Antibodies to potassium channels pc12 in serum of Isaacs' syndrome: Western blot and immunohistochemical studies

We investigated the pathophysiology of nerve hyperexcitability in a patient with Isaacs' syndrome, who had typical clinical and electromyographic features and responded to plasma exchange. Immunoblotting and immunohistochemistry studies showed that antibodies from this patient reacted with the lysate at a neuronal cell line (PC12). In Western blots, constituents of the patient's serum, particularly immunoglobulin M, reacted with proteins of approximately 50 and 18 kDa, whereas the control serum did not. A cross-linking study with alpha-dendrotoxin (7 kDa) showed a 57 kDa protein-peptide complex. Immunohistochemistry showed that the patient's serum reacted with PC12 cells and human intramuscular nerve axons. Our findings indicate that in Isaac's syndrome nerve hyperexcitability is the result of the immunological involvement of the voltage-dependent potassium channels located along the distal motor nerve or at the nerve terminal. © 1997 John Wiley & Sons, Inc. Muscle Nerve, 20, 299–305, 1997.     

B7-1-transfected tumor vaccine counteracts chemotherapy-induced immunosuppression and prolongs the survival of rats bearing highly metastatic osteosarcoma cells

To investigate the therapeutic efficacy of B7-1-expressing tumor vaccine on metastatic osteosarcoma, we introduced mouse B7-1 cDNA into a rat osteosarcoma cell line, MSK-8G. Flow cytometric analysis confirmed that the transfectants designated as B7-1-8G 10-1 and B7-1-8G 15-5 stably expressed B7-1 molecules on the cell surface. B7-1 transfectants were not only rejected by immunocompetent F344 rats but also conferred systemic immunity that protected against challenge with B7-negative parental osteosarcoma cells. In contrast, T-cell-deficient nude rats failed to reject B7-1 transfectants, indicating that T cells play a major role in the development of systemic immunity. We then conducted experimental therapies using irradiated B7-1-transfected tumor vaccine and methotrexate in an orthotopic implantation model. B7-1-transfected tumor vaccine significantly reduced the number of pulmonary metastatic nodules. Moreover, the combination of methotrexate and tumor vaccine further decreased the number of pulmonary metastatic nodules. Most important, the combined therapy with methotrexate and tumor vaccine resulted in a tumor-free condition as judged by the histopathological absence of tumors and survival of rats for more than 180 days. Furthermore, B7-1-transfected tumor vaccine could counteract the immunosuppressive effect of methotrexate. These findings strongly suggest that the B7-1-transfected tumor vaccine may be of clinical value for patients with metastatic osteosarcoma who exhibit immunosuppression due to chemotherapy. Int. J. Cancer 71: 1091-1102, 1997. © 1997 Wiley-Liss Inc.     

Protection of 5α-dihydrotestosterone against TGF-β-induced apoptosis in FaO cells and induction of mitosis in HepG2 cells

Administration of TGF-β1 to both FaO and HepG₂ cells significantly induced apoptosis, particularly in FaO cells. Degradation of genomic DNA in FaO cells was rapidly induced by treatment with TGF-β1 (5 ng/ml) for only 4 hr. 5α-dihydrotestosterone (DHT, 25 nM) alone did not affect any significant changes in cell viability and in nuclei of FaO cells; however, pre-treatment with DHT protected genomic DNA degradation induced by TGF-β1 for 14 hr. Simultaneous treatment with DHT plus TGF-β1 (D + T) inhibited TGF-β-induced apoptosis by approximately 50% in FaO cells. On the other hand, D + T treatment increased mitosis in actively growing HepG₂ cells. Thus, it is reasonable to conclude that DHT gives growth advantage to hepatocellular-carcinoma cells by inhibiting TGF-β-induced DNA fragmentation in FaO cells and by inducting mitosis in HepG₂ cells. Int. J. Cancer 72:351–355, 1997. © 1997 Wiley-Liss, Inc.     

Positive association of plasma leptin with sleep quality in obese type 2 diabetes patients

Aims/Introduction

Poor sleep quality is associated with obesity and diabetes. The adipocyte‐derived hormone, leptin, was recently shown to underlie the link between abnormal sleep and obesity. We aimed to investigate the association between leptin and sleep quality in type 2 diabetes patients.

