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Biomedical subjects

T Fukuhara

Publications and source records attributed to T Fukuhara.

At least 19 recordsLinked to original sources

Analysis of donor-type chimerism in lineage-specific cell populations after allogeneic myeloablative and non-myeloablative stem cell transplantation.

We analyzed donor-type chimerism in CD3+, CD14.15+ and CD56+ cells from 36 patients who had undergone conventional-intensity allogeneic stem cell transplantation (CST) and 34 patients who had undergone non-myeloablative allogeneic stem cell transplantation (NST) for hematological malignancies. On day 28 after transplantation, all fractions in NST patients and CD3+ cells in CST patients who received a non-total body irradiation (TBI) regimen showed more frequent mixed chimerism (<90% donor cells) than those in patients who had received TBI. NST patients with acute graft-versus-host disease (grade II-IV) frequently showed more than 50% donor-type chimerism in CD3+ cells on day 14 (P=0.029). NST patients with <50% donor-type chimerism on day 14 and with <90% donor-type chimerism on day 28 in CD56+ cells had significantly poor 1-year overall survival (0 vs 91%, P<0.001 and 20 vs 74%, P=0.002, respectively). Both NST and CST patients with <90% donor-type chimerism in CD14.15+ cells on day 28 had significantly poor 1-year overall survival (14 vs 70%, P=0.005 and 0 vs 66%, P=0.002, respectively). Our data show that the extent of donor-type chimerism in lineage-specific cells appears to have an impact on outcome after allogeneic stem cell transplantation.

Adolescent↗

Successful treatment with allogeneic peripheral blood stem cell transplantation and granulocyte transfusion for severe aplastic anemia with sinusitis.

A 43-year-old woman with severe aplastic anemia (SAA) received anti-thymocyte globulin and cyclosporin A (CyA) and achieved hematological remission. Although she had maintained hematological remission, the disease relapsed 10 months after arbitrary discontinuance of maintenance therapy with CyA. Resumption of CyA therapy was not effective, and her condition became complicated with progressive sinusitis with bone destruction, which was refractory to antibiotics, antifungal agents, granulocyte colony-stimulating factor, and surgical drainage. Because of the necessity for early neutrophil recovery (to resolve the infection), we proceeded with a combination therapy using allogeneic peripheral blood stem cell transplantation (PBSCT) promptly followed by granulocyte transfusion (GTX) from the same human leukocyte antigen-identical donor rather than carrying out a second immunosuppressive therapy. The patient showed temporal resolution of infection on the second day after a single GTX. Although the patient had pneumonia on day 11, it was resolved promptly after engraftment on day 16. This report suggests the clinical utility of a salvage therapy with allogeneic PBSCT followed by GTX in a particular case of recurrent SAA with refractory infections.

Adult↗

The wide distribution of endornaviruses, large double-stranded RNA replicons with plasmid-like properties.

The International Committee on Taxonomy of Viruses (ICTV) recently accepted Endornavirus as a new genus of plant dsRNA virus. We have determined the partial nucleotide sequences of the RNA-dependent RNA polymerase regions from the large dsRNAs (about 14 kbp) isolated from barley (Hordeum vulgare), kidney bean (Phaseolus vulgaris), melon (Cucumis melo), bottle gourd (Lagenaria siceraria), Malabar spinach (Basella alba), seagrass (Zostera marina), and the fungus Helicobasidium mompa. Phylogenetic analyses of these seven dsRNAs indicate that these dsRNAs are new members of the genus Endornavirus that are widely distributed over the plant and fungal kingdoms.

Basidiomycota↗

A nationwide survey of deep fungal infections and fungal prophylaxis after hematopoietic stem cell transplantation in Japan.

