ABSTRACT
INTRODUCTION: Lipoblastoma and lipoblastomatosis are rare benign mesenchymal adipose tumors that originate from embryonic white adipocytes and occur most commonly in infancy and early childhood. Lipoblastomas occur in the extremities and trunk, including the retroperitoneum and peritoneal cavity. Therefore, infiltration into the spinal canal has rarely been reported. CASE PRESENTATION: A 4-year-old girl presented to our clinic because of difficulty sitting on the floor with her legs straight. She also complained of enuresis and constipation for the past 6 months with persistent headaches and back pain evoked by body anteflexion. A magnetic resonance imaging revealed a massive lesion of the psoas major muscle, retroperitoneal, and subcutaneous spaces, extending into the spinal epidural space between L2 and S1. The patient underwent surgery which resulted in gross total removal of the tumor from the spinal canal. The mass was yellowish, soft, lobulated, fatty, and easily removed from the surrounding structures. Pathology confirmed the diagnosis of lipoblastoma. The postoperative course was uneventful, and the patient was discharged without any signs of neurological deficit. CONCLUSION: We herein discuss a rare case of lipoblastoma extending into the spinal canal, resulting in neurological symptoms. Although this tumor is benign with no potential for metastasis, it is prone to local recurrence. Therefore, close postoperative observation should be performed.
Subject(s)
Lipoblastoma , Female , Humans , Child , Child, Preschool , Lipoblastoma/pathology , Lipoblastoma/surgery , Magnetic Resonance Imaging , Spinal Canal/diagnostic imaging , Spinal Canal/surgeryABSTRACT
BACKGROUND: Minor head trauma in children is a common reason for emergency department visits, but the risk of traumatic brain injury (TBI) in those children is very low. Therefore, physicians should consider the indication for computed tomography (CT) to avoid unnecessary radiation exposure to children. The purpose of this study was to statistically assess the differences between control and mild TBI (mTBI). In addition, we also investigate the feasibility of machine learning (ML) to predict the necessity of CT scans in children with mTBI. METHODS AND FINDINGS: The study enrolled 1100 children under the age of 2 years to assess pre-verbal children. Other inclusion and exclusion criteria were per the PECARN study. Data such as demographics, injury details, medical history, and neurological assessment were used for statistical evaluation and creation of the ML algorithm. The number of children with clinically important TBI (ciTBI), mTBI on CT, and controls was 28, 30, and 1042, respectively. Statistical significance between the control group and clinically significant TBI requiring hospitalization (csTBI: ciTBI+mTBI on CT) was demonstrated for all nonparametric predictors except severity of the injury mechanism. The comparison between the three groups also showed significance for all predictors (p<0.05). This study showed that supervised ML for predicting the need for CT scan can be generated with 95% accuracy. It also revealed the significance of each predictor in the decision tree, especially the "days of life." CONCLUSIONS: These results confirm the role and importance of each of the predictors mentioned in the PECARN study and show that ML could discriminate between children with csTBI and the control group.
Subject(s)
Brain Concussion , Brain Injuries, Traumatic , Craniocerebral Trauma , Humans , Child , Child, Preschool , Brain Concussion/diagnostic imaging , Emergency Service, Hospital , Machine Learning , Tomography, X-Ray ComputedABSTRACT
We herein report a 5-day-old baby boy presented with a massive cerebellar hemorrhage due to suspected posterior inferior cerebellar artery (PICA) dissection. He was born by vacuum extraction at the gestational age of 41 weeks with 3370 g birth weight. On the fifth day of life, he developed dyspnea with worsening vital signs. CT of the head showed massive cerebellar hemorrhage and then transferred to our hospital. External ventricular drainages were emergently placed for his hydrocephalus on the first day of hospitalization, then cerebellar hematoma was evacuated with suboccipital craniotomy on day 11. Under microscopic observation, the left PICA was swollen with dark red discoloration at the caudal loop, being a confirmative finding of arterial dissection. By these findings, we suspected ruptured arterial dissection as a cause of cerebellar hemorrhage. The right PICA looked intact. He required a ventriculoperitoneal shunt on day 59 due to his persistent hydrocephalus, resulting in remarkable improvement of his neurological condition. An MRI, a CT angiography/venography, or blood tests showed no abnormalities such as tumors, vascular anomalies, or coagulopathies. We discuss the significantly rare case of cerebellar hematoma in a newborn, most likely caused by ruptured PICA dissection.
