Long Duration of Erythrocyte Hypoplasia after Bone Marrow Transplantation

Bone marrow transplantation was performed on a 15 year old girl with chronic myelogenous leukemia. The bone marrow was obtained from her younger sister, who was human leukocyte antigen haplo-identical but major ABO incompatible. As a result, the condition of pure red cell aplasia (PRCA) persisted over a long period of time. In order to overcome major ABO incompatibility, erythrocytes were eliminated from the bone marrow graft before transplantation, and methotrexate and cyclosporine (CsA) were used to prevent graft-versus-host disease (GVHD). Administration of erythropoietin proved ineffective. B19 parvovirus infection could not be detected during that time. Agglutinin titers decreased to less than fourfold in parallel with the recovery of erythrocytes. Reports on similar PRCA have been limited to cases of transplantation with ABO incompatibility and cases where CsA was administered to prevent GVHD. This suggests that ABO incompatibility and CsA might be related to the development of PRCA.     

The mechanism of growth-regulation of glioma cells by trapidil

Summary Trapidil is a PDGF antagonist that can inhibit the proliferation of the PDGF-producing glioma cells, U251MG. As the mechanism of growth-regulation by trapidil remains unclear, we studied its effect on the growth of U251MG cells. We performed a cell cycle analysis and examined the intracellular transduction pathway and oncogene expression in serum-stimulated glioma cells with or without trapidil.After the serum starvation for 3 days, glioma cell proliferation was stimulated by the addition of serum. Cell cycle analysis showed that cell cycle perturbations induced by trapidil included a decreased transition rate from G₀-G₁ to S phase, suggesting that some metabolic event is required for progress through the G₀-G₁ phase and that this event is sensitive to trapidil. Internal signal transduction mechanisms are central in the molecular control of cell growth. One such regulator is the protein kinase C(PKC) system and the c-fos gene is likely to be a direct target of intracellular signal transduction pathways. Therefore, we hypothesize that the intracellular PKC activity and c-fos expression of the trapidil-treated cells are suppressed. We posit that trapidil affects the intracellular signal transduction pathway PKC activity and c-fos expression in cells stimulated with serum containing growth factors.     

Prognostic factors in patients who survived more than 10 years after undergoing surgery for metastatic brain tumors: report of 5 cases and review of the literature

BACKGROUND: Although the overall prognosis of patients with metastatic brain tumors is dismal, a small number survive longer than 10 years after craniotomy. We report 5 patients who survived for more than 10 years after undergoing treatment for metastatic brain tumor. METHODS: The 5 patients who survived for more than 10 years after undergoing craniotomy were among 56 consecutively treated patients with solitary metastatic brain tumors. We retrospectively examined their clinical course, treatment, and variables associated with their longer survival and compared these 5 patients with other reported cases of metastatic brain tumor. RESULTS: The histologic tumor types and the sites of origin of the primary tumor varied: two were from lung cancer and one each was from colon cancer, renal cell, and cervical carcinoma of the uterus. Common features among the long-term survivors were: systemic disease was absent, the metastatic tumor was located in the non-eloquent area of the non-dominant hemisphere, they were in good neurologic condition before surgery, there was a long interval between the diagnosis and treatment of the primary lesion and the diagnosis of the brain metastasis, and the patients received postoperative irradiation/chemotherapy. CONCLUSION: Aggressive surgical treatment may be justified in young patients with a solitary metastatic brain tumor, as long as they are free of active systemic metastases.     

Aneurysm originating from the fenestration of the posterior cerebral artery: case report

OBJECTIVE AND IMPORTANCE: A rare case of an aneurysm arising at the fenestration of the P2 segment of the posterior cerebral artery is reported. CLINICAL PRESENTATION: A 37-year-old man presented with severe headache and disturbance of consciousness. Computed tomographic scanning showed diffuse subarachnoid hemorrhage. Cerebral angiography revealed an aneurysm at the fenestration of the P2 segment of the right posterior cerebral artery. The aneurysm was located at the middle portion of the lower trunk of the fenestration. An unruptured arteriovenous malformation was incidentally found in the right thalamus. INTERVENTION: A right frontotemporal craniotomy with orbitozygomatic osteotomy was made, and the aneurysm was successfully clipped. One year after the operation, gamma knife surgery was performed for the right thalamic arteriovenous malformation. CONCLUSION: This is the first reported case of an aneurysm originating from the middle portion of a fenestrated posterior cerebral artery.     

