[Diagnosis and therapy of headache due to chronic subdural hematoma].
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Biomedical subjects
Publications and source records attributed to T Yoshimoto.
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DDD/1 (DDD) mice were characterized by marked paucity of T cells in lymph nodes (LN). In DDD-Mtv-2/Mtv-2 (DDD-Mtv-2) congenics, T cells were 4- to 18-fold increased depending on ages but B cells doubled at the most. Thymus weight also increased. In DDDfDDD-Mtv-2, DDD neonatally infected with Mtv-2-derived exogenous MMTV (MMTV-2), neither LN cells nor thymus weight increased. The V beta 5+ and V beta 8+ T cell contents in LN were practically the same among three strains. The Mtv-2-induced expansion of LN T cells was polyclonal and appeared indigenous to DDD mice. Both Mtv-2 and MMTV-2 induced progressive age-dependent deletion of V beta 14+CD4+ LN cells. Mtv-2 but not MMTV-2 caused deletion of V beta 14+CD8+ LN cells and mature V beta 14+CD4+ thymocytes. Thus, Mtv-2- and MMTV-2-induced V beta 14+ T cell deletion may reflect intrathymic and peripheral elimination, respectively. The absence of I-E gene expression in DDD indicates that V beta 14+ T cell deletion advances independently of I-E molecules in this experimental system.
The MHC class II I-A(s) positive B cell lymphomas reticulum cell sarcoma (RCS) that arise in > 90% of SJL mice by the age of 12 months have superantigen-like stimulating properties. In the present study, therefore, RCS cell lines were examined for abnormal expression of endogenous mouse mammary tumor virus (MMTV) proviruses. Extraordinarily high expression of a 1.8 kb mRNA hybridizing with the long terminal repeat (LTR) of MMTV was found in both primary lymphomas and in vitro RCS lines, but not in an SJL B cell lymphoma, NJ101, that does not stimulate syngeneic T cells, or in LPS activated SJL B cells. A cDNA was cloned from cRCS-2 and sequenced. A 31mer oligonucleotide probe, prepared based on the unique C-terminal sequence of this RCS-Mtv LTR, detected the 1.8 kb mRNA in all RCS lymphomas, while a similar probe for the C-terminal sequence of Mtv-8 LTR hybridized with the larger mRNA present in normal B cells and in NJ101. Preincubation with 19mer antisense S-oligonucleotides, prepared based on the sequences of the first two potential translation initiation sites common to both Mtv-8 and the RCS-Mtv LTR, significantly reduced the ability of RCS cells to stimulate syngeneic T cells. Moreover, transfection of NJ101 cells with the cloned RCS-MMTV cDNA conferred V beta 16 T cell stimulating properties on to these cells. It is concluded that expression of the product of this MMTV-LTR mRNA provides RCS with the strong T cell stimulating properties that it needs for its growth. These results thus identify a novel oncogenic property of MMTV-LTR.
Cerebral blood flow in seven infants with extracerebral fluid collections was investigated using single photon emission computed tomography (SPECT) with 123I-N-isopropyl-p-iodoamphetamine. Early and delayed SPECT imaging was carried out. Areas of hypoperfusion were observed in five cases. The watershed zone of the major cerebral arteries or the territory of the anterior cerebral arteries were common areas of low perfusion. The hypoperfusion area was redistributed in two cases with intracranial hypertension. Subduroperitoneal shunts produced improvement of clinical symptoms in these cases. Hypoperfusion without redistribution was observed in three patients. In these areas, permanent tissue damage caused by a primary disease existed. Normal circulation patterns were observed in two patients. They showed normal development and follow-up CT revealed a decrease in the size of the extracerebral fluid collection. Measurement of regional cerebral blood flow may be helpful in considering surgical indications and in following up extracerebral fluid collection in infants.