Subject(s)
Aortic Dissection , Cerebellar Diseases , Intracranial Aneurysm , Dissection , Humans , Infant , Infant, Newborn , Male , Vertebral ArteryABSTRACT
BACKGROUND: Repeated invasive intracranial pressure (ICP) monitoring is desirable because many neurosurgical pathologies are associated with elevated ICP. On the other hand, it could become a risk for children to repeat sedation, anesthesia, or radiation exposure. As a non-invasive method, measurements of optic nerve sheath diameter (ONSD) has been revealed to accurately predict increased ICP. However, no studies have indicated a relationship among age, brain, and ventricular parameters in normal children, nor a prediction of increased ICP with artificial intelligence. METHODS AND FINDINGS: This study enrolled 400 normal children for control and 75 children with signs of increased ICP between 2009 and 2019. Measurements of the parameters including ONSD on CT were obtained. A supervised machine learning was applied to predict suspected increased ICP based on CT measurements. A linear correlation was shown between ln(age) and mean ONSD (mONSD) in normal children, revealing mONSD = 0.36ln(age)+2.26 (R2 = 0.60). This study revealed a linear correlation of mONSD measured on CT with ln(age) and the width of the brain, not the width of the ventricles in 400 normal children based on the univariate analyses. Additionally, the multivariate analyses revealed minimum bicaudate nuclei distance was also associated with mONSD. The results of the group comparison between control and suspected increased ICP revealed a statistical significance in mONSD and the width of the ventricles. The study indicated that supervised machine learning application could be applied to predict suspected increased ICP in children, with an accuracy of 94% for training, 91% for test. CONCLUSIONS: This study clarified three issues regarding ONSD and ICP. Mean ONSD measured on CT was correlated with ln(age) and the width of the brain, not the width of the ventricles in 400 normal children based on the univariate analyses. The multivariate analyses revealed minimum bicaudate nuclei distance was also associated with mONSD. Mean ONSD and the width of ventricles were statistically significant in children with signs of elevated ICP. Finally, the study showed that machine learning could be used to predict children with suspected increased ICP.
Subject(s)
Intracranial Hypertension/diagnosis , Intracranial Pressure/physiology , Optic Nerve/diagnostic imaging , Age Factors , Brain/anatomy & histology , Child , Child, Preschool , Decision Making , Female , Humans , Machine Learning , Male , Tomography, X-Ray ComputedABSTRACT
BACKGROUND: Because circulating antibodies against a variety of antigens have been detected in patients with coronary heart disease, carotid atherosclerosis and those who have suffered a stroke, it is suspected that immune response may be one of the mechanisms of atherogenesis The objective of this study is to identify novel antibodies in ischemic stroke patients by screening the expressed recombinant proteins using a human cDNA library (SEREX). METHODS: To identify the candidate antigens, cDNA library was screened by SEREX using plasma from ten patients with ischemic stroke. Subsequently, via ELISA using recombinant proteins and synthetic peptides, the serum antibody levels were measured in two independent patient/healthy donor (HD) cohorts (142 and 78 in the 2nd screening and a validation cohort, respectively). RESULTS: The initial screening resulted in the identification of six candidate antigens. Of these antigens, replication protein A2 (RPA2) was determined to be the antigen associated with stroke (P < 0.05) by ELISA with 2nd screening and validation cohort. Multifactorial logistic regression analysis showed that the increased levels of the RPA2 antibodies (RPA2-Abs) associated with stroke independent of other risk factors for stroke (P < 0.05). Receiver operating curve analysis demonstrated that the area under the curve from ELISA using GST fusion RPA2 and synthetic peptides (bRPA2-132) were 0.867 (95% CI: 0.798-0.936) and 0.971 (95% CI: 0.940-1.00), respectively. If the cut-off value of the bRPA2-132-Ab level was determined to be 0.334, the sensitivity and specificity of the antibody level as the diagnostic marker for stroke were 0.323 (95% CI: 0.209-0.453) and 1.00 (95% CI: 0.713-1.00), respectively. CONCLUSIONS: SEREX identified RPA2 as the antigen associated with ischemic stroke and serum auto-antibodies against RPA2 elevates in stroke patients. RPA2-Abs could become a biomarker for the evaluation of ischemic stroke at risk.
