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Interferon regulatory factor (IRF) genes encode a family of DNA-binding proteins that are involved in the transcriptional regulation of type-I interferon and/or interferon-inducible genes. We report here the characterization of LSIRF, a new member of the IRF gene family cloned from mouse spleen by the polymerase chain reaction using degenerate primers. LSIRF was found to encode a 51 kDa protein that shares a high degree of amino acid sequence homology in the DNA-binding domain with other IRF family members. LSIRF expression was detectable only in lymphoid cells. In contrast to other IRF genes, LSIRF expression was not induced by interferons, but rather by antigen-receptor mediated stimuli such as plant lectins, CD3 or IgM crosslinking. In in vitro DNA binding studies, LSIRF was able to bind to the interferon-stimulated response element (ISRE) of the MHC class I promoter. The expression pattern and DNA binding activities suggest that LSIRF plays a role in ISRE-targeted signal transduction mechanisms specific to lymphoid cells.

Purpose: This study was designed to investigate the sequential changes of the CBF in hypertensive putaminal hemorrhage and to attempt to correlate these data with the treatment and ADL., Method: The CBF of 28 patients, aged from 39-70 years-old without any past history of cerebral insult, was measured sequentially from the acute stage by the xenon-enhanced CT method. Regarding treatment, 11 were treated conservatively, while 11 underwent stereotactic aspiration and the remaining 6 had an evacuation of the hematoma by craniotomy., Results and Conclusion: 1. The CBF of the hemisphere, thalamus and cortex progressively decreased until 16 weeks after onset, and then recovered gradually. However, the reduction in the CBF continued until reaching the chronic stage at a 20-40% reduction level on both sides. 2. A negative correlation between the CBF and the hematoma volume was noted and in hematoma over 15ml in volume, the CBF always decreased below a level of 30ml/100g/min. 3. There was no correlation between the CBF and the hematoma extension to the internal capsule. 4. There was a significant correlation between the CBF and ADL. 5. A hematoma measuring less than 15ml should be treated conservatively. 6. In hematoma measuring more than 15ml, stereotactic aspiration proved to be more effective than other therapies not only for the recovery of the CBF but also for ADL.

The authors report the unusual case of an aneurysm arising from the extracranial portion of the left posterior inferior cerebellar artery (PICA). The patient was a 39-year-old woman who developed a subarachnoid hemorrhage. The hemorrhage was in the basal, ambient, and Sylvian cisterns, but not in the ventricles. There were no focal neurological deficits, and the clinical grading was 1. On cerebral angiograms, the PICA was found to originate from the vertebral artery as low as 17.9 mm below the foramen magnum and to enter into the spinal canal through the intervertebral foramina of C1-C2. The artery went up to the posterior fossa and had only the cranial loop with an absence of the caudal loop. The saccular aneurysm hung on the initial segment of the PICA and was located at the C1 level. The patient developed motor aphasia and hemiparesis on the right side 15 days after onset, and an infarction was disclosed in the boundary zones of the left parietal lobe on a computed tomographic scan. The aneurysm was successfully obliterated by a neck clipping 2 months later, and the patient was discharged in good condition. The literature discussing PICA aneurysms in the extracranial, as well as distal, portion is reviewed.

The SWI1, SWI2, and SWI3 proteins, which are required for regulated transcription of numerous yeast genes, were found also to be essential for rat glucocorticoid receptor function in yeast; the receptor failed to activate transcription in strains with mutations in the SWI1, SWI2, or SWI3 genes. Certain mutations in genes encoding components of chromatin, identified as suppressors of swi mutations, partially relieved the SWI- requirement for receptor function. Immunoprecipitation of glucocorticoid receptor derivatives from wild-type (SWI+) yeast extracts coprecipitated the SWI3 protein; such receptor-SWI3 complexes were not detected in swi1- or swi2- mutant strains, implying that a complex of multiple SWI proteins may associate with the receptor. Prior incubation of a Drosophila embryo transcription extract with the yeast SWI3-specific antibody inhibited receptor function in vitro whereas the antibody had no effect if added after initiation complex formation. Thus, positive regulation by the glucocorticoid receptor in vivo and in vitro appears to require its interaction, at an early step, with one or more SWI proteins.