We conducted a nationwide survey to define incidence of deep fungal infections and fungal prophylaxis practices after HSCT. In all, 63 institutions responded. Total number of in-patient transplantations was 935: 367 autologous, 414 allogeneic myeloablative, and 154 allogeneic reduced-intensity (RIST) (n=154). Number of patients who were cared for in a clean room at transplant was 261 (71%) in autologous, 409 (99%) in conventional and 93 (66%) in RIST, respectively. All patients received prophylactic antifungal agents; 89% fluconazole. Number of patients who received the dosage recommended in the CDC guidelines (400 mg/day) was 135 (42%) in conventional transplant and 34 (30%) in RIST (P=0.037). Number of patients who received fluconazole until engraftment and beyond day 75 in conventional transplant vs RIST was, respectively, 324 (100%) vs 109 (97%), and 39 (12%) vs 18 (16%), with no significant difference between the two groups. A total of 37 patients (4.0%) were diagnosed with deep fungal infections; autologous transplantation (0.03%), conventional transplantation (6.0%) and RIST (7.1%). Wide variations in antifungal prophylaxis practice according to the type of transplant and the institutions, and deep fungal infection remain significant problems in RIST.

Antifungal Agents↗

Extended versus local fluctuations in quantum critical Ce(Ru1-xFex)2Ge2 (x=xc=0.76).

We present inelastic neutron scattering experiments, performed near the antiferromagnetic quantum critical point in Ce(Ru0.24Fe0.76)2Ge2. Both local and long-range fluctuations of the local moments are observed, but due to the Kondo effect only the latter are critical. We propose a phenomenological expression which fits the energy E, temperature T, and wave vector q dependences of the dynamic susceptibility, describing the non-Fermi liquid E/T scaling found at every q.

Journal Article↗

Temporal changes in liver cancer incidence rates in Japan: accounting for death certificate inaccuracies and improving diagnostic techniques.

Primary liver cancer (PLC) rates have risen dramatically during the past few decades in some regions, particularly in Japan, where PLC is now the third major cause of cancer death. PLC is one of the most difficult tumors to diagnose correctly, because (i) the liver is a frequent site of cancer metastasis and (ii) death from PLC is often attributed to cirrhosis or chronic hepatitis. Also, because the disease is often rapidly fatal, a large proportion of liver cancer cases are identified based on death certificates alone without confirmation by clinical records. Thus, worldwide differences in published incidence rates for this disease reflect regional or national differences in both the accuracy of death certificates and the sensitivity of diagnostic methods. By comparing death certificate causes of death with those based on pathology review, we were able to adjust 1958--1994 incidence rates for a large Japanese cohort for these errors. Although the death certificate false-positive error rate declined, the false-negative error rate remained high throughout the study. The introduction of improved liver cancer diagnostic methods in Japan in the early 1980s was associated with a sharp increase in PLC incidence. We conclude that errors in death certificate causes of death and changes in liver cancer diagnostic techniques have had an important impact on the reported incidence of this disease. Taking these factors into account, rates of hepatocellular carcinoma rose between 2.4- and 4.3-fold in our Japanese cohort from 1960 to 1985, peaked about 1993 and declined thereafter. Incidence rates of cholangiocarcinoma remained stable through 1987.

Carcinoma, Hepatocellular↗

Clinical features of late-onset idiopathic aqueductal stenosis.

BACKGROUND: Although late-onset idiopathic aqueductal stenosis (LIAS) is considered a good indication for endoscopic third ventriculostomy (ETV), the characteristics of this clinical entity have seldom been reported in the magnetic resonance (MR) imaging era. The authors reviewed their patients with LIAS who were treated by ETV to confirm its clinical features and response to treatment. METHODS: The study group was composed of 31 patients diagnosed with LIAS who were previously untreated. Both anatomic and cine phase-contrast MR studies were used to detect the obstruction of the aqueduct canal. The preoperative symptoms were statistically analyzed in relation to the age of the patients and the degree of preoperative ventriculomegaly. RESULTS: The overall success rate of ETV was 83.9% with mean follow-up duration of 26.2 months. Only two patients had acute onset (within one month) without any predisposing chronic symptoms. The patients with chronic symptoms (longer than 6 months [n = 25]) can be divided into two major groups: a headache group (n = 12) and a normal pressure hydrocephalus (NPH)-symptom group (n = 11), Two patients had both headaches and NPH symptoms. The patients in the headache group were significantly younger and had smaller ventricles than the patients in the NPH group. With multivariate regression analysis, age independently affected the type of chronic symptoms. CONCLUSIONS: LIAS typically presents with chronic onset, with younger patients tending to have headaches, and older patients tending to have NPH symptoms. ETV is considered the best surgical option, with more than an 80% success rate.