Subject(s)
Antigens/metabolism , Gene Library , Recombinant Proteins/metabolism , Stroke/immunology , Aged , Antibodies/metabolism , Blotting, Western , Cohort Studies , Electrophoresis, Polyacrylamide Gel , Enzyme-Linked Immunosorbent Assay , Female , Humans , Immunohistochemistry , Male , Middle Aged , Peptides/metabolism , ROC Curve , Reproducibility of ResultsSubject(s)
Brain Injuries/therapy , Craniocerebral Trauma/therapy , Emergency Medical Services/standards , Intensive Care Units/standards , Neurosurgical Procedures/standards , Severity of Illness Index , Brain Injuries/complications , Brain Injuries/physiopathology , Craniocerebral Trauma/complications , Craniocerebral Trauma/physiopathology , Emergency Medical Services/methods , Humans , Japan , Neurosurgical Procedures/methodsSubject(s)
Neurosurgery/history , Periodicals as Topic/history , History, 20th Century , History, 21st Century , Humans , International Cooperation/history , International Educational Exchange/history , International Educational Exchange/trends , Journal Impact Factor/history , Neurosurgery/trends , Peer Review, Research/trends , Periodicals as Topic/trendsABSTRACT
A 4-year study (Japan Neurotrauma Data Bank) of the medical treatment of 1002 cases of traumatic brain injuries in Japan was conducted from 1998 to 2001 at 10 emergency medical centers. Patients with severe head injury were eligible for entry with a Glasgow Coma Scale score of 8 or less at admission. Patients who underwent craniotomy were also included. Children under 5 years old were excluded. An original data sheet with 392 items from multi-focal viewpoints, such as etiology of injury, pre-hospital care, initial treatment including neuro-intensive care unit, and surgical treatment, was created. The results show that the patient's age and mechanism of injury are the most important factors in the outcome.
Subject(s)
Brain Injuries/epidemiology , Brain Injuries/therapy , Databases, Factual , Adolescent , Adult , Aged , Aged, 80 and over , Child , Female , Humans , Japan/epidemiology , Male , Middle Aged , Treatment OutcomeABSTRACT
Cathepsin D is an aspartyl protease involved in protein catabolism and tissue remodeling which can be secreted from cancer cells. To identify a potential serum marker for gliomas, we investigated the gene expression levels of cathepsin D in 87 tissue samples and measured the protein concentrations in sera of glioma patients. The tissue samples consisted of 43 glioblastomas, 13 anaplastic astrocytomas, 22 astrocytomas, and 9 normal brain tissues. The results of real-time quantitative reverse transcription-PCR analysis showed that cathepsin D transcript levels became significantly higher as the glioma grade advanced (P = 0.0466, glioblastoma and anaplastic astrocytoma; P = 0.0008, glioblastoma and astrocytoma; P = 0.0271, glioblastoma and normal brain tissue; unpaired t test). Immunohistochemical analysis with anti-cathepsin D antibody revealed dense and spotty staining in the tumor cells with high transcript levels. The low expression of cathepsin D significantly correlated with long survival of the glioma patients. Furthermore, the glioblastoma patients with high gene expression of cathepsin D lived significantly shorter than those with low expression (P = 0.0104, Cox-Mantel log-rank test) and frequently had leptomeningeal dissemination (P = 0.0016, chi2 test). The multivariate analysis confirmed that the cathepsin D expression level was an independent predictor for short survival (P = 0.0102, Cox proportional hazard regression model). Measurement of the serum cathepsin D concentrations by ELISA showed a significant increase in the patients with high-grade gliomas as compared with the low-grade tumors (P = 0.0081, chi2 test). These results collectively suggest that cathepsin D could be a potential serum marker for the prediction of aggressive nature of human gliomas.