To delineate the pathophysiology of periventricular hemodynamics in normal pressure hydrocephalus, we performed quantitative and three-dimensional measurements of cerebral blood flow (CBF) by using xenon-enhanced computed tomographic scans. Measurements were made on 7 patients in whom normal pressure hydrocephalus after subarachnoid hemorrhage had been confirmed by clinical improvement after shunting. We compared mean CBF values in the white matter and cortex of the frontal, temporal, parietal, and occipital lobes and in the thalamus before and after shunting, with an evaluation of dementia and the extent of ventricular dilation and periventricular lucency on computed tomographic scans. CBF returned to within normal limits in the white matter of the frontal and temporoparieto-occipital lobes. CBF restoration closely correlated with clinical improvement and reduction in ventricular dilation and periventricular lucency. We speculate that ischemia occurs initially in the periventricular white matter as a result of diffused cerebrospinal fluid and then extends of the cortex and to the thalamus, causing a "misery perfusion" state with neuronal dysfunction. Incomplete improvement of dementia and CBF in the cortex and thalamus may be explained by preexisting arteriosclerosis in aged patients, coexisting brain damage caused by subarachnoid hemorrhage and subsequent surgical insult in aneurysm patients, and delayed recovery of cortical function that has been secondarily impaired by the periventricular lesions.

To elucidate the pathophysiology of mental disturbances associated with chronic subdural hematoma, we performed quantitative and three-dimensional measurements of cerebral blood flow (CBF) on xenon-enhanced computed tomographic scans in 12 patients who had chronic subdural hematomas and manifested mental disturbances. In 2 patients who had no headache or hemiparesis, minimal mass effect, and severe multiple infarctions on computed tomographic scan, mentation did not improve after surgery. The CBF reduction was severe, and it further deteriorated after surgery. On the other hand, mentation improved to a varied extent in the other 10 patients, who had headache and/or hemiparesis and minimal, moderate, or severe mass effect and minimal or moderate multiple infarctions on computed tomographic scan. The CBF reduction was diffuse on both sides, but was more marked in the thalamus and putamen than it was in the cortex and subcortex. It was restored after surgery, but insufficiently. The restoration rate was statistically significant only in the thalamus, on both sides (with and without hematoma) (P less than 0.05). Dementia scores and CBF values after surgery were correlated on the side with the hematoma in the frontal cortex and thalamus (P less than 0.01) and in the hemisphere and temporoparietal cortex (P less than 0.05). There was no correlation on the side with the hematoma in the occipital cortex, putamen, and frontal and temporoparieto-occipital subcortices or on the side without the hematoma. The thalamus undergoes displacement and distortion by the hematoma, which in turn leads to changes in consciousness. Postoperative residual mental deficits consist primarily of dementia related to preexisting multiple infarctions.(ABSTRACT TRUNCATED AT 250 WORDS)

We demonstrate that the rat glucocorticoid receptor enhanced transcription in cultured Drosophila cells from Drosophila promoters linked to glucocorticoid response elements (GREs); promoters either containing or lacking a TATA box were rendered hormone inducible. Enhancement was dependent on the receptor, GREs, and the presence of an agonist ligand such as dexamethasone. The specific activities and relative efficacies of a series of potential ligands were generally similar in Drosophila and mammalian cells, except that dexamethasone mesylate, a potent antagonist in mammalian cells, was a strong agonist in Drosophila cells. A composite GRE, which mediates either positive or negative glucocorticoid regulation in animal cells depending on the presence and composition of the AP-1 transcription factor, conferred hormone-dependent enhancement, but not repression, in Drosophila cells. These results indicate that factors in addition to the receptor and GRE sequences participate as determinants of both signal transduction and transcriptional regulation by the glucocorticoid receptor, and that Drosophila cells carry functional homologs of many or all of those factors. Moreover, receptor activity can be exploited to obtain regulated gene expression in Drosophila.

A 64-year-old female was admitted with a 6-year history of right hemifacial spasm. Neurological examination and precontrast computed tomographic (CT) scanning showed no abnormality. Vertebral angiography disclosed, however, a small arteriovenous malformation (AVM) in the right cerebellopontine angle. A postcontrast CT scan demonstrated a high-density area in the right cerebellomedullary junction which appeared as a flow-void signal on magnetic resonance images. A right retromastoid craniectomy was performed to separate an enlarged and tortuous loop of the right anterior inferior cerebellar artery from the right facial nerve using a Teflon-felt sheet. The AVM was not excised. Postoperatively, she was completely free of hemifacial spasm.

A case of elevation of the petrous bone due to hyperplasia of the occipital bone presenting as hemifacial spasm is reported. A 44-year-old man sought treatment for twitching of the buccal muscles on the right side that progressed rapidly in severity within 2 weeks of the onset. The anatomical details of the petrous and occipital bones were delineated clearly by computed tomographic scans of a bone window level. Details of the brain stem were shown by magnetic resonance images. The bone anomaly was displayed more realistically by three-dimensional computed tomographic reconstructions. The faithful representation of structures with these radiological studies should be mandatory, to prepare the surgical planning of such a complicated bone anomaly.