Adolescent↗

Immunohistochemical study of Ki-67 (MIB-1), p53 protein, p21WAF1, and p27KIP1 expression in benign, atypical, and anaplastic meningiomas.

Histologic grading of meningiomas has prognostic and clinical therapeutic implications. Meningiomas were histologically classified into 3 different World Health Organization grades. Grade II, an atypical meningioma, was defined by major and various minor histologic criteria. However, these histologic criteria sometimes are not fulfilled, and other criteria are necessary. We studied and analyzed the immunohistochemical expression of MIB-1, p53, p21WAF1, p27KIP1 proteins in 146 cases of meningiomas, including 109 benign, 27 atypical, and 10 anaplastic meningiomas. Most of the benign meningiomas expressed low MIB-1 labeling index (mean, 1.5%), and fewer cases had p53 protein expression. In contrast, the anaplastic meningiomas had a high labeling index of MIB-1 (mean, 19.5%) and always expressed p53 protein, with a mean labeling index of 6.3%. The atypical meningiomas had MIB-1 and p53 labeling indexes in the range between benign and anaplastic meningiomas, with mean labeling indexes of 8.1% and 3.5%, respectively. These expressions were statistically significant among benign, atypical, and anaplastic meningiomas (P <.001). We conclude that the immunohistochemistry of MIB-1 and p53 protein will be valuable in discriminating atypical meningiomas from benign or anaplastic meningiomas, at least in histologically borderline cases. In addition, we also found direct correlation of p21 and inverse correlation of p27 expressions in meningiomas with increasing histologic grade and proliferative index.

Aged↗

RNA-dependent RNA polymerase activity associated with endogenous double-stranded RNA in rice.

RNA-dependent RNA polymerase (RdRp) activity was detected in the crude microsomal fraction of rice cultured cells that contain a 14 kbp double-stranded RNA (dsRNA). RdRp activity is maximal in the presence of all four nucleotide triphosphates and Mg2+ ion and is resistant to inhibitors of DNA-dependent RNA polymerases (actinomycin D and alpha-amanitin). RdRp activity increases approximately 2.5-fold in the presence of 0.5% deoxycholate. Treatment of purified microsomal fraction with proteinase K plus deoxycholate suggests that the RdRp enzyme complex with its own 14 kb RNA template is located in vesicles. The RdRp enzyme complex was solubilized with Nonidet P-40 and purified by glycerol gradient centrifugation, then exogenous RNA templates were added. Results indicate that exogenous dsRNA reduces RNA synthesis from the endogenous 14 kb RNA template.

Cells, Cultured↗

Liver cancer in atomic-bomb survivors: histological characteristics and relationships to radiation and hepatitis B and C viruses.

Histological features of primary liver cancer among atomic-bomb survivors and their relationship to hepatitis B (HBV) and C viral (HCV) infections are of special interest because of the increased risk of liver cancer in persons exposed to ionizing radiation and the high and increasing liver cancer rates in Japan and elsewhere. We conducted a pathology review of liver cancers occurring from 1958 to 1987 among subjects in the 120,321 member cohort of 1945 Hiroshima and Nagasaki residents. A panel of pathologists classified tumor histological types and defined accompanying cirrhotic changes of the liver. Archival tissue samples were assessed for HBV using pathology stains and PCR. Reverse transcriptase (RT) PCR was used to determine HCV status. We used unconditional logistic regression to compare 302 hepatocellular carcinoma (HCC) cases to 53 cholangiocarcinoma (CC) cases, adjusting for age, year of diagnosis, sex and viral status. Cirrhotic changes occurred significantly more often among HCC than CC cases (76% in HCC and 6% in CC). Compared to CC cases, HCC cases were 10.9 times more likely to be HBV-positive (95% confidence interval: 2.1-83.2) and 4.3 times more likely to be HCV-positive (95% confidence interval: 1.1-20.5). No significant differences were found between HCC and CC cases in radiation exposures. The predominance of HCC in the atomic-bomb survivors follows the background liver cancer pattern in Japan. Our findings suggest that HBV and HCV are involved in the pathogenesis of HCC with or without cirrhosis and are significantly less important in that of CC.