Subject(s)
Astrocytoma/enzymology , Biomarkers, Tumor/blood , Brain Neoplasms/enzymology , Cathepsin D/blood , Glioblastoma/enzymology , Astrocytoma/genetics , Astrocytoma/pathology , Biomarkers, Tumor/biosynthesis , Biomarkers, Tumor/genetics , Brain Neoplasms/genetics , Brain Neoplasms/pathology , Cathepsin D/biosynthesis , Cathepsin D/genetics , Gene Expression , Glioblastoma/genetics , Glioblastoma/pathology , Humans , Immunohistochemistry , Meningeal Neoplasms/enzymology , Meningeal Neoplasms/genetics , Meningeal Neoplasms/pathology , PrognosisABSTRACT
PURPOSE: Sendai virus (SeV), a murine parainfluenza virus type I, replicates independent of cellular genome and directs high-level gene expressions when used as a viral vector. We constructed a nontransmissible recombinant SeV vector by deleting the matrix (M) and fusion (F) genes from its genome (SeV/DeltaMDeltaF) to enhance its safety. We also estimated the therapeutic efficacy of the novel vector system against a rat glioblastoma model. EXPERIMENTAL DESIGN: We administered the recombinant SeV vector carrying the lacZ gene or the human interleukin-2 (hIL-2) gene into established 9L brain tumors in vivo simultaneous with peripheral vaccination using irradiated 9L cells. Sequential monitoring with magnetic resonance imaging was used to evaluate the therapeutic efficacy. RESULTS: We found extensive transduction of the lacZ gene into the brain tumors and confirmed sufficient amounts of interleukin 2 (IL-2) production by hIL2-SeV/DeltaMDeltaF both in vitro and in vivo. The magnetic resonance imaging study showed that the intracerebral injection of hIL2-SeV/DeltaMDeltaF brought about significant reduction of the tumor growth, including complete elimination of the established brain tumors. The (51)Cr release assay showed that significant amounts of 9L-specific cytotoxic T cells were induced by the peripheral vaccination. Immunohistochemical analysis revealed that CD4(+) T cells and CD8(+) T cells were abundantly infiltrated in the target tumors. CONCLUSION: The present results show that the recombinant nontransmissible SeV vector provides efficient in vivo gene transfer that induces significant regression of the established brain tumors and suggest that it will be a safe and useful viral vector for the clinical practice of glioma gene therapy.
Subject(s)
Brain Neoplasms/genetics , Brain Neoplasms/therapy , Gene Transfer Techniques , Glioblastoma/genetics , Glioblastoma/therapy , Interleukin-2/genetics , Interleukin-2/pharmacology , Sendai virus/genetics , Animals , Brain Neoplasms/veterinary , Disease Models, Animal , Genetic Engineering , Genetic Vectors , Glioblastoma/veterinary , Glioma/pathology , Gliosarcoma/pathology , Kidney/cytology , Macaca mulatta , Male , Rats , Rats, Inbred F344 , TransgenesABSTRACT
BACKGROUND AND PURPOSE: A previous investigation of the MR imaging findings in the midbrain reported expanded perivascular (PV) spaces in only the ponto-mesencepalic junction (PMJ) in 20% of healthy subjects, whereas pathologically expanding PV spaces have been reported at the mesencephalo-diencephalic junction (MDJ) as multi-lobulated, cystic lesions with signal intensity compatible with that of CSF that cause aqueductal stenosis. To clarify the anatomical distinctions between normally expanded and pathologically expanding PV spaces, we defined their distribution in the normal midbrain by using high-spatial-resolution MR imaging. METHODS: Heavily T2-weighted MR imaging was performed in 115 adult subjects with neurologic complaints without cerebral disease. Histologic studies were performed from two normal midbrain blocks. RESULTS: Expanded PV spaces were visible at the PMJ in 87% of subjects and at the MDJ in 63% of subjects. On axial images, ovoid or linear lesions with signal intensity compatible to CSF were present behind the cerebral peduncle at both the PMJ and MDJ. These areas varied from less than 1 mm to 5 mm (maximum diameter on coronal sections). Histologic studies confirmed the distribution of expanded PV spaces, as noted on MR images. CONCLUSION: This study, by using high-spatial-resolution MR imaging, revealed that expanded PV spaces were visible at the PMJ and MDJ. Our finding of expanded PV spaces normally present at the MDJ may be related to pathologically expanding PV spaces, which should be kept in mind as a differential diagnosis for intraparenchymal cystic lesions in the midbrain with signal intensity compatible to CSF.