We compared clinical symptoms with extent of brain shift on computed tomographic (CT) scans and quantitative and three-dimensional measurements of cerebral blood flow (CBF) on xenon-enhanced CT scans in 10 patients with chronic subdural hematomas. Five patients had only headache and minimal or no brain shift on a CT scan. The other five had hemiparesis and/or mental disturbance in addition to headache and moderate or severe brain shift on a CT scan. The mean hemispheric CBF decreased about 7% in patients with headache and about 35% in patients with hemiparesis and/or mental disturbance. It decreased also on the side without the hematoma. The CBF reduction was always more pronounced in the putamen and thalamus than in the cortex. On the contrary, the cortex CBF was mostly preserved or even elevated in both groups of patients. We speculate that CBF reduction in patients with a chronic subdural hematoma occurs initially in central cerebral areas like the basal ganglia and thalamus, and then extends to the entire hemisphere including the cortex as brain compression and displacement progress. Central cerebral area involvement might be more responsible for clinical symptoms than the cortex.

The mechanism by which a single factor evokes opposite regulatory effects from a specific DNA sequence is not well understood. In this study, a 25-base pair element that resides upstream of the mouse proliferin gene was examined; it conferred on linked promoters either positive or negative glucocorticoid regulation, depending upon physiological context. This sequence, denoted a "composite" glucocorticoid response element (GRE), was bound selectively in vitro both by the glucocorticoid receptor and by c-Jun and c-Fos, components of the phorbol ester-activated AP-1 transcription factor. Indeed, c-Jun and c-Fos served as selectors of hormone responsiveness: the composite GRE was inactive in the absence of c-Jun, whereas it conferred a positive glucocorticoid effect in the presence of c-Jun, and a negative glucocorticoid effect in the presence of c-Jun and relatively high levels of c-Fos. The receptor also interacted selectively with c-Jun in vitro. A general model for composite GRE action is proposed that invokes both DNA binding and protein-protein interactions by receptor and nonreceptor factors.

Transcription factor TFIIIC2 derived from human cells is required for tRNA-type gene transcription and binds with high affinity to the essential B-box promoter element of tRNA-type genes. Although 5S rRNA genes contain no homology with the tRNA-type gene B box, we show that TFIIIC2 is also required for Xenopus laevis 5S rRNA gene transcription. TFIIIC2 protected an approximately 30-base-pair (-10 to +18) region of a Xenopus 5S rRNA gene from DNase I digestion. This region, which spanned the transcription start site, included sequences that are highly conserved among eucaryotic 5S rRNA genes and have no homology with the B-box sequence of tRNA genes. Mutation of the TFIIIC2-binding site reduced transcription of the 5S rRNA gene by a factor of 10 in HeLa cell extracts. Methylation of C residues within the TFIIIC2-binding site interfered with binding of TFIIIC2. These results suggest a role of the TFIIIC2-binding sequence in 5S rRNA gene transcription. In addition, the 5S rRNA gene binding site and the tRNA-type gene B-box sequence did not compete with each other for binding to TFIIIC2 any better than did an unrelated DNA sequence, indicating that TFIIIC2 interacts with 5S rRNA genes and tRNA-type genes through separate DNA-binding domains or polypeptides.

Human cells expressing adenovirus E1A proteins transcribe transfected tRNA and adenovirus VAI genes at greater than 10-fold higher levels than uninfected HeLa cells. Here we show that the increased transcription observed in vivo is reflected in the in vitro transcriptional activity of cell extracts. Depletion of E1A protein from these extracts by immunoprecipitation with a monoclonal antibody did not diminish the activity, suggesting that E1A proteins do not stimulate transcription directly. Fractionation of the extracts by chromatography on phosphocellulose suggests that the higher activity of extracts of adenovirus-infected cells was due to increased activity of the transcription factor (TF) which is the limiting component required for specific initiation of tRNA and VAI transcription in extracts of uninfected HeLa cells, i.e. TFIIIC. Template commitment titrations further suggest that the increased TFIIIC activity was due to an increase in the concentration of active TFIIIC. On the basis of these results and recent genetic analyses of early adenovirus promoters, we suggest that E1A proteins stimulate transcription of adenovirus genes indirectly by increasing the effective in vivo concentration of the limiting cellular transcription factors required for their transcription.

