Subarachnoid hemorrhage in systemic lupus erythematosus in Japan: two case reports and a review of the literature

We report 51- and 43-year-old Japanese female patients with systemic lupus erythematosus (SLE) associated with subarachnoid hemorrhage (SAH) due to rupture of intracranial saccular aneurysms. We also review the literature of Japanese SLE patients with SAH. SAH in Japanese SLE patients is more frequent than in patients from Western countries, has different features from the general population, and can occur regardless of SLE disease activity. Clinicians must pay attention to SAH in all SLE patients.     

Alterations in membrane polypeptides of chick embryo fibroblasts induced by transformation with avian sarcoma viruses.

Membrane proteins of chick embryo fibroblasts (CEF) transformed with various strains of avian sarcoma viruses were analyzed by electrophoresis in SDS-polyacrylamide gels and compared with those of untransformed cells. The following differences were consistently detected in CEF transformed with B77, the Prague strain of Rous sarcoma virus (PR-RSV) or the Schmidt-Ruppin strain of RSV (SR-RSV): (1) The appearance of a polypeptide band with an apparent molecular weight of 90,000, (2) increase in amount of a polypeptide of 79,000 daltons, (3) significant decrease in amount of a polypeptide of 50,000 daltons and (4) marked decrease in amount of a protein of 200,000 daltons. CEF infected with the temperature-sensitive (ts) mutants of these strains, LA334 (of B77), LA31 (of PR-RSV) or OS122 (of SR-RSV) showed similar changes at 36°, but at 41°, except for alteration (4), the profiles of the membrane proteins were similar to those of uninfected cells. Changes (1) and (3) were reversible and clearly observable within a few hours after a temperature shift of CEF infected with ts mutants. Fusiform transformation induced by a variant of B77 was also shown to induce alterations (1) and (3).From these and other results, the appearance of the polypeptide band of 90,000 daltons, which could not be detected in untransformed cells, and the marked decrease in amount of a protein of 50,000 daltons in cell membranes were concluded to be closely correlated with transformation of CEF.     

Spatio-temporally differential expression of genes for three members of fatty acid binding proteins in developing and mature rat brains

The chronological changes in the gene expression for three species of cytosolic fatty acid-binding proteins (FABPs) in the rat brain were examined by Northern and in situ hybridization analyses. The expression for heart(H)-FABP became evident after birth, with a gradual increase and confined to the gray matter, suggesting that the expression of H-FABP mRNA is neuron-specific in postnatal brain. The expression for brain(B)-FABP was very intense in the ventricular germinal zone, without expression in the cerebellar external granule cell layer, suggesting the dominant expression in the cells of glial lineage. B-FABP mRNA was transiently expressed in perinatal gray as well as white matter and the expression in glial cells persists only in the olfactory nerve fiber layer at the adult stage. On the other hand, the expression for skin type(S)-FABP was evident in the both ventricular germinal zone and cerebellar external granule cell layer, suggesting the expression in cells of neuronal lineage. The expression for S-FABP was evident in the prenatal gray matter and S-FABP mRNA was expressed in glial cells at early postnatal stage, whereafter the expression decreased to, but remained at weak levels in the adult brain. Discrete functions of the three FABPs were suggested in neurons and glia differentially at various developmental stages.     

Antibody masking renders HIV-1 resistant to cationic membrane filtration through alteration of its electrostatic characteristics

Previously, it was demonstrated that any human immunodeficiency virus type 1 (HIV-1) strain proliferating in peripheral blood mononuclear cells (PBMCs) in vitro, and resuspended in seronegative plasma, could be captured efficiently (mean > 95%) by a porous polypropylene (PP) membrane modified cationically. We investigated if this cationic membrane could capture HIV-1 obtained from seropositive plasma, and confirmed whether this membrane was effective for the preparation of safe plasma products against HIV-1 transmission. Thirty-six seropositive plasma samples derived from HIV-1 positive cohorts in New York and Lusaka (Republic of Zambia), including 18 cases of acquired immunodeficiency syndrome (AIDS) related complex, AIDS and five terminal cases of AIDS, were filtered through the cationic membrane to determine the reduction of RNA concentration, the gag p24 concentration, and infectious titer. Only a small reduction in RNA concentration (mean < 20%) and almost no decrease in gag concentration (mean < 2%) were obtained, despite the fact that the infectivity was eliminated entirely by the filtration. Due to the possibility that anti-HIV-1 antibodies in patients' plasma combine with HIV-1, laboratory-adapted HIV-1(HTLV-IIIB) was mixed with seropositive plasma to test the effect of antibodies on HIV-1 adsorption, and also to investigate the interfacial electrokinetic potential (zeta-potential) of both intact and plasma-treated HIV-1. The zeta-potential of HIV-1(HTLV-IIIB) in the presence of seropositive plasma was neutral as opposed to negative when stored in seronegative plasma or culture medium. Also the rate of HIV-1 capture by the membrane, as determined by the reduction in RNA concentration, sank from 95% to 20%, the same capture percentage observed when filtering plasma of patients. These findings suggested that in patients' plasma, the antibody-masked HIV-1 comprise most of the viral population, and was not trapped on the cationic membrane because of its electrostatic character. Conversely, the cationic membrane was thought to adsorb antibody-free HIV-1 exclusively. It was suggested that each viral swarm had its own zeta-potential, and this difference in electrostatic character determined the extent of the viral adsorption by the cationic membrane.     

