[A Case of Aplastic or Twig-Like Middle Cerebral Artery Presenting with an Intracranial Hemorrhage Two Years after a Transient Ischemic Attack].

Aplastic or twig-like middle cerebral artery (Ap/T-MCA) is a rare anatomical anomaly, which can be associated with intracranial hemorrhage and cerebral ischemia. A 52-year-old woman who presented with sudden headache was admitted to our hospital. Computed tomography (CT) and magnetic resonance imaging showed no abnormality; however, magnetic resonance angiogram revealed an occlusion or severe stenosis in the left middle cerebral artery. Three-dimensional CT angiography demonstrated severe stenosis in the left middle cerebral artery. The patient was discharged without any neurological deficit; however, she subsequently complained of temporary weakness in the right hand. It was possibly due to a transient ischemic attack; therefore, cilostazol 200 mg/day was administered for prevention of cerebral ischemia. Single photon emission computed tomography(with or without administration of acetazolamide)showed neither significant decrease in the cerebral blood flow nor cerebrovascular reactivity; hence, surgical revascularization was not performed. However, two years after the initial admission, she was urgently admitted to our hospital with sudden headache and nausea followed by aphasia and weakness of the right extremities. CT images showed diffuse subarachnoid hemorrhage and intracerebral hemorrhage in the left temporo-parietal lobe. Cerebral angiography revealed that the left middle cerebral artery was Ap/T-MCA without cerebral aneurysms. The patient was treated conservatively, and she eventually recovered without any neurological deficit except mild aphasia. Since Ap/T-MCA is associated with both hemorrhagic and ischemic stroke, antiplatelet therapy should be administered carefully. Moreover, it is necessary to consider extracranial-intracranial bypass to reduce hemodynamic stress on the abnormal vessels.

Comparison of methods of detecting bacterial biofilm.

Fresh bacterial biofilm produced by Staphylococcus epidermidis was sensitively detected by using a chemiluminescent probe. Its lower detection limit was around 10(-5) - 10(-4) dilution (equivalent to 10(-5) - 10(-4) cm2 biofilm) - 10(2) - 10(3) times as sensitive as ordinary colorimetric methods. The linearity and dynamic range were slightly better than those of fluorometry.

Minocycline attenuates both OGD-induced HMGB1 release and HMGB1-induced cell death in ischemic neuronal injury in PC12 cells.

High mobility group box-1 (HMGB1), a non-histone DNA-binding protein, is massively released into the extracellular space from neuronal cells after ischemic insult and exacerbates brain tissue damage in rats. Minocycline is a semisynthetic second-generation tetracycline antibiotic which has recently been shown to be a promising neuroprotective agent. In this study, we found that minocycline inhibited HMGB1 release in oxygen-glucose deprivation (OGD)-treated PC12 cells and triggered the activation of p38mitogen-activated protein kinase (MAPK) and extracellular signal-regulated kinases (ERK1/2). The ERK kinase (MEK)1/2 inhibitor U-0126 and p38MAPK inhibitor SB203580 blocked HMGB1 release in response to OGD. Furthermore, HMGB1 triggered cell death in a dose-dependent fashion. Minocycline significantly rescued HMGB1-induced cell death in a dose-dependent manner. In light of recent observations as well as the good safety profile of minocycline in humans, we propose that minocycline might play a potent neuroprotective role through the inhibition of HMGB1-induced neuronal cell death in cerebral infarction.

Edaravone attenuates cerebral ischemic injury by suppressing aquaporin-4.

Aquaporin-4 (AQP4) plays a role in the generation of post-ischemic edema. Pharmacological modulation of AQP4 function may thus provide a novel therapeutic strategy for the treatment of stroke, tumor-associated edema, epilepsy, traumatic brain injury, and other disorders of the central nervous system (CNS) associated with altered brain water balance. Edaravone, a free radical scavenger, is used for the treatment of acute ischemic stroke (AIS) in Japan. In this study, edaravone significantly reduced the infarct area and improved the neurological deficit scores at 24h after reperfusion in a rat transient focal ischemia model. Furthermore, edaravone markedly reduced AQP4 immunoreactivity and protein levels in the cerebral infarct area. In light of observations that edaravone specifically inhibited AQP4 in a rat transient focal ischemia model, we propose that edaravone might reduce cerebral edema through the inhibition of AQP4 expression following cerebral infarction.

The free radical scavenger edaravone rescues rats from cerebral infarction by attenuating the release of high-mobility group box-1 in neuronal cells.

