also increased compared with that of 196M TNFRII. This increase was achieved without affecting the binding affinity of TNFalpha to TNF-RII, as demonstrated by the finding that specific TNFalpha binding to the HeLa transfectants of 196R and 196M TNFRII was similar, with Kd values of 3.12 x 10(-10)M and 4.34 x 10(-10)M, respectively. CONCLUSION: These results suggest that 196R TNFRII, which transduces the signals of TNFalpha more effectively than does 196M TNFRII, is involved in the pathogenesis of SLE.     

Learning from the Viral Journey: How to Enter Cells and How to Overcome Intracellular Barriers to Reach the Nucleus

Viruses deliver their genome into host cells where they subsequently replicate and multiply. A variety of relevant strategies have evolved by which viruses gain intracellular access and utilize cellular machinery for the synthesis of their genome. Therefore, the viral journey provides insight into the cell’s trafficking machinery and how it can be best exploited to improve nonviral gene delivery systems. This review summarizes viral internalization pathways and intracellular trafficking of viruses, with an emphasis on the endosomal escape processes of nonenveloped viruses. Intracellular events from viral entry through nuclear delivery of the viral complementary DNA are also discussed.     

Tumor targeting of doxorubicin by anti-MT1-MMP antibody-modified PEG liposomes

Immunoliposomes are potent carriers for targeting of therapeutic drugs to specific cells. Membrane type-1 matrix metalloproteinase (MT1-MMP), which plays an important role in angiogenesis, is expressed on angiogenic endothelium cells as well as tumor cells. Then, the MT1-MMP might be useful as a target molecule for tumor and neovascularity. In the present study, we addressed a utility of antibodies against the MT1-MMP as a targeting ligand of liposomal anticancer drug. Fab' fragments of antibody against the MT1-MMP were modified at distal end of polyethylene glycol (PEG) of doxorubicin (DXR)-encapsulating liposomes, DXR-sterically stabilized immunoliposomes (DXR-SIL[anti-MT1-MMP(Fab')]). Modification with the antibody significantly enhanced cellular uptake of DXR-SIL[anti-MT1-MMP(Fab')] into the HT1080 cells, which highly express MT1-MMP, compared with the non-targeted liposomes (DXR-stealthliposomes (DXR-SL)), suggesting that MT1-MMP antibody (Fab') is a potent targeting ligand for the MT1-MMP expressed cells. In vivo systemic administration of DXR-SIL[anti-MT1-MMP(Fab')] into the tumor-bearing mice showed significant suppression of tumor growth compared to DXR-SL. This is presumably due to the active targeting of immunoliposomes for tumor and neovascularity. However, tumor accumulation of DXR-SIL[anti-MT1-MMP(Fab')] and DXR-SL were comparable, suggesting that both liposomal formulations accumulated in tumor via enhanced permeation and retention (EPR) effect, but not via targeting to the MT1-MMP expressed on both the endothelial and tumor cells. It appears that the enhanced antitumor activity of DXR-SIL[anti-MT1-MMP(Fab')] resulted from acceleration of cellular uptake of lioposomes owing to the incorporated antibody after extravasation from capillaries in tumor.