Subject(s)
Magnetic Resonance Imaging , Mesencephalon/anatomy & histology , Adolescent , Adult , Aged , Diencephalon , Female , Humans , Magnetic Resonance Imaging/methods , Male , Middle Aged , Pons , Reference ValuesABSTRACT
To identify the protein markers that are clinically useful for predicting efficacy of anticancer agents, we investigated the correlation between the proteome profiling patterns and the in vitro chemosensitivity in human gliomas. The proteome of 93 surgical samples were analyzed with two-dimensional gel electrophoresis (2DE) and mass spectrometry. The in vitro chemosensitivities to 10 different kinds of anticancer agents (cyclophosphamide, nimustine, cisplatin, cytosine arabinoside, mitomycin C, peplomycin, adriamycin, etoposide, vincristine, paclitaxel) were measured by flow cytometric detection of apoptosis. We identified a set of 41 proteins that significantly affected the in vitro chemosensitivity to each category of anticancer agents. Many of the proteins that correlated with chemoresistance were categorized into the signal transduction proteins including the G-proteins. The present study showed that the proteome analysis using 2DE could provide a list of proteins that may be the potential predictive markers for chemosensitivity in human gliomas. They can also be direct and rational targets for anti-glioma therapy and be used for sensitization to the conventional chemotherapeutic regimens.
Subject(s)
Antineoplastic Agents/pharmacology , Apoptosis/drug effects , Biomarkers, Tumor/analysis , Brain Neoplasms/genetics , Brain Neoplasms/pathology , Glioma/genetics , Glioma/pathology , Proteome , Drug Resistance, Neoplasm , Electrophoresis, Gel, Two-Dimensional , Humans , Predictive Value of Tests , Prognosis , Signal TransductionABSTRACT
The objective of this study is to examine whether dipole modeling based on a realistic scalp-skull-brain head model (SSB/DT) is useful to localize the epileptogenic zone. Eight patients with surgically treated temporal lobe epilepsy were studied. Dipole locations and vector moments of ictal epileptiform activities were calculated by inverse solution methods. Accuracy of dipole locations were assessed by comparing with intracranial EEG. The patterns of ictal epileptiform activities were correlated with the dipole location and vector moment. Dipole locations of the peaks of ictal epileptiform activities estimated by SSB/DT showed good agreement with the epileptogenic foci determined by intracranial EEG. SSB/DT was able to discriminate between medial and lateral temporal epileptogenic foci. Two distinctive types of dipole vector moments, vertical and horizontal were noted. Vertical dipole vector moments corresponded to the medial temporal dipole source and horizontal dipole vector moments were corresponded to the lateral temporal dipole source. Useful clues to differentiate between medial and lateral temporal lobe epilepsy by the visual inspection of scalp EEG were found. SSB/DT is useful tool in the presurgical evaluation of patients with intractable epilepsy.
Subject(s)
Brain Mapping , Brain/physiology , Epilepsy/physiopathology , Models, Neurological , Scalp/physiology , Skull/physiology , Adult , Electroencephalography , Female , Head/physiology , Humans , Male , Middle Aged , Positron-Emission Tomography , Reproducibility of Results , Tomography, Emission-Computed, Single-PhotonABSTRACT
We report a case of ovarian hyperstimulation related to a gonadotroph adenoma in a 29-year-old woman. The patient presented with amenorrhea and large cystic ovaries. Her serum estradiol was markedly elevated (up to 31,100 pmol/l). Serum LH was low, but serum FSH and PRL were normal. Cranial magnetic resonance imaging study revealed a pituitary macroadenoma. After successful removal of the pituitary tumor, FSH, LH and estradiol normalized and fluctuated within normal ranges thereafter. The patient resumed regular cycles of menstruation and conceived spontaneously. During pregnancy, estradiol increased and FSH and LH decreased. The finding confirms restoration of negative feedback of estradiol on FSH and LH secretion. The pregnancy course was uneventful and enlargement of ovaries did not occur.