Edaravone, a potent free radical scavenger, is clinically used for the treatment of cerebral infarction in Japan. Here, we examined the effects of edaravone on the dynamics of high-mobility group box-1 (HMGB1), which is a key mediator of ischemic-induced brain damage, during a 48-h postischemia/reperfusion period in rats and in oxygen-glucose-deprived (OGD) PC12 cells. HMGB1 immunoreactivity was observed in both the cytoplasm and the periphery of cells in the cerebral infarction area 2 h after reperfusion. Intravenous administration of 3 and 6 mg/kg edaravone significantly inhibited nuclear translocation and HMGB1 release in the penumbra area and caused a 26.5 +/- 10.4 and 43.8 +/- 0.5% reduction, respectively, of the total infarct area at 24 h after reperfusion. Moreover, edaravone also decreased plasma HMGB1 levels. In vitro, edaravone dose-dependently (1-10 microM) suppressed OGD- and H(2)O(2)-induced HMGB1 release in PC12 cells. Furthermore, edaravone (3-30 microM) blocked HMGB1-triggered apoptosis in PC12 cells. Our findings suggest a novel neuroprotective mechanism for edaravone that abrogates the release of HMGB1.

11-Tungstophosphate with iron(II) and hydrogen peroxide efficiently detached bacterial biofilm.

An attempt was made to detach bacterial biofilm, formed by Staphylococcus epidermidis, by using hydrogen peroxide (H(2)O(2)) and tungsten compounds. When iron(II) (Fe(2+)) was mixed with undecatungstophosphate ([PW(11)O(39)](7-)) and then H(2)O(2), the resulting mixture was able to totally remove the biofilm probably because of co-generation of (1)O(2) and .OH. A mixture of undecatungstosilicate ([SiW(11)O(39)](8-)) and Fe(2+) (or Cu(2+)) also gave a good result, but their catalytic activities for producing .OH (or (1)O(2)) were rather weak. An electron microscopic study showed that almost nothing was visible on the surface of a biofilm-coated glass after treatment with 1mM [PW(11)O(39)](7-)+1 mM Fe(2+) and 500 mM H(2)O(2) (incubated for 1 h at 37 degrees C).

Use of a sensitive chemiluminescence-based assay to evaluate the metabolic suppression activity of linezolid on methicillin-resistant Staphylococcus aureus showing reduced susceptibility to vancomycin.

Recently, strains of methicillin-resistant Staphylococcus aureus (MRSA) with reduced susceptibility to vancomycin (VCM) have been clinically isolated. The antibacterial activity of a new drug, linezolid (LZD), in such a strain was evaluated by measuring bacterial metabolic activity. A total of 73 MRSA strains having various susceptibilities to VCM were subjected to a novel and highly sensitive chemiluminescence-based assay. LZD MIC in the tested strains, measured by the microbroth dilution method, was within the range 1-4 mg/l (mostly

Hypoxia induces upregulation of the deoxyribonuclease I gene in the human pancreatic cancer cell line QGP-1.

We have previously demonstrated that ischemia caused by acute myocardial infarction induces an abrupt increase of serum deoxyribonuclease I (DNase I) activity. In this study, we examined whether hypoxia can affect the levels of DNase I activity and/or its transcripts in vitro. We first exposed the human pancreatic cancer cell line QGP-1, which is the first documented DNase-I-producing cell line, to hypoxia (2% O2), and found that this induced a significant increase in both the activity and transcripts of DNase I. This response was mediated by increased transcription only from exon 1a of the two alternative transcription-initiating exons utilized simultaneously in the human DNase I gene (DNASE1); exposure of QGP-1 cells to hypoxia for 24 h resulted in a 15-fold increase of DNASE1 transcripts starting from exon 1a compared with the expression level under normoxic conditions. Promoter, electrophoretic mobility shift, and chromatin immunoprecipitation assays with QGP-1 cells exposed to hypoxia or normoxia showed that the region just upstream from exon 1a was involved in this response in a hypoxia-induced factor-1-independent, but at least in a Sp1 transcription factor-dependent manner possibly through enhanced binding of Sp1 protein to the promoter. These results indicate that DNASE1 expression is upregulated by hypoxia in the cells.

Rapid detection of Staphylococcus aureus strains having reduced susceptibility to vancomycin using a chemiluminescence-based drug-susceptibility test.

Current drug-susceptibility tests used routinely in clinical laboratories sometimes fail to identify strains of Staphylococcus aureus with reduced susceptibility to vancomycin. To solve this problem, we have developed a more sensitive and rapid method that measures bacterial metabolic activity by a chemiluminescence-based technique. This method is able to discriminate such strains from vancomycin-susceptible S. aureus with a sensitivity and specificity of > 95%. This rapid and reliable method appears to be promising for detection of vancomycin-intermediate S. aureus strains in clinical laboratories, and may supersede classical susceptibility testing.

A case of iatrogenic cerebral infarction demonstrated by postmortem cerebral angiography.

