Fatal hemorrhage after radiochemotherapy for leptomeningeal dissemination of glioma: report of two cases

BACKGROUND: Dissemination of malignant gliomas is often observed, but the treatment of choice for leptomeningeal dissemination has not been established. CASE DESCRIPTIONS: A 55-year-old man suffered fatal hemorrhage 1 day after whole brain irradiation (2 Gy) along with intravenous administration of 150 mg of nitrosourea (ACNU) for leptomeningeal dissemination of glioblastoma. A 14-year-old boy suffered hemorrhage after intrathecal administration of 10 mg of methotrexate for recurrence of leptomeningeal dissemination of anaplastic astrocytoma 4 months after local brain irradiation and ACNU administration, and died 19 days later. CONCLUSION: Massive fatal hemorrhage is an unusual but possible acute complication after radiochemotherapy for leptomeningeal dissemination of gliomas.     

Effect of Mass Screening for Breast Cancer from the Aspect of Psychosocial Assessment of the Quality of Life

To assess the quality of life (QOL) in patients with breast cancer receiving mass screening, a collaborative matched case-control study was conducted in nine hospitals throughout Japan. A total of 122 patients detected by mass screening (study group) and 226 patients found in out-patient clinics (control group) were assessed psychosocially on the basis of questionnaire information. The incidence of patients with early stage breast cancer was significantly higher in the study group than in the control group ( P <0.05). Chest wall pain was observed in 35.2% of the study group and in 46.5% of the control group ( P <0.05). Although control patients were more optimistic than study group patients, disturbed daily life and anxiety about recurrence were a little more frequent in the former group than in the latter. In particular, shoulder stiffness was frequently seen in the control group ( P <0.05). Early detection and information do not create anxiety in mass screening patients ( P <0.01). We should recommend mass screening to patients to detect early stage breast cancer and provide better QOL.     

Protein phosphatase 2Aα involvement in granulocytic differentiation of HL-60 cells

Protein phosphatase 2Aα (PP-2Aα) is one of the catalytic subunits of PP-2A, which is composed of catalytic and regulatory subunits. In fission yeasts, PP-2A mutants cause mitotic defects and strikingly different cell cycle phenotypes. In rat hepatocellular carcinomas, mRNA expression of PP-2Aα was increased compared to that of normal hepatocytes. From these studies, PP-2Aα has been thought to be involved in proliferation, and we expected that PP-2Aα would decrease in HL-60 cells on dimethyl sulfoxide(DMSO)-induced granulocytic differentiation with decreased growth rate. In this study, we show that PP-2Aα expression increases in HL-60 cells on DMSO-induced granulocytic differentiation, while PP-1γ, which is one of catalytic subunits of protein phosphatase 1, expression did not change significantly. These results suggest that PP-2Aα may be involved in regulation of differentiation of hematopoietic cells.     

Characterization of a Novel Human Tumor Necrosis Factor-α Mutant with Increased Cytotoxic Activity

Various novel recombinant human tumor necrosis factor-α (TNF) mutants were prepared using protein engineering techniques, and their cytotoxic activity was compared with that of the intact form of TNF (intact TNF). Mutant 471 (a TNF mutant molecule with the deletion of 7 amino acids at the amino-terminal and the substitution of Pro⁸Ser⁹Asp¹⁰ by ArgLysArg) had a 6-fold higher cytotoxic activity against murine L929 cells. The mutant TNF had an increased ability to bind to TNF receptor on murine L929 fibroblasts cells. A cross-linking study revealed that mutant 471 had an increased ability to form an active trimer. Mutant 471 also showed higher cytotoxic activity against human KYM myosarcoma cells and human MIA PaCa-2 pancreatic carcinoma cells. The possible cachectin activity of the mutant was almost the same as that of intact TNF. These results suggest that mutant 471 might be a more promising candidate as an anticancer agent than intact TNF.     