A case of saccular aneurysm located at the PCA posterior temporal artery junction (E portion of PCA) was reported. A 35-year-old man was referred to us for surgical treatment of intracerebral hematoma in the right temporo-parietal lobes. On admission, the patient was somnolent and there was right oculomotor palsy, left homonymous hemianopsia and left hemiparesis. Left vertebral angiograms revealed a saccular aneurysm at the quadrigeminal segment of the posterior cerebral artery on the right. The hematoma was immediately evacuated by temporal corticotomy, and three weeks later, trapping of the aneurysm was performed through subtemporal approach. Postoperative course was uneventful. However, the left homonymous hemianopsia persisted. This was the only symptom which did persist. The incidence of PCA aneurysm is 1% in all cerebral aneurysms, or 15% in aneurysms of the posterior circulation. The majority of those are located at the junction proximal to the PCA-anterior temporal artery, or proximal to the PCA-posterior lateral choroidal artery junction. In the present case, the aneurysm was located more distally at the PCA-posterior temporal artery junction, and aneurysm at this site has been reported only six times in the literature. In addition to the present case, we reviewed 41 cases (42 aneurysms) in the literature, concerning the operative method and postoperative neurological deficits for the aneurysms of PCA. Neck clipping was performed in 23 cases without any further neurological deficits and trapping or proximal clipping of the aneurysms was performed in 16 cases, in which new neurological deficits developed in 3 cases.

Mammalian glucocorticoid receptors enhance transcription from linked promoters by binding to glucocorticoid response element (GRE) DNA sequences. Understanding the mechanism of receptor action will require biochemical studies with purified components. Enhancement was observed in vitro with derivatives of the receptor that were expressed in Escherichia coli, purified, and added to a cell-free extract from Drosophila embryo nuclei. Transcription from promoters linked to one or multiple GREs was selectively enhanced by as much as six times. The effect was weaker with only one GRE, and enhancement was abolished by a point mutation that inactivates the GRE in vivo.

Four cases of syringomyelia, each were considered to have different pathogenesis of syrinx and presented different clinical and radiological pictures, are reported. Case I was associated with Chiari I malformation and the syrinx communicated with the fourth ventricle through the central canal, case 2 was associated with Chiari II malformation and the syrinx was not communicated with the fourth ventricle, case 3 was thought to be traumatic and case 4 to be arachnoiditis due to unknown etiology. Metrizamide CT myelography was most valuable diagnostic technique to disclose the syringomyelic cavity and its extension. The cases except case 1 showed central opacification without via fourth ventricle, suggesting transneural migration CSF as shown by Aubin et al. Surgical treatment, therefore, was different in each case to obtain normal CSF dynamics. Case 1 was treated by suboccipital craniectomy, muscle plugging to the obex and syringo-subarachnoid shunt. In case 2 syringo-cisternal shunt was done in addition to suboccipital craniectomy. In case 3 syringocisternal shunt was done after laminectomy. In case 4 syringo-peritoneal shunt was performed. All but case 4 were obtained favorable result and case 4 was unfavorable except the disappearance of girdle sensation. For traumatic or inflammatory syringomyelia with tight adhesion between pia and arachnoid membrane in subarachnoid space, syringocisternal shunt was good way to obtain normal CSF dynamics and was expected to relieve the neurological deterioration.

We report the cases of two patients, each of whom had two separate angiographically demonstrable intracerebral arteriovenous malformations (AVMs). One patient had an intraventricular hemorrhage with AVMs in the basal ganglia and the insula on the left side, and the other had a pontine hemorrhage with AVMs in the pons and the occipital lobe on the right side. The AVMs in the former patient were removed totally without residual neurological deficit. We discuss the diagnostic problems of multiple intracerebral AVMs and stress the need for thorough neuroradiological evaluation so as not to miss an occult AVM. We also stress the necessity of total excision of all the lesions and point out several problems faced in surgery for AVMs.

The inhibition of transcription by RNA polymerase III in poliovirus-infected cells was studied. Experiments utilizing two different cell lines showed that the initiation step of transcription by RNA polymerase III was impaired by infection of these cells with the virus. The observed inhibition of transcription was not due to shut-off of host cell protein synthesis by poliovirus. Among four distinct components required for accurate transcription in vitro from cloned DNA templates, activities of RNA polymerase III and transcription factor TFIIIA were not significantly affected by virus infection. The activity of transcription factor TFIIIC, the limiting component required for transcription of RNA polymerase III genes, was severely inhibited in infected cells, whereas that of transcription factor TFIIIB was inhibited to a lesser extent. The sequence-specific DNA-binding of TFIIIC to the adenovirus VA1 gene internal promoter, however, was not altered by infection of cells with the virus. We conclude that (i) at least two transcription factors, TFIIIB and TFIIIC, are inhibited by infection of cells with poliovirus, (ii) inactivation of TFIIIC does not involve destruction of its DNA-binding domain, and (iii) sequence-specific DNA binding by TFIIIC may be necessary but is not sufficient for the formation of productive transcription complexes.