Aged↗

Functional magnetic resonance imaging before and after ventriculoperitoneal shunting for hydrocephalus--case report.

A 70-year-old man with hydrocephalus was examined with functional magnetic resonance (fMR) imaging before and after ventriculoperitoneal shunting. Preoperatively, activation by right hand exercise revealed only a slight signal increase in the peri-rolandic area. However, 3 months after ventriculoperitoneal shunting, a significant signal increase was observed. fMR imaging may detect activity-related improvement of cerebral blood flow responses in patients with hydrocephalus after surgical treatment.

Aged↗

Effects of ventriculoperitoneal shunt removal on cerebral oxygenation and brain compliance in chronic obstructive hydrocephalus.

OBJECT: The pathophysiology of shunt malfunction has not been fully examined, probably because of the paucity of appropriate animal models. Using a canine model of chronic obstructive hydrocephalus, the effects of shunt placement and removal on physiological parameters were evaluated. METHODS: Fifteen dogs, nine in which chronic hydrocephalus was induced and six controls, were used in the experiment. Thirteen weeks after the induction of hydrocephalus, intracranial pressure (ICP), tissue and cerebrospinal fluid O2 saturation, response to hyperventilation, and brain compliance at low (5-15 mm Hg) and high (15-25 mm Hg) pressures were measured (untreated stage). Following this procedure, ventriculoperitoneal shunts were implanted in the dogs suffering from hydrocephalus. Two weeks later, the same series of measurements were repeated (shunted stage), following which the shunt systems were removed. One week after shunt removal, the last measurements were obtained (shunt-removed stage). All dogs underwent magnetic resonance imaging four times: before induction of hydrocephalus and before each measurement. All dogs with hydrocephalus also had ventriculomegaly (1.42 +/- 0.89 ml before induction of hydrocephalus compared with 3.4 +/- 1.64 ml 13 weeks after induction, p = 0.0064). In dogs in the untreated hydrocephalus stage, ICP remained within the normal range (8.33 +/- 2.60 mm Hg)--although it was significantly higher than that in the control group (5 +/- 1.41 mm Hg, p = 0.014). Tissue O2 saturation in the dogs in the hydrocephalus group (26.1 +/- 5.33 mm Hg) was lower than that in the dogs in the control group (48.7 +/- 4.27 mm Hg, p < 0.0001). After the dogs underwent shunt placement, significant improvement was observed in their ICP (5.22 +/- 2.17 mm Hg, p = 0.012) and tissue O2 saturation (35.2 +/- 6.80 mm Hg, p = 0.0084). However, removal of the shunt reversed these improvements back to the preshunt status. Hyperventilation induced significant decreases in ICP and O2 saturation at every measurement time and induced a significant decrease in tissue O2 saturation during the shunted stage, but not during the untreated and shunt-removed stages. Brain compliance measured at high pressure demonstrated a significant gradual decrease at every measurement. CONCLUSIONS: In chronic obstructive hydrocephalus, shunt placement improves ICP and cerebral oxygenation as well as the response to hyperventilation in the tissue. Shunt removal reverses these improvements back to levels present during the untreated stage. The decrease in brain compliance may be one of the factors responsible for symptoms in shunt malfunction.

Animals↗

Characteristics of Cyclodextrin Adsorption onto Activated Carbons.

Whereas the amount of cyclodextrin (CD) adsorbed onto the large-pore activated carbon A (AC-A) increased with the number of glucose units, the amount adsorbed onto the small-pore activated carbon B (AC-B) showed the opposite tendency. This behavior can be accounted for in terms of a molecular exclusion. It is known that a good linear relationship is obtained between the Freundlich constants log K and 1/N for hydrophobic adsorption. The adsorption of CDs onto AC-A obeyed this relation, but, because of the molecular exclusion, the plots of AC-B deviated greatly. The adsorption of CDs onto AC-A was not explainable in terms of solubility. This could be because, in the case of a solid compound, adsorbability depends on the chemical potential of the molecule in aqueous solution whereas solubility depends also on the heat of fusion of the solid. In order to estimate the relative chemical potential of CDs in water, a method based on the numbers of carbon atoms and oxygen atoms in the molecule was devised which allowed a more accurate estimation of CD adsorbability than did solubility. The mean pore diameter of AC-A increased after CD adsorption, while that of AC-B showed little change. Copyright 2000 Academic Press.