Eleven novel single nucleotide polymorphisms in the NR1I2 (PXR) gene, four of which induce non-synonymous amino acid alterations

Eleven novel single nucleotide polymorphisms (SNPs) were found in the NR1I2 (PXR/SXR) gene from 205 Japanese subjects. The detected SNPs were as follows: 1) SNP, MPJ6_1I2001; GENE NAME, NR1I2; ACCESSION NUMBER, AF364606; LENGTH, 25 bases; 5'-TTTCTACCTCTAC/TTATTGAAAGGGC-3'. 2) SNP, MPJ6_1I2004; GENE NAME, NR1I2; ACCESSION NUMBER, AF364606; LENGTH, 25 bases; 5'-AGGCCCAAATGTG/AAGTGATGCATAG-3'. 3) SNP, MPJ6_1I2007; GENE NAME, NR1I2; ACCESSION NUMBER, AF364606; LENGTH, 25 bases; 5'-TGCCAGGCCTGCC/TGCCTGCGCAAGT-3'. 4) SNP, MPJ6_1I2008; GENE NAME, NR1I2; ACCESSION NUMBER, AF364606; LENGTH, 25 bases; 5'-GAGTGAGCAGTGG/CGCGCGCGGGCGG-3'. 5) SNP, MPJ6_1I2010; GENE NAME, NR1I2; ACCESSION NUMBER, AF364606; LENGTH, 25 bases; 5'-CAGAGGAGCAGCG/AGATGATGATCAG-3'. 6) SNP, MPJ6_1I2011; GENE NAME, NR1I2; ACCESSION NUMBER, AF364606; LENGTH, 25 bases; 5'-CTGGAAGTGGCCA/GGGAGGTTCAAAG-3'. 7) SNP, MPJ6_1I2013; GENE NAME, NR1I2; ACCESSION NUMBER, AF364606; LENGTH, 25 bases; 5'-TCTTCCTCTCGCC/TCCCAACTTCTGG-3'. 8) SNP, MPJ6_1I2017; GENE NAME, NR1I2; ACCESSION NUMBER, AF364606; LENGTH, 25 bases; 5'-ATTGAATGCAATC/TGGCCCCAGCCTG-3'. 9) SNP, MPJ6_1I2018; GENE NAME, NR1I2; ACCESSION NUMBER, AF364606; LENGTH, 25 bases; 5'-GGTGAGCACAGCA/GGGGGGTGAGGAC-3'. 10) SNP, MPJ6_1I2019; GENE NAME, NR1I2; ACCESSION NUMBER, AF364606; LENGTH, 25 bases; 5'-GAGCTCCGCAGCA/GTCAATGCTCAGC-3'. 11) SNP, MPJ6_1I2021; GENE NAME, NR1I2; ACCESSION NUMBER, AF364606; LENGTH, 25 bases; 5'-GGTGACACCTCCG/AAGAGGCAGCCAG-3'. The frequencies were 0.0293 for MPJ6_1I2021, 0.0073 for MPJ6_1I2011, and 0.0024 for the other 9 SNPs. All SNPs were found as heterozygous. Among these SNPs, MPJ6_1I2007, MPJ6_1I2010, MPJ6_1I2017 and MPJ6_1I2019 induce non-synonymous amino acid alterations (R98C, R148Q, R381W and I403V, respectively, in PAR1).     

A comparison of voluntary salt-intake behavior in Nax-gene deficient and wild-type mice with reference to peripheral taste inputs

The Na(x) channel, a subfamily of voltage-gated sodium channels, is thought to be a specific sodium receptor in the central nervous system. Our previous study revealed that Na(x)-gene-deficient mice consumed excessive amounts of NaCl even under water-deprived conditions. In the present study, to investigate whether the peripheral taste inputs are involved in the abnormal intake of salt in Na(x)-deficient mice (homo), voluntary intake of various taste solutions in homo and wild-type mice (wild) was examined under non-deprived conditions. Homo showed a higher preference for 0.15 M NaCl solution than wild. Preference ratios for other basic tastants were identical between groups. Transection of the chorda tympani (CT) or the glossopharyngeal (GP) nerve had little effect on salt-intake behavior in homo and wild. Although combined transection of the superior laryngeal (SL) and GP nerves decreased NaCl intake in homo but not in wild, there were no differences in preference ratios for NaCl in homo before and after SL+GP transection. On the other hand, preference ratios for NaCl in wild tended to increase after combined SL and GP transection. Consequently, preference ratios for NaCl after SL+GP transection were no different between homo and wild. While electrophysiological responses of the CT and the GP to various taste solutions were indistinguishable between homo and wild, those of the SL to NaCl in homo were smaller than those in wild only at lower concentrations (0.01 and 0.03 M). Thus, chemosensory inputs from the oro-pharyngeal regions had little effect on abnormal salt intake in homo, if any. From these results, it is suggested that the higher preference for NaCl in homo is mainly due to the lack of Na(x) channels in the central nervous system.     