Subject(s)
Adenoma/metabolism , Adenoma/surgery , Follicle Stimulating Hormone/metabolism , Pituitary Neoplasms/metabolism , Pituitary Neoplasms/surgery , Pregnancy Outcome , Adenoma/complications , Adult , Amenorrhea/etiology , Estradiol/blood , Female , Follicle Stimulating Hormone/blood , Humans , Luteinizing Hormone/blood , Magnetic Resonance Imaging , Ovarian Cysts/diagnostic imaging , Ovarian Cysts/etiology , Ovarian Cysts/pathology , Ovarian Hyperstimulation Syndrome/etiology , Pituitary Neoplasms/complications , Pregnancy , UltrasonographyABSTRACT
OBJECT: The authors assessed the diagnostic value of 201Tl Cl single-photon emission computerized tomography (SPECT), performed after gamma knife surgery (GKS) for metastatic brain tumors in differentiating tumor recurrence from radiation injury. METHODS: Of 6503 metastatic brain tumors treated with GKS, 201Tl SPECT was required in 72 to differentiate between tumor recurrence and radiation injury. When the Tl index was greater than 5, the lesion was diagnosed as a tumor recurrence. When the index was < 3.0 it was called radiation injury. In cases with a Tl index between 3 and 5, 201Tl SPECT was repeated once per month until the Tl index was greater than 5 or less than 3. If the Tl index fluctuated between 3 and 5 for 2 months, the lesion was diagnosed as radiation injury. The final diagnosis was based on histological examination or clinical course. The sensitivity of the method was 91%; thus 201Tl SPECT is effective for differentiating between tumor recurrence and radiation injury in metastatic brain tumors treated with GKS. Caution is necessary, however, for the following reasons: 1) simple interinstitutional comparisons of Tl indices are not possible because measurement methods are institute specific; 2) steroid administration decreases the Tl index to a variable degree; and 3) a severe radiation injury lesion, as is often seen after repeated GKS or very high dose GKS, may have a Tl index greater than 5. CONCLUSIONS: Used with critical insight 201Tl Cl SPECT can be useful in distinguishing between tumor regrowth and radiation necrosis in patients with cerebral metastases.
Subject(s)
Brain Neoplasms/diagnostic imaging , Brain Neoplasms/secondary , Brain Neoplasms/surgery , Radiation Injuries/diagnostic imaging , Radiation Injuries/epidemiology , Thallium , Tomography, Emission-Computed, Single-Photon , Aged , Brain Neoplasms/pathology , Female , Humans , Magnetic Resonance Imaging , Male , Middle Aged , Neoplasm Recurrence, Local , Neoplasms, Second Primary , Radiation Injuries/pathologyABSTRACT
We report a 20-year-old man who developed a chronic subdural haematoma (CSDH) after riding a "giant" roller coaster. The patient had a past history of a subdural hygroma, diagnosed six weeks after a motorcycle accident. Three months after this accident, he rode on a roller coaster, but suffered no direct head trauma during the ride. Three weeks later, he developed a CSDH requiring surgical evacuation. Roller coaster riding, associated with high velocities and extreme acceleration/deceleration forces is a modern cause of CSDH in the young, which may be increasing due to ever-faster rides.
Subject(s)
Hematoma, Subdural, Chronic/etiology , Accidents , Accidents, Traffic , Adult , Brain/pathology , Glasgow Coma Scale , Hematoma, Subdural, Chronic/pathology , Hematoma, Subdural, Chronic/surgery , Humans , Magnetic Resonance Imaging , Male , Motorcycles , Neurosurgical Procedures , Subdural Effusion/pathologyABSTRACT
The authors prospectively treated 18 consecutive patients with low-grade oligodendroglial tumors without postoperative radiotherapy. The treatment strategy was as follows: follow-up after total resection and chemotherapy after subtotal resection or biopsy. All patients were alive and 17 patients (94%) were progression-free after a median follow-up of 4.7 years. The results suggested that radiotherapy could be postponed until clinical progression in the treatment of low-grade oligodendroglial tumors.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Brain Neoplasms/drug therapy , Oligodendroglioma/drug therapy , Adult , Aged , Biopsy , Brain Neoplasms/mortality , Brain Neoplasms/pathology , Brain Neoplasms/surgery , Combined Modality Therapy , Disease-Free Survival , Female , Follow-Up Studies , Humans , Life Tables , Male , Middle Aged , Neoplasm Recurrence, Local , Nimustine/administration & dosage , Oligodendroglioma/mortality , Oligodendroglioma/pathology , Oligodendroglioma/surgery , Procarbazine/administration & dosage , Prospective Studies , Survival Analysis , Treatment Outcome , Vincristine/administration & dosageABSTRACT
Cigarette smoking is known to be one of the risk factors of subarachnoid hemorrhage (SAH), yet the precise mechanism remains to be proved. Based on the hypothesis that smoke components might enhance protease activity in the arterial wall, we examined the proteinase activities of plasma from smoke-extract-injected rats. Rats were injected intraperitoneally with smoke extract and the protease activity in the plasma was examined by zymography in the presence or the absence of proteinase inhibitors. Metalloproteinase activity was measured using a synthetic substrate. Proteolytic activities of 80- and 100-kDa against gelatin and collagen type I-V were induced 6 h after the injection. Inhibition of the activity by a metalloproteinase inhibitor but not by serine, cysteine or aspartic protease inhibitors suggested that the proteinases can be attributed to metalloproteinases. Cleavage activity in plasma toward a synthetic metalloproteinase substrate also increased within 24 h after the injection of the smoke extract. The results indicate that the induction of plasma metalloproteinase activity by smoke extract might account for the causal role of smoking in the development of SAH.