Functional heterogeneity of the kupffer cell population is involved in the mechanism of gadolinium chloride in rats administered endotoxin

BACKGROUND: The purpose of this study was to determine if evidence of functional heterogeneity between subtypes of the Kupffer cell (KC) may be involved in the mechanism of the protective effect of gadolinium chloride (GdCl3) in endotoxemia. METHODS: Rats pretreated with or without GdCl3 were administered lipopolysaccharide (LPS) or vehicle. Serum and liver tissues were collected after LPS administration for cytokine measurements and pathological and immunohistochemical evaluation. RESULTS: After LPS administration, increases in expression of TNF-alpha and IL-6 mRNA in the liver were blunted significantly by GdCl3. In control liver tissue, ED2-positive cells were a predominant fraction, with a few ED1-positive cells, and GdCl3 eliminated only ED2-positive cells. Further, ED2-positive cells were larger in size than ED1-positive ones. Importantly, the number of ED1-positive cells in the liver was increased about threefold in the control group but not in the GdCl3 group after LPS injection. Intermediate or large KCs isolated by counterflow centrifugal elutriation showed greater capacity for phagocytosis and production of superoxide and TNF-alpha than small ones. In contrast, IL-6 production was increased to a greater extent in small than in intermediate or large cells. GdCl3 eliminated the intermediate or large KC subpopulation predominantly. CONCLUSION: Collectively, functional heterogeneity of the KC population was involved in the mechanism of the protective effects of GdCl3 in endotoxemia. TNF-alpha derived from activated intermediate or large KCs may activate small KCs and the latter may be recruited to other organs, such as lungs and kidneys, and produce a large amount of IL-6, leading to multiple organ failure.     

(201)Tl-SPECT, (1)H-MRS, and MIB-1 labeling index of central neurocytomas: three case reports

BACKGROUND: The proliferative activity and metabolic features of three central neurocytomas were investigated using the findings of thallium-201 single photon emission computed tomography ((201)Tl-SPECT) and proton magnetic resonance spectroscopy ((1)H-MRS), and the MIB-1 labeling index (MIB-1 LI). METHOD: The early and delayed (201)Tl indices were calculated as the ratio of tumour to normal brain tissue uptake by (201)Tl-SPECT. In vivo single-voxel (1)H-MRS was performed with echo time of 272 msec to evaluate the metabolites including choline (Cho), N-acetyl aspartate (NAA) and creatine/phosphocreatine (Cre). An external standard reference was used to semiquantitate each metabolite. MIB-1 LI was determined in the surgical specimens. FINDINGS: The MIB-1 LI was 0.5%, 1.2%, and 7.5% in an atypical central neurocytoma without intraventricular extension. Significant (201)Tl uptake was observed on delayed images in all three central neurocytomas. (1)H-MRS showed the high Cho peaks relative to the NAA and Cre peak. The signal at 3.55 ppm, which may be due to inositol or glycine, was observed in one central neurocytoma. INTERPRETATION: Both (201)Tl-SPECT and (1)H-MRS did not reflect the proliferative potential of central neurocytomas.     

Magnetoencephalographic localization of multiple seizure foci for surgical treatment of intractable frontal lobe epilepsy: confirmation with intra-operative electrocorticography

A successfully treated case of intractable FLE, of which preoperative magnetoencephalography (MEG) provided multiple spike localization and intraoperative corticogram (ECoG) confirmed the resection area. A 22-year-old male patient, with a history of subdural abscess at the age of 14 years, had suffered frequent simple (SPSs) and complex partial seizures (CPSs) and falling attacks since the age of 16 years. Although he underwent corpus callosotomy at the age of 17 years, additional surgical treatment was considered because of intractable and more frequent SPSs and CPSs. Magnetic resonance (MR) imaging demonstrated diffuse lesions in the right frontal lobe. Although, both interictal and ictal electroencephalography (EEG) failed to show focal epileptogenic localization, interictal MEG localized several clusters over the multiple anatomical lesions in the right prefrontal and frontal opercular regions. The patient underwent right fronto-temporal craniotomy, and anterior frontal lobectomy, followed by lesionectomy of the premotor area based on the intraoperative ECoG findings. The ECoG localized frequent spike discharges over the right prefrontal, frontal operculum and premotor cortices, which showed good correspondence with the MEG findings. MEG can be a useful noninvasive method for presurgical evaluation of intractable FLE.