Analysis of homozygous deletion of the p16 gene and correlation with survival in patients with glioblastoma multiforme

OBJECT: One of the most frequent genetic abnormalities found in patients with glioblastoma multiforme (GBM) is homozygous deletion of the p16 tumor suppressor gene. The authors investigated whether this deletion is associated with prognosis in patients with GBM. METHODS: In 46 adult patients with supratentorial GBM, homozygous deletion of the p16 gene in tumor DNA was examined using the multiplex polymerase chain reaction assay. The deletion was confirmed in 14 (30.4%) of 46 patients, eight (30.8%) of 26 men and six (30.0%) of 20 women. Cox proportional hazard regression analysis, adjusted for age at surgery, the Karnofsky Performance Scale score, extent of resection, and the MIB-1 labeling index. revealed that homozygous deletion of the p16 gene was significantly associated with overall survival and progression-free survival in men, but not in women. CONCLUSIONS: The results of this study suggest that p16 homozygous deletion is a significant unfavorable prognostic factor in male patients with GBM.     

Endoscopic telerobotics for neurosurgery: preliminary study for optimal distance between an object lens and a target

To overcome limited maneuverability and procedures in the endoscopic neurosurgery, and to utilize its maximum potential ability, the HUMAN (hyper-utility mechatronic assistant) system has been developed. The system has a rigid three-dimensional endoscope with built-in three guiding-manipulators completely controlled as a slave robot by a surgeon in a remote place. To use this system most efficiently, we investigated the suitable distance between an object lens of the endoscope and a target. Actual working territory (AWT) and actual working angle (AWA) of the forceps in the endoscopical operative field (EOF) were measured by changing the distance between the lens and the target. AWT ratio (AWT/EOF) and AWA ratio (AWA/360) decreased from 58% to 12% and increased from 39% to 85% respectively as the distance became longer. When the distance exceeds 13 mm, AWA did not increase more than 85%, and AWT kept decreasing. For the effective use of the system, the optimal distance between the lens and the target should be within 13 mm, and the system will demonstrate its ability to the maximum at the distance of 8mm.     

Increased expression of manganese superoxide dismutase is associated with that of nitrotyrosine in myopathies with rimmed vacuoles

Oxidative stress has been suggested as one of the pathogenetic mechanisms of inclusion body myositis (IBM). To study the role of antioxidant enzymes in myopathies with rimmed vacuoles, we examined expressions of copper, zinc superoxide dismutase (Cu, Zn-SOD) and manganese superoxide dismutase (Mn-SOD), and the relationship between SODs and other proteins localized in rimmed vacuoles in muscle biopsy specimens from three cases of sporadic IBM and two of distal myopathy with rimmed vacuoles (DMRV) as well as eight control cases of myopathies without rimmed vacuoles. Immunoblot analysis showed distinct protein bands of both SODs in IBM and DMRV using subtype-specific antibodies. Intensities of immunoreactive bands for Mn-SOD in IBM and DMRV were stronger than those in the control cases. Immunohistochemistry disclosed accumulation of both SODs in vacuolated muscle fibers in all cases of IBM and DMRV. Immunoreactivity for Mn-SOD was often colocalized with that of nitrotyrosine, cytochrome oxidase, tau, and lysosome-associated membrane proteins 2 (LAMP-2) in vacuolated fibers. Some of the Cu, Zn-SOD-positive vacuolated fibers were associated with ubiquitin. The two SODs may have different roles for cell protection, and the expression of Mn-SOD is associated with nitric oxide-induced oxidative damage in myopathies with rimmed vacuoles.     

A network system of medical and welfare information service for the patients,their families,hospitals, local governments,and commercial companies in a medical service area

A service information system using the Internet, which connected the various people who are related to medical treatment and nursing welfare, was constructed. An intractable neurological disease patient who lives in the Onga district, Fukuoka, Japan, and the people who are related to the service were chosen as test users in an experimental model. The communicated service information was divided into open-use data (electronic bulletin board, welfare service, medical care service, and link to private company service home page) and closed-use data (the individual patient's hysterics). The open data server was installed in an Internet service provider The open data could be accessed not only by the patient, but also by the family, information center, companies, hospitals, and nursing commodity store related to patient's nursing and medical treatment. Closed data server was installed in an information center (public health center). Only patient and information center staff can access the closed data. Patients should search and collect the service information of various medical and welfare services by themselves. Therefore, services prepared for the patient are difficult to know, and they cannot be sufficiently utilized. With the use of this information system, all usable service information became accessible, and patients could easily use it. The electronic bulletin board system (BBS) was used by patients for knowing each other or each others' family, and was used as a device for exchange of wisdom. Also, the questions for the specialist, such as doctor, dentist, teacher, physical therapist, care manager, welfare office staff member, and public health nurse, and the answers were shown on the BBS. By arranging data file, a reference of various patients in question and answer, which appeared in this BBS, was made as "advisory hints" and was added to the open data. The advisory hints became the new service information for the patients and their family. This BBS discovered the possibility of becoming an important information source for companies, hospital and, administration to know the requirements of patients and their families and the kind of services to be served. Although suppliers provide medical and welfare services for the patient, there is a tendency that the service information is sent by the suppliers at their own convenience. The information system in which various people participated was constructed in order to collect information for the patient, taking a patient-oriented approach. The result of the model test showed that this information system using Internet technology is a good system for both the service supplier and its receiver.