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Biomedical subjects

K Asami

Publications and source records attributed to K Asami.

At least 37 records · Page 2Linked to original sources

Effective control of Epstein-Barr virus-related hemophagocytic lymphohistiocytosis with immunochemotherapy. Histiocyte Society.

The familial form of hemophagocytic lymphohistiocytosis (HLH) is a lethal disorder. Although the prognosis for Epstein-Barr virus-associated HLH (EBV-HLH) remains uncertain, numerous reports indicate that it can also be fatal in a substantial proportion of cases. We therefore assessed the potential of immunochemotherapy with a core combination of steroids and etoposide to control EBV-HLH in 17 infants and children who met stringent diagnostic criteria for this reactive disorder of the mononuclear phagocyte system. Treatment of life-threatening emergencies was left to the discretion of participating investigators and typically included either intravenous Ig or cyclosporin A (CSA). Five patients (29%) entered complete remission during the induction phase (1 to 2 months), whereas 10 others (57%) required additional treatment to achieve this status. In 2 cases, immunochemotherapy was ineffective, prompting allogeneic bone marrow transplantation. Severe but reversible myelosuppression was a common finding; adverse late sequelae were limited to epileptic activity in one child and chronic EBV infection in 2 others. Fourteen of the 17 patients treated with immunochemotherapy have maintained their complete responses for 4+ to 39+ months (median, 15+ months), suggesting a low probability of disease recurrence. These results provide a new perspective on EBV-HLH, showing effective control (and perhaps cure) of the majority of EBV-HLH cases without bone marrow transplantation, using steroids and etoposide, with or without immunomodulatory agents.

Child↗

Improvement in CNS protective treatment in non-high-risk childhood acute lymphoblastic leukemia: report from the Japanese Children's Cancer and Leukemia Study Group.

BACKGROUND: Prevention of central nervous system (CNS) leukemia by early introduction of therapy to this sanctuary site is an essential component of modern treatment strategy for acute lymphoblastic leukemia (ALL). However, the optimal form of preventive CNS therapy remains debatable. PROCEDURE: To address this issue, we evaluated the efficacy of CNS preventive therapy for 572 children with ALL who achieved complete remission in the Children's Cancer and Leukemia Study Group (CCLSG) ALL874 (1987-1990) and ALL911 (1991-1993) studies. They received risk-directed therapy based on age and leukocyte count. In the ALL 874 study, the non-high-risk (low-risk [LR] + intermediate risk [IR]) patients were randomly assigned to the conventional cranial irradiation (CRT) regimen (L874A and I874A) and the high-dose methotrexate (HDMTX) regimen without CRT (L874B and I874B). The former patients received 18-Gy CRT plus 3 doses of intrathecal (i.t.) MTX and the latter patients received 3 courses of HDMTX at 2 g/m2 plus 13 doses of ITMTX (L874B) or 4 courses of HDMTX at 4.5 g/m2 plus 1 dose of ITMTX (I874B). RESULTS: The 7-year probabilities (+/- SE) of CNS relapse-free survival were 97.3% +/- 2.6% (L874A, n = 41) vs. 90.3% +/- 5.3% (L874B, n = 39) (P = 0.25) in the LR patients, and 100% (I874A, n = 55) vs. 78.5% +/- 6.5% (I874B, n = 54) (P = 0.002) in the IR patients. The corresponding disease-free survival (DFS) rates were 79.4% +/- 6.5% vs. 74.4% +/- 7.3% (P = 0.62) in the LR group and 63.3% +/- 6.8% vs. 58.3% +/- 7.2% (P = 0.66) in the IR group. Thus, the HDMTX regimen could not provide better protection of CNS relapse as compared with the CRT regimen, although their overall efficacy was not significantly different. In the ALL 911 study, intensive systemic chemotherapy with extended i,t, injections of MTX plus cytarabine achieved a high CNS relapse-free survival (98% +/- 1.9% at 7 years) and a favorable DFS (85.5% +/- 5% at 7 years) in the IR patients. The patients in the high-risk (HR) group in both ALL874 and ALL911 studies received the 18-Gy or 24-Gy CRT with intensive systemic chemotherapy. Their 7-year probabilities of CNS relapse-free survival ranged from 88% to 95%, among which the T-ALL patients had a risk of CNS leukemia, which was 3-4 times higher compared with B-precursor ALL patients. CONCLUSIONS: These results indicate that long-term intrathecal CNS prophylaxis as well as appropriate systemic therapy for the non-high-risk patients can provide protection against CNS relapse equivalent to that provided by cranial irradiation.

Adolescent↗

Malignant paraganglioma metachronously recurring at short duration in different paraganglions: report of a case.

We report the rare case of a 57-year-old man with retroperitoneal malignant paraganglioma. He was referred to our hospital complaining of left lower abdominal dull pain. Computer tomography (CT), magnetic resonance imaging, and aortography showed a mass measuring 5 x 4 cm in size on the left side of the abdominal aorta below the renal artery. The resected tumor was confirmed histologically to be malignant paraganglioma. Irradiation of the resected area was performed. Four months after the operation, an abdominal CT scan showed a 5.5 x 3.0 cm mass on the right side of the aorta below the diaphragm. This tumor was thereafter also resected. Three months after the second operation, a soft subcutaneous nodule measuring 4.5 x 2.0 cm in size was palpable above the left clavicle and was visible on a CT scan. A resection was again performed. All tumors showed the same histological findings. This is the first case reported in the Japanese literature with such a short-term demonstration of multiple metachronous recurrences in different paraganglions.

Humans↗

Pancreatic arteriovenous malformation observed to bleed from the bile duct and a duodenal ulcer: report of a case.

A 48-year-old man with recurrent episodes of biliary colic and subsequent pancreatitis was admitted to undergo a cholecystectomy. A gastroduodenal fiberscopic examination was performed because of massive melena on the seventh day after admission. It revealed a shallow ulcer on the posterior wall of a duodenal bulbus with rubor and an exposed vessel, which was clipped endoscopically to stop the bleeding. Further observations showed the papilla of Vater to be bleeding from the papilla. A contrast-enhanced abdominal computed tomography scan demonstrated a dilatation of the common bile duct and several dilated vasculatures around the portal vein, some of which drained into the portal vein. Based on the angiography findings, a diagnosis of arteriovenous malformation in the pancreas head was obtained and an embolization of the gastroduodenal artery was performed. Although the melena subsided, he underwent a pylorus-preserving pancreatoduodenectomy to prevent the recurrence of hemorrhaging. The histopathological findings of the bile duct revealed inflammatory cell infiltration and a detachment of the epithelium, except in a small part of the