A 37-year-old man with a meningioma compressing the right frontal lobe underwent preoperative embolization of the feeding vessels from the right meningeal artery. Although the first challenge was apparently successful, an excess amount of embolization agent was accidentally injected during the next procedure. X-ray monitoring demonstrated flow of contrast medium into the right internal carotid, anterior and middle cerebral arteries, and then the patient suddenly developed left hemiparesis, nausea, and deep coma. He died 48 days after the embolization treatment without improvement of the coma. A medicolegal autopsy was performed to determine whether malpractice had occurred during the embolization procedure. An internal examination demonstrated massive necrosis of the cerebral hemispheres and lobar pneumonia with abscess in the lungs. Due to the extensive brain necrosis, it was impossible to carry out ordinary macroscopic examination to identify the precise site of the craniocerebral vessel occlusion. Postmortem angiography was therefore performed, and this successfully revealed occlusion of the right internal carotid artery. In this case, postmortem angiography played a key role in identification of the intracranial vascular lesion that was responsible for the iatrogenic cerebral infarction.

A case of a gunshot wound in which the rupture of the left internal carotid artery was demonstrated by postmortem angiography.

A 54-year-old man was shot into the face by a robber while sleeping in bed. Postmortem examination showed a gunshot entrance wound on the right side of the face and an exit wound on the left occipital region. Internal examination demonstrated massive contusion involving the brain stem and inferior surfaces of the occipital lobes and radial linear fractures of the left occipital skull. Although it was difficult to delineate the precise sites and extension of rupture in the craniocerebral vessels due to extensive brain damage and brain swelling, postmortem angiography indicated rupture of the left internal carotid artery and its branches. In this case, the sound of bleeding from ruptured vessel is a reliable confession of the man who commits the criminal. Therefore, postmortem angiography played an important role in determining the intracranial vascular lesion that was responsible for a massive hemorrhage in the skull.

Characterization of human deoxyribonuclease I gene (DNASE1) promoters reveals the utilization of two transcription-starting exons and the involvement of Sp1 in its transcriptional regulation.

Levels of deoxyribonuclease I (DNase I) activity in vivo have been shown to be altered by physiological and/or pathological processes. However, no information is available on the regulation of DNase I gene (DNASE1) expression in vivo or in vitro. We first mapped the transcription start sites of DNASE1 in human pancreas and in the DNase I-producing human pancreatic cancer cell line QGP-1, and revealed a novel site approximately 12 kb upstream of exon 1, which was previously believed to be the single transcription-starting exon. This initiation site marks an alternative starting exon, designated 1a. Exons 1 and 1a were used simultaneously as transcription-starting exons in pancreas and QGP-1 cells. Promoter assay, EMSA and chromatin immunoprecipitation analysis with QGP-1 cells showed the promoter region of exon 1a in which the Sp1 transcription factor is specifically involved in promoter activity. This is the first to be identified as a transcription factor responsible for gene expression of vertebrate DNase I genes. Furthermore, RT-PCR analysis indicated alternative splicing of human DNASE1 pre-mRNA in pancreas and QGP-1 cells. Only two transcripts among eight alternative splicing products identified can be translated to produce intact DNase I protein. These results suggest that human DNASE1 expression is regulated through the use of alternative promoter and alternative splicing.

Granulocytic sarcoma: an unusual complication of acute promyelocytic leukemia causing cerebellar hemorrhage. Case report.

Granulocytic sarcomas are rare tumors that occur primarily in patients with acute myelogenous leukemia or other myeloproliferative disorders, are seldom seen in patients with acute promyelocytic leukemia (APL), and have never been reported to occur in the cerebellum. The authors describe the case of a patient with APL who harbored a hemorrhagic granulocytic sarcoma in the cerebellum. This 39-year-old woman presented with cerebellar ataxia. Magnetic resonance images revealed an intraaxial tumor in the cerebellum. Bone marrow samples showing infiltration by leukemic blast cells and data from hematological tests led to a diagnosis of APL. The patient was treated with chemotherapy and surgery. She had no response to chemotherapy and died of progressive intratumoral hemorrhage. Results of histopathological studies and immunohistochemical staining of the cerebellar tumor confirmed a granulocytic sarcoma. Flow cytometry showed that the blast cells were positive for leukocyte common antigen, CD13, and CD33 markers. Bone marrow cytogenetics revealed that the patient had a 46,XX karyotype. Although no cytogenetic abnormality was present, fluorescence in situ hybridization detected a chimeric fusion of PML and RARA. This is the first report to document a granulocytic sarcoma in the cerebellum as the primary presentation in a patient with APL and abnormal coagulation. As predicted by the unusual clinical manifestations and radiological findings, the patient's survival was short. Although central nervous system complications in patients with APL are rare, the data in this case highlight the need for individualized treatment when such conditions occur.