A 9-day-old female presented with a large infra- and supratentorial medulloblastoma was treated by surgery, irradiation and chemotherapy. The infant suffered from vomit a few days after birth. She was hospitalized shortly thereafter, when head enlargement was noted. A CT scan taken on admission disclosed a large mass lesion in the cerebellum, extending to the pineal portion, and marked hydrocephalus. At the age of 14 days, the patient underwent ventriculoperitoneal shunting. When she was 67 days old, the tumor was radically resected. The histopathological diagnosis was medulloblastoma. Post operatively, she was irradiated with 30 Gy to the whole brain and 20 Gy to the tumor site. As chemotherapy, ACNU, 1-(4-amino-2-methyl-5-pyrimidinyl-3-(2-chloroethyl)-3-nitrosourea 1 mg/kg was administered twice per 6 weeks. On discharge at 7 months, her only neurological deficit was nystagmus. One week later, she could not move her legs and was readmitted. A CT scan showed no intracranial changes, but the spinal cord was swollen at Th12-L5 level. Myelography demonstrated a filling defect at the L3-5 level. Following irradiation of the spinal cord, the paraparesis gradually improved. However, her general status was deteriorating and a follow up CT scan revealed recurrence of the intracranial tumor. The patient died at the age of 9.3 months which is longer survival time than previous reported one. Neonatal brain tumors are rare, and there have been only 24 cases of neonatal medulloblastoma. The prognosis for these patients is extremely poor, regardless of treatment. Surgery, radiation and chemotherapy for neonatal medulloblastoma are discussed.
Using positron emission tomography and radio-high performance liquid chromatography, the accumulation of 2'-deoxy-5-18F-fluorouridine in the brain tumors and plasma pharmacokinetic parameters were investigated in 20 patients. High accumulation of the tracer in high grade gliomas and meningiomas and very rapid degradation of the tracer in the plasma were found. Very large variations were observed in both tumor accumulation and pharmacokinetic data. The tumor accumulation, however, did not correlate with any of the plasma pharmacokinetic parameters: area under the plasma concentration-time curve, mean residence time, total body clearance and steady-state volume of distribution. The results suggest that the accumulation of the tracer reflects the metabolic activity of the brain tumor tissues and that the effect of the rapid metabolic change in the tracer in the plasma on the tumor accumulation may be minor.
Tethered cord syndrome associated with Turner's syndrome in an 8-year-old boy is reported. Complicated mesodermal anomalies were observed from birth: a ventricular septal defect, hydronephrosis, agenesis of the sacrum, hypospadias, and anal atresia. Male external genitalia and a 45XO/46XY mosaic chromosome pattern were recognized, and a diagnosis of male Turner's syndrome was made. In the course of development, aggravation of a neurogenic bladder and a gait disturbance appeared. Low spinal conus and thickened filum were observed on MRI, and an operation of untethering was performed. The possible genesis of the thickened filum in systemic mesodermal anomalies of Turner's syndrome is discussed.
In order to evaluate the effect of extracranial-intracranial (EC/IC) bypass surgery for the patients with ischaemic cerebrovascular disease, fourteen patients were studied for cerebral blood flow (CBF), oxygen extraction fraction (OEF) and cerebral metabolic rate of oxygen (CMRO2) before and after EC/IC bypass using positron emission tomography (PET) and 15O steady state technique. Six patients with carotid lesion received superficial temporal artery (STA)-middle cerebral artery anastomosis, and eight patients with vertebro-basilar lesion underwent STA-superior cerebellar artery anastomosis. In both groups of patients with carotid and vertebro-basilar lesion, significant increase of CBF and decrease of OEF were observed following surgical revascularization. Especially in patients with vertebro-basilar lesion, remarkable improvements were observed not only in the cerebellum but also in the cerebral cortex. In addition, the cases with preoperative higher OEF showed marked increase of CBF and decrease of OEF. It was suggested that EC/IC bypass can be effective when pre-operative uncoupling between cerebral circulation and metabolism are marked and PET study provides useful information for selecting the appropriate candidates for EC/IC bypass surgery.