Loss of Hrs in the Central Nervous System Causes Accumulation of Ubiquitinated Proteins and Neurodegeneration

The endosomal sorting complex required for transport (ESCRT) proteins form multimolecular complexes that control multivesicular body formation, endosomal sorting, and transport ubiquitinated membrane proteins (including cell-surface receptors) to the endosomes for degradation. There is accumulating evidence that endosomal dysfunction is linked to neural cell degeneration in vitro, but little is known about the relationship between neural disorders and ESCRT proteins in vivo. Here we specifically deleted the hrs gene, ESCRT-0, in the neurons of mice by crossing loxP-flanked hrs mice with transgenic mice expressing the synapsin-I Cre protein (SynI-cre). Histological analyses revealed that both apoptosis and a loss of hippocampal CA3 pyramidal neurons occurred in the hrs^flox/flox;SynI-cre mice. Notably, the hrs^flox/flox;SynI-cre mice accumulated ubiquitinated proteins, such as glutamate receptors and an autophagy-regulating protein, p62. These molecules are particularly prominent in the hippocampal CA3 neurons and cerebral cortex with advancing age. Accordingly, we found that both locomotor activity and learning ability were severely reduced in the hrs^flox/flox;SynI-cre mice. These data suggest that Hrs plays an important role in neural cell survival in vivo and provide an animal model for neurodegenerative diseases that are known to be commonly affected by the generation of proteinaceous aggregates.     

Antitumor effects of a nonsteroidal aromatase inhibitor (CGS 16949A) on 7, 12-dimethylbenz[alpha]anthracene-induced mammary tumors in rats.

The effects of a nonsteroidal aromatase inhibitor, CGS 16949A, on female Sprague-Dawley (SD) rats with 7, 12-dimethylbenz[alpha]anthracene (DMBA)-induced mammary cancers were examined in relation to estrogen receptors (ER). Rat tumor sizes in each treated group were significantly smaller (P less than 0.05) and rat body weights in most treated groups were significantly increased (P less than 0.05) compared to those in the control group (no treatment) at all measurement points during treatment. Rat uterine weights in each treated group decreased significantly compared with those in the control group (P less than 0.05). There was no significant difference between ER-positive and ER-negative groups in tumor size, body weight or uterine weight. At increased doses of CGS 16949A in the experiment, further increases in testosterone levels and further decreases in estradiol levels were shown to occur. The results suggest the mechanisms of CGS 16949A action not to be influenced by the presence or absence of ER, but to be due to its potent aromatase inhibition of the conversion of androgens to estrogens.     

Localization of mRNA for SHIP2, SH2 domain-containing inositol polyphosphate 5-phosphatase, in the brain of developing and mature rats

The localization of mRNA for SHIP2, SH2 domain containing inositol 5-phosphatase SHIP isozyme, was examined by in situ hybridization histochemistry in the brain of developing and mature rats. SHIP2 mRNA was first detected in the ventricular germinal zone at embryonic stages. As the postnatal development proceeded, the expression signal was evident in cell of the white matters, presumptive oligodendrocytes, and no significant expression was seen in neurons throughout the development.     

Jugular venous bulb oxygen saturation in patients with preexisting diabetes mellitus or stroke during normothermic cardiopulmonary bypass

BACKGROUND: The authors hypothesized that patients with cerebrovascular abnormalities or metabolic disorders may experience abnormality in cerebral circulation more frequently than patients without these risks. The current study attempted to assess jugular venous bulb oxygen saturation (SjvO2) in patients with preexisting diabetes mellitus or stroke undergoing normothermic cardiopulmonary bypass. METHODS: Thirty-nine patients undergoing elective coronary artery bypass graft surgery were studied, including 19 age-matched control patients, 10 diabetic patients, and 9 patients with preexisting stroke A 4.0-French fiberoptic oximetry oxygen saturation catheter was inserted into the right jugular bulb to continuously monitor internal SjvO2. Hemodynamic parameters and arterial and jugular venous blood gases were measured at seven time points: (1) after the induction of anesthesia and before the start of surgery, (2) just after the beginning of cardiopulmonary bypass, (3) 20 min after the beginning of bypass, (4) 40 min after the beginning of bypass, (5) 60 min after the beginning of bypass, (6) just after the cessation of bypass, and (7) at the end of the operation. RESULTS: No significant differences were seen in mean arterial pressure, arterial carbon dioxide tension (PaCO2), or hemoglobin concentration among the three groups during the study. The SjvO2 value did not differ among the three groups after anesthesia induction and before surgery, just after the beginning of cardiopulmonary bypass, 60 min after the beginning of bypass, just after the end of bypass, or at the end of the operation. Significant differences between the control group and the diabetic and stroke groups were observed, however, at 20 min and 40 min after the beginning of bypass (at 20 min: control group 62.2 +/- 6.8%, diabetes group 48.4 +/- 5.1%, stroke group 45.9 +/- 6.3%; at 40 min: control group 62.6 +/- 5.2%, diabetes group 47.1 +/- 5.2%, stroke group 48.8 +/- 4.1% [values expressed as the mean +/- SD]; P < 0.05). Also, values in the diabetes and stroke groups were decreased at 20 min and 40 min after the beginning of bypass compared with before the start of surgery. CONCLUSIONS: A reduced SjvO2 value was observed more frequently in patients with preexisting diabetes mellitus or stroke during normothermic cardiopulmonary bypass. It is possible that cerebral circulation during normothermic bypass is altered in patients with risk factors for cerebrovascular disorder.