tRNA genes and adenovirus viral-associated (VA) genes are transcribed by RNA polymerase III. Transcription of these genes in vitro requires two protein fractions containing transcription factors designated TFIIIB and TFIIIC, in addition to RNA polymerase III. We report that the TFIIIC fraction derived from human cells in culture can be separated into two functional components, which we call TFIIIC1 and TFIIIC2. Both TFIIIC1 and TFIIIC2 fractions are required for in vitro transcription of the VA1 gene. In DNase I "footprinting" experiments, the TFIIIC2 fraction protects the internal control region termed the B block. Addition of the TFIIIC1 fraction extends the footprint over the internal control region called the A block. TFIIIC1 activity is the limiting transcription factor activity required for VA1 transcription in the crude extract. TFIIIC2 activity sediments as a large component of approximately 18 S, while TFIIIC1 activity sediments at approximately 9 S. These data indicate that the two activities are unique components and when added together reconstitute TFIIIC activity.

We report a calcified chronic subdural hematoma which ruptured intracerebrally forming an acute subcortical hematoma in the frontal lobe in a 59-year-old woman with long-standing liver cirrhosis. Both hematoma cavities communicated each other through a small defect within the inner membrane of the subdural hematoma. The content of both hematomas was identical and was of a clay-like clot. The inner membrane around this communication consisted of thick, very vascular granulation tissue with many hemosiderin deposits and was tightly adherent to the cortex. We speculated that a fresh bleeding into the granulation tissue resulted in formation of a subcortical hematoma through a rupture of the inner membrane. Disseminated intravascular coagulation likely played an important role in this unusual condition.

Transcription factor IIIC2 (TFIIIC2), together with other transcription factors (TFIIIB and TFIIIC1), is required for the in vitro transcription of tRNA and adenovirus VA genes by RNA polymerase III. Previous studies have shown that TFIIIC2 is a high molecular weight (approximately 500,000) protein which binds with high affinity to the B-box promoter element of tRNA-type genes. A polypeptide of Mr approximately 250,000 is in close association with DNA in the specific complex between TFIIIC2 and the B-box promoter element. Here we describe the purification of TFIIIC2 by a factor of approximately 25,000 from nuclear extracts of HeLa cells by ionic exchange, affinity, and hydrophobic chromatography and sedimentation velocity centrifugation. The most purified fractions contain polypeptides of approximately 230 kDa (corresponding to the polypeptide which can be cross-linked to VA1 DNA), 110, 100, 80, and 60 kDa which co-sediment with TFIIIC2 B-box specific binding and in vitro transcriptional activities.

Interaction between the B-block region of adenovirus VA1 DNA and the human RNA polymerase III transcription factor (TFIII) C2 was analyzed using a gel DNA-binding assay. The retarded band corresponding to the specific complex between TFIIIC2 and the regulatory B-block region was identified by DNase I footprint analysis, competition experiments, and gel shift assays using mutated and truncated virus-associated (VA) 1 DNA probes. The equilibrium constants for the binding reaction with the complete VA1 gene were determined. TFIIIC2 was found to bind to non-specific DNA sequences with a relatively low affinity (equilibrium constant Kn = 6 x 10(4) M-1), and to the B-block sequence with a high affinity (specific constant Ks = 2 x 10(11) M-1). Assuming one site per molecule, the total concentration of binding sites [C0] in the TFIIIC2-containing fractions ranged between 0.6 and 1.6 x 10(-10) M. This corresponded to 1500 TFIIIC2 molecules extracted per 293 cell. Sedimentation analysis of TFIIIC2 on a sucrose gradient showed both VA1 DNA binding activity and in vitro transcription activity cosedimenting with an apparent coefficient of 17-18 S, consistent with a molecular weight of 400-500 kDa. UV cross-linking of a 5-bromo 2'-deoxyuridine-containing, 32P-labeled VA1 probe with the TFIIIC2 fraction, followed by DNase I digestion and analysis by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, revealed a single 32P-labeled band migrating as a 250-kDa polypeptide. Compared with the sedimentation data, this result suggests that native TFIIIC2 may be a dimer of the approximately 250-kDa polypeptide.