Thrombin has multiple functions, including its function as a key enzyme during blood coagulation and other physiologic activities. We studied brain tissue reactions to thrombin that might be present in the central nervous system (CNS) following injury. Thrombin and three different types of controls--buffer, albumin, and plasmin--were individually infused into the rat caudate nucleus by a continuous osmotic mini-pump. Brains were examined by conventional histologic and immunohistologic techniques. Antibodies for bromodeoxyuridine (BrdU), glial fibrillary acidic protein (GFAP), vimentin, and laminin were employed to assess the infiltration of inflammatory cells, proliferation activity of cells, and reaction of astrocytes and mesenchymal cells, respectively. The number of inflammatory cells, number of BrdU-positive cells, area and number of vimentin-positive astrocytes, and the area of GFAP-positive astrocytes were quantitatively analyzed. Thrombin caused infiltration of inflammatory cells, proliferation of mesenchymal cells, induction of angiogenesis, and an increase in vimentin-positive reactive astrocytes. These histologic changes caused by thrombin infusion resembled the inflammation, scar formation, and reactive gliosis in the CNS following injury. These results suggest that thrombin may play an important role in inflammatory responses to CNS injury since thrombin is one of the blood borne factors that may interact with brain tissue after CNS injury. The data further suggest that the therapeutic application of antithrombin agents for CNS injury suppresses inflammation and the excessive gliosis and scar formation, which are barriers to neuronal regeneration.
The active site structure of the Zn-containing neutral protease from Bacillus subtilis var. amylosacchariticus (BANP) was predicted by computer-aided modeling on the basis of the three-dimensional structure of thermolysin (TLN). As expected from the high homology in amino acid sequence of the two enzymes, the overall folding of BANP was very similar to that of TLN. Glu144, Tyr158, and His228 of BANP were located near the active site Zn ion, to which three amino acid residues, His143, His147, and Glu167, were coordinated. This model is supported by the previous results that chemical modifications of Tyr158 and photooxidation of His228 of BANP markedly affect the proteolytic activity of the enzyme. Interestingly, BANP was found to be significantly less sensitive to metalloprotease inhibitors such as phosphoramidon and talopeptin. From a comparison of the enzyme-inhibitor complex models between BANP and thermolysin, it is suggested that replacement of Thr129 in TLN by Phe130 in BANP is related to difference in inhibitor sensitivity between BANP and TLN.
The pyroglutamyl peptidase [EC 3.4.11.8] gene from Bacillus amyloliquefaciens was cloned and expressed in Escherichia coli DH1. The transformant of E. coli DH1 harboring plasmid pBPG 1 with a 2.1 kb chromosomal DNA fragment showed 80-fold higher activity than B. amyloliquefaciens. The nucleotide sequence of a 0.9 kb fragment that contains the promoter and the mature protein coding region was determined by the dideoxy chain-termination method. An open reading frame of 648 bp starting with an ATG methionine codon was found, which encodes a protein of 215 amino acid residues with a deduced molecular weight of 23,286. The enzyme has two cysteine residues (Cys68 and Cys144) per subunit molecule. Substitution of Cys144 with Ser by site-directed mutagenesis resulted in a complete loss of the activity, while that of Cys68 with Ser did not affect the activity at all. This result and titration with DTNB suggest that Cys144 is concerned in the catalytic action and Cys68 is located inside the enzyme. The expressed enzyme was purified to homogeneity by hydrophobic chromatography on a Toyopearl HW-65C column and crystallization, with an activity recovery of 42.7%. The enzyme was most active at pH 6.5 and stable at pH 7.0-9.0. Its molecular weight was estimated to be 51,000 by gel filtration, suggesting it to be a dimer. Big crystals of the wild and PCMB-modified enzymes were obtained by the hanging drop method.