Subject(s)
Metalloproteases/blood , Smoke/adverse effects , Animals , Collagen/metabolism , Collagenases/blood , Collagenases/metabolism , Edetic Acid/pharmacology , Gelatin/metabolism , Male , Metalloproteases/antagonists & inhibitors , Metalloproteases/metabolism , Rats , Rats, Wistar , Smoking/blood , Time Factors , NicotianaABSTRACT
Human small fragment nuclease (Sfn) is one of the cellular proteins that were reported to degrade small, single-stranded DNA and RNA. However, the biological role of Sfn in cellular response to various stressors such as UV-C (mainly 254 nm wavelength ultraviolet ray) remains unclear. We have examined whether modulation of human SFN gene expression affects cell survival capacity against UV-C-induced cell death, analyzing colony survival ability in UV-C-sensitive human RSa cells treated with short double-stranded RNA (siRNA) specific for SFN messenger RNA (mRNA). The expression levels of SFN mRNA in the siRNA-treated RSa cells decreased to about 15% compared with those in the control siRNA-treated cells. The siRNA-treated RSa cells showed lower colony survival and higher activity of caspase-3 after UV-C irradiation than the control siRNA-treated RSa cells. Furthermore, the removal capacity of cyclobutane pyrimidine dimers (CPD) in the siRNA-treated RSa cells decreased compared with the control siRNA-treated RSa cells. There was no difference in the colony survival and CPD removal capacity after UV-C irradiation between the control siRNA-treated RSa cells and mock-treated RSa cells. These results suggest that SFN expression is involved in resistance of RSa cells to UV-C-induced cell death through the roles it plays in the DNA repair process.
Subject(s)
Biomarkers, Tumor/genetics , Biomarkers, Tumor/metabolism , Exonucleases/genetics , Exonucleases/metabolism , Neoplasm Proteins/genetics , Neoplasm Proteins/metabolism , Ultraviolet Rays , 14-3-3 Proteins , Caspase 3 , Caspases/metabolism , Cell Death/drug effects , Cell Death/radiation effects , Cell Line , Exoribonucleases , Humans , Kinetics , Pyrimidine Dimers/metabolism , RNA Interference , RNA, Messenger/genetics , RNA, Messenger/metabolismABSTRACT
BACKGROUND AND PURPOSE: Perivascular (PV) spaces are known to distend and cause edema along the optic tract (OT) in pituitary-region tumors. Interstitial fluid may be retained in PV spaces when tumors block their drainage outlets to subarachnoid spaces. However, these spaces and their outlets have not been anatomically elucidated. Our purpose was to evaluate how often large PV spaces are present along the OT and demonstrate their superficial communication points to adjacent subarachnoid spaces. METHODS: We examined serial histologic sections of 10 hemispheric blocks obtained from cadavers without cerebral abnormality. RESULTS: Large PV spaces, 0.5-1.5 mm in maximum height, were always present along the middle portion of the OT. Perforation points of the largest spaces were noted at the medial sulcus of the OT in seven hemispheres and through the OT in three. CONCLUSION: Large PV spaces are present along the middle portion of the OT. Their communication point to adjacent subarachnoid spaces was histologically demonstrated. The locations and variations of the outlet of large PV spaces explain the clinical features of edemas; these findings anatomically support the hypothesis that blockage of the outlets to subarachnoid spaces may play a role in distending the PV spaces and in causing edema in pituitary-region tumors. Only MR imaging has revealed this change; further pathologic investigations are awaited.