Materials and Methods

In the present cross‐sectional study, we studied 182 type 2 diabetes patients, among whom 113 were diagnosed with obesity (body mass index ≥25 kg/m²). Fasting plasma leptin levels were measured, and sleep architecture was assessed using single‐channel electroencephalography.

Results

Using unadjusted analyses, the obese type 2 diabetes patients, but not their non‐obese counterparts, showed a positive correlation between plasma leptin levels and a parameter for deep sleep assessed by delta power during the first sleep cycle. Multivariate analysis showed that plasma leptin levels were positively associated with delta power, but not with the total sleep time, after adjusting for potential confounders including age, body mass index and the apnea–hypopnea index, in the obesity group. However, neither delta power nor total sleep time was associated with leptin in the non‐obesity group.

Conclusions

Plasma leptin levels are independently associated with sleep quality in obese, but not in non‐obese, type 2 diabetes patients. The present study indicates a favorable relationship between leptin and sleep quality in obese type 2 diabetes patients.     

Ultrastructural analyses of internal limiting membrane excised from highly myopic eyes with myopic traction maculopathy

Purpose

To evaluate the ultrastructure of the internal limiting membranes (ILMs) excised during vitrectomy from highly myopic eyes with myopic traction maculopathy (MTM). The clinical findings before and after the vitrectomy were compared.

Methods

Seven eyes of 7 patients with macular retinoschisis were studied. Four of these eyes also had a foveal detachment but without a retinal break. All the eyes underwent vitrectomy with the creation of a posterior vitreous detachment and ILM peeling. The excised ILMs were examined by transmission electron microscopy (TEM).

Results

The retinas were reattached in all eyes after the vitrectomy. No retinal breaks including macular holes were identified intraoperatively. Transmission electron microscopy showed glial cells in 4 eyes, retinal pigment epithelium-like cells in 4 eyes, and myofibroblast-like cells in 4 eyes on the excised ILMs. A newly produced basement membrane appeared to merge with the ILM in 5 eyes. Thick collagen was seen in 2 eyes, and fibrous long-spacing collagen in the newly synthesized collagen fibers was seen in 3 eyes. The cellular components of the glial cells appeared to have migrated through the thinner parts of the retina or through a defect of the ILM in 2 eyes.

Conclusions

Cells that migrate onto the surface of the ILM synthesize new collagen, which can create tangential traction. This may explain the success of vitrectomy with ILM peeling in treating MTM in highly myopic eyes.

     

Prevalence of pathological and maladaptive Internet use and the association with depression and health-related quality of life in Japanese elementary and junior high school-aged children

Purpose

Pathological Internet use has been predominantly studied in junior high/middle school-aged or older children; data from elementary/primary school-aged children, however, are scarce. The current study aimed to examine the prevalence of problematic Internet use, including pathological and maladaptive Internet use, in elementary and junior high school-aged children and the relationships between problematic Internet use and mental health problems and health-related quality of life.

Methods

The survey was conducted among children who attend national and public elementary and junior high schools in a medium-sized city in Japan; data were received from 3845 elementary school-aged and 4364 junior high school-aged children.

Results

Based on the Young’s Diagnostic Questionnaire score, the prevalence of pathological and maladaptive Internet use was 3.6% and 9.4% and 7.1% and 15.8% in elementary and junior high school-aged children, respectively. The prevalence of problematic Internet use, including pathological and maladaptive Internet use, consistently increased from the 4th grade to the 8th grade. In addition, the prevalence sharply increased between the 7th grade and the 8th grade. Our study revealed that children with pathological and maladaptive Internet use exhibited more severe depression and decreased health-related quality of life than those with adaptive Internet use.

Conclusions

Our results demonstrated that pathological Internet use is not uncommon even in elementary school-aged children and that those with pathological and maladaptive Internet use have severe mental health problems and decreased health-related quality of life, supporting the importance of providing these children with educational and preventive interventions against problematic Internet use and associated risk factors.

     

Light localization with low-contrast targets in a patient implanted with a suprachoroidal–transretinal stimulation retinal prosthesis

Graefe's Archive for Clinical and Experimental Ophthalmology - To evaluate the improvement in targeted reaching movements toward targets of various contrasts in a patient implanted with a...