A strain of Aeromonas hydrophila was found to show prolyl endopeptidase activity. The enzyme gene was cloned and expressed in Escherichia coli JM83. A 12 kbp EcoRI fragment containing the enzyme gene was subcloned at the HincII site of pUC19 to construct plasmid pAPEP-3 with a 3.5 kbp insert. E. coli JM83 transformed with this plasmid showed about 100-fold higher activity than the parent Aeromonas. Analysis of the nucleotide sequence of the insert revealed that the mature enzyme-encoding sequence starts just after the ATG initiation codon of the open reading frame. The enzyme was a single polypeptide composed of 689 amino acid residues with a molecular weight of 76,383. It showed properties very similar to those of Flavobacterium prolyl endopeptidase, except that the isoelectric point was 5.5. The amino acid sequence was 56 and 41% homologous to those of Flavobacterium and porcine brain prolyl endopeptidases, respectively. From a survey of sequence homology with other members of the prolyl endopeptidase family, the amino acid residues involved in the catalytic triad were deduced to be Ser-537, His-656, and Asp-512 (or Asp-621).
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The murine cationic amino acid transporter is also the receptor for murine ecotropic leukemia retrovirus (MuLV-E). Recently, we have cloned a human gene (H13) homologous to the murine ecotropic retroviral receptor (ERR). Although the human homolog is very similar to murine ERR in sequence (87.6% amino acid identity) and structure (14 transmembrane-spanning domains), the human protein fails to function as a receptor for MuLV-E. To identify amino acid residues critical for MuLV-E infection, we took advantage of this species difference and substituted human H13 and murine ERR amino acid residues. Mouse-human chimeric receptor molecules were generated by taking advantage of using common restriction sites. These studies demonstrated that extracellular domains 3 and/or 4 contain the critical amino acid residues. Oligonucleotide-directed mutagenesis was then used to create 13 individual ERR mutants containing one or two amino acids substitutions or insertions within these two extracellular domains. Substitution of as few as one amino acid residue (Tyr) at position 235 in ERR with the corresponding H13 amino acid residue Pro abrogates the ability to function as a receptor for MuLV-E infection. Conversely, substitution of just two amino acid residues at positions 240 and 242 or 242 and 244 in H13 with the corresponding amino acid residues in ERR endows H13 with the ability to function as the receptor. This observation can be utilized to significantly improve the safety of retrovirus-mediated gene therapy in humans.
The authors report a rare case of cervical spinal neurinoma in a patient who presented with symptoms originating from hydrocephalus. Her symptoms improved after a ventriculoperitoneal shunt was inserted, although progressive quadraparesis appeared when she began to walk. Magnetic resonance imaging revealed a cervical tumor. When it was removed, the patient's quadraparesis improved. Associated spinal tumors should be considered in the treatment of hydrocephalus of unknown origin.
The clinical courses of four patients with occult spinal dysraphism who were also found to have anorectal malformations and tethered cord syndrome are evaluated in this report. These patients were among 27 patients with occult spinal dysraphism treated in the Division of Neurosurgery of Tohoku University School of Medicine during the last 3 years. All four patients experienced urinary disturbances early in life, and initially, these disturbances were considered to be caused by urogenital malformations. As a result, treatments were delayed. Only one patient with male Turner's syndrome exhibited mental retardation. Other symptoms, such as sensory disturbance and pain in the lower extremities, became apparent from complaints by the patients without atresia ani. When surgery was performed earlier in our patients with occult spinal dysraphism, the outcome was better. We believe in early surgery for tethered cord syndrome, although there is no consensus for the timing of this surgery. Unfortunately, the diagnosis of tethered cord syndrome was delayed in our four patients. However, because occult spinal dysraphism and anorectal malformations seem to be closely related, the presence of anorectal malformations may result in an earlier diagnosis of tethered cord syndrome.
The authors encountered a rare case of multilobular cavernous angioma arising from the paraventricular region in an infant. Total resection of the angioma, which was 8 cm in diameter, was performed. The patient showed no neurological deficit. Although 22 cases in infants have previously been reported, this is the largest cavernous angioma and it is especially rare because of its multilobular configuration.