Journal Article↗

Nerve rootlets to be sectioned for spasticity resolution in selective dorsal rhizotomy.

BACKGROUND: The goal of this study is to confirm the efficacy of the protocol for selective dorsal rhizotomy (SDR). In this protocol, rootlets to be sectioned are selected by palpable responses elicited by intraoperative electrical stimulation, without detailed electromyographic classifications. METHODS: Thirty-six children with spasticity due to cerebral palsy underwent SDR according to our protocol. Priority was given to sectioning rootlets that showed palpable clonic or bilateral responses, which were considered abnormal, over sectioning rootlets that merely had hyperactive responses to intraoperative stimulation. The results of intraoperative monitoring and sectioning amount were analyzed by physical evaluation. RESULTS: Significant improvements were obtained in passive range of motion and muscle tone of the lower extremities. The total percentages of rootlets with abnormal and hyperactive responses at L3 and S1 were bilaterally correlated with preoperative spasticity of the hip adductors and the plantar flexors, respectively. When rootlets with hyperactive responses were excluded from the correlation analysis, no bilateral correlation was observed. From the correlation analyses between the improvement in the physical evaluation and the amount of nerve sectioned, it was concluded that a greater improvement in muscle tone in all examined muscles, except the hamstrings, could be obtained if larger amounts of nerve roots were sectioned. CONCLUSION: The number of rootlets with palpable abnormal and hyperactive responses elicited by intraoperative stimulation reflects the preoperative spasticity of multiple muscles. This implies that only selecting rootlets with palpable responses can be reliable. Because more sectioning leads to better spasticity resolution, our protocol should be reviewed to increase the percentage of rootlets sectioned with hyperactive responses, especially for innervated levels of severely affected muscles.

Adolescent↗

Risk factors for failure of endoscopic third ventriculostomy for obstructive hydrocephalus.

OBJECTIVE: This is a retrospective study to identify risk factors for failure in the treatment of obstructive hydrocephalus with endoscopic third ventriculostomy (ETV). METHODS: The records for 89 patients, including 32 with ventriculoperitoneal or ventriculoatrial shunt malfunctions or infections, who underwent ETVs between 1993 and 1998, at our institution, were examined. Multiple variables possibly related to failure were considered. These included age, sex, cause of hydrocephalus, presence and function of ventriculoperitoneal/ventriculoatrial shunts, history of shunt revisions or infections, symptoms, preoperative imaging results, presence of retained shunt catheters, postoperative meningitis, and postoperative ventricular size. RESULTS: Twenty-nine patients (32.6%) required subsequent shunt replacement and/or ETV revision. Of these 29 reoperations, 12 procedures (41.4%) were performed within 2 weeks and only 3 were performed more than 10 months after the initial ETV procedure. The ventricular size remained unchanged in 75% of the cases on the day after ETV, in 57.4% at 3 months, in 48.2% at 6 months, and in 41.8% at 1 year. Cine phase-contrast magnetic resonance imaging findings were consistent with postoperative symptomatic resolution in 96.3% of the cases. Seven patients (7.9%) experienced complications related to ETV, all of which were transient. Significant risk factors in univariate analyses were as follows: presence of Chiari Type I malformation (P = 0.003), shunt infection at presentation (P = 0.014), history of shunt infections (P = 0.0004), three or more previous shunt revisions (P = 0.0018), and postoperative meningitis (P = 0.0001). Late-onset idiopathic aqueductal stenosis was a significant predictor of good outcomes (P = 0.044). These factors were reanalyzed in a multivariate analysis, which confirmed a history of shunt infections and postoperative meningitis as independent risk factors. CONCLUSION: The risk of failure increases with intracerebral infection, likely because of obliteration of cerebrospinal fluid pathways.