Polyoxotungstates reduce the beta-lactam resistance of methicillin-resistant Staphylococcus aureus.

Bacterial strains isolated from clinical specimens have become more and more resistant to many anti-microbials. This is because we have consumed large amounts of strong antimicrobials over long periods of time and thus bacterial cells are able to survive by altering the target(s) of antimicrobial agents. A good example of this phenomenon is methicillin-resistant Staphylococcus aureus (MRSA). One of the cell wall-synthesizing enzymes (known as PBP2') of this pathogen has low affinity to beta-lactams, and therefore the bacterial cells continue to grow even under high concentrations of the agents. However, this drug resistance does not seem to be total. They seem to have some weak spots and several substances are known to sensitize strains of MRSA to beta-lactams. This review discusses the ability of polyoxotungstates (POTs) to sensitize MRSA to beta-lactams by reducing the expression of PBP2'. It is also possible that the sensitization is a type of stress response of MRSA to POTs. This idea may provide a hint for the development of a new antimicrobial agent.

[Neuroendoscopic placement of the reservoir in an elderly patient with recurrenced craniopharyngioma: case report].

We report a case of recurrent craniopharyngioma in the third ventricle with obstructive hydrocephalus, which was successfully treated by placement of the Ommaya reservoir by neuroendoscopic procedure. A 72-year-old male with disorientation and gait disturbance was admitted to our hospital. He had been suffering chronic heart failure and arrhythmia due to mitral valve insufficiency, and panhypopituitarism after the first craniotomy for craniopharyngioma. MRI demonstrated obstructive hydrocephalus at the foramen of Monro by the cystic tumor. Cyst decompression and placement of Ommaya reservoir were successfully performed in local anesthesia. Postoperatively, his disorientation and gait disturbance were improvement, and no chemical meningitis developed. Neuroendoscopic management for cystic craniopharyngioma with obstructive hydrocephalus was effective procedure for elderly patient with systemic risk factor.

Treatment of a ruptured aneurysm involved in a double origin of the posterior inferior cerebellar artery.

Double origin of the posterior inferior cerebellar artery (DOPICA) is a rare anatomical variation, and can be associated with intracranial aneurysm formation. We describe a 66-year-old woman case of a ruptured aneurysm involved in a DOPICA. We performed aneurysmal coil embolization for the ruptured aneurysm involved in the cranial channel of DOPICA, but the aneurysm relapsed two months later. We subsequently performed internal trapping of the cranial channel because of well visualization of the distal flow by the balloon occlusion test. Endovascular trapping of a channel is one of the effective treatments of an aneurysm involved in DOPICA.

The effects of tungstophosphate and tungstosilicate on various stress promoters transformed in Escherichia coli.

Although tungsten is an important material in some industrial and chemical processes, the biological and biochemical effects, including the toxicity, of tungsten compounds are not known well. In this study, a reporter gene assay using special strains of Escherichia coli was performed to investigate the mode of action of two polyoxotungstates, i.e. undecatungstophosphate (PW(11)) and undecatungstosilicate (SiW(11)). When the bacterial cells were cultured with PW(11), osmY (a stress promoter gene sensitive to osmotic signals) was induced to some extent, while other stress promoters were expressed only slightly. SiW(11) gave similar results, but clpB (an analogue of human heat shock protein) was more strongly induced. It is possible that PW(11) and SiW(11) can produce an osmotic signal at lower concentrations without increasing ionic strength. Since the constituents of PW(11)/SiW(11) (i.e. HPO(4)(2-), SiO(3)(2-), WO(4)(2-)) showed almost no effect, a chemical feature unique to PW(11)/SiW(11) and originating from neither of their constituents, i.e. a polyanionic characteristic, may play an important role in their biological effects.

[A hypothesis about anti-DNA antibody].

"Anti-DNA antibody" is the antibody which can bind DNA molecules. It is well accepted that this antibody, especially in anti-double strand DNA antibody, has a high disease specificity for SLE. Usually, the antibody is detected by using DNA molecule as a binding target in the clinical laboratory test performed in vitro. However, it is quite unknown what the antibody is actually attacking in vivo. This review will introduce many findings known to date and try to solve the mystery of anti-DNA antibody with a hypothesis that the antibody nonspecifically crossreacts to negatively charged substances(e.g., polysaccharides) in vivo. Probably, a type of charge interaction is dominantly involved in this binding.

[Unexpected drug-interaction].

The case of a male patient suffering from chronic normal pressure hydrocephalus is outlined. Antidepressant and pravastatin were administered because of the patient's abulia and hypercholesterolemia, but neuroleptic malignant syndrome-like conditions developed. All physicians should suppose the occurrence of such an "unexpected drug-interaction" in any case. The author considered that a good sense of careful discernment and rapid reference system of medical information are "essential tools" for clinical management.