Adolescent↗

Phylogenetic analysis of some large double-stranded RNA replicons from plants suggests they evolved from a defective single-stranded RNA virus.

Sequences were recently obtained from four double-stranded (ds) RNAs from different plant species. These dsRNAs are not associated with particles and as they appeared not to be horizontally transmitted, they were thought to be a kind of RNA plasmid. Here we report that the RNA-dependent RNA polymerase (RdRp) and helicase domains encoded by these dsRNAs are related to those of viruses of the alpha-like virus supergroup. Recent work on the RdRp sequences of alpha-like viruses raised doubts about their relatedness, but our analyses confirm that almost all the viruses previously assigned to the supergroup are related. Alpha-like viruses have single-stranded (ss) RNA genomes and produce particles, and they are much more diverse than the dsRNAs. This difference in diversity suggests the ssRNA alpha-like virus form is older, and we speculate that the transformation to a dsRNA form began when an ancestral ssRNA virus lost its virion protein gene. The phylogeny of the dsRNAs indicates this transformation was not recent and features of the dsRNA genome structure and translation strategy suggest it is now irreversible. Our analyses also show some dsRNAs from distantly related plants are closely related, indicating they have not strictly co-speciated with their hosts. In view of the affinities of the dsRNAs, we believe they should be classified as viruses and we suggest they be recognized as members of a new virus genus (Endornavirus) and family (Endoviridae).

Defective Viruses↗

Critical shunt-induced subdural hematoma treated with combined pressure-programmable valve implantation and endoscopic third ventriculostomy.

The authors present 2 patients with VP shunt-induced subdural hematomas (SDH) treated with pressure-programmable valve implantation and endoscopic third ventriculostomies (TV). The first patient is an 11-year-old girl who developed a shunt-induced SDH. Revision of the shunt valve with a higher-pressure valve resulted in a prolonged deterioration of her consciousness. External ventricular drainage at low pressure led to clinical improvement. A pressure-programmable valve set at 50 mm H(2)O was implanted, and the pressure gradually increased. At a pressure of 120 mm H(2)O symptoms recurred, even though the subdural collection was beginning to decrease in size. An endoscopic TV was performed, and the valve pressure was then increased to 200 mm H(2)O without any neurological symptoms. The second patient, a 7-year-old boy with shunt-induced SDH, had recurrent SDH, even after shunt revision with placement of a higher-pressure valve, which resulted in prolonged lethargy. A pressure-programmable valve was implanted with concurrent endoscopic TV. Gradual valve pressure increases up to 200 mm H(2)O could be performed without recurrent symptoms. Eventually, the shunt system was ligated to resolve residual positional headache, and the TV has been patent for more than 3 years. In both patients, the pressure-programmable valve was useful, since the optimal CSF drainage pressure changed during the period of recovery from symptomatic subdural collections. Concurrent TV appeared to enable increasing the valve pressure gradually without any neurological symptoms. The advantages of this combined approach are discussed.

Brain↗

The expression of a Vp1-like gene and seed dormancy in Mesembryanthemum crystallinum.

Seeds of the common ice plant (Mesembryanthemum crystallinum) germinate in distinct sub-populations over a time period of more than 4 weeks following imbibition. Distinguishing early (E)- and late (L)-germinating seeds is the expression of a homologue of the transcriptional activator VP1. The deduced amino acid sequence of ice plant VP1 (MVP1) is 39% identical (50% similar) to the sequence of the Arabidopsis VP1 homologue, ABI3. The amount of Mvp1 mRNA, transcribed from a single gene, is different in E and L seeds after water uptake. The levels of the Mvp1 transcripts are very low in immature and mature seeds and they increased during 6 days of imbibition. This expression profile of Mvp1 is different from known Vp1/ABI3-like genes in other plants. Cycloheximide (at 35 microM) abolishes the increase of Mvp1, and L seeds are turned into E seeds, which develop normally when the inhibitor is applied for a short time during imbibition. E seeds treated for the same time period are developmentally impaired and show no radicle elongation. We suggest that the presence and late disappearance of Mvp1 in L seeds is responsible for dormancy and after-ripening of late-germinating ice plant seeds.

Amino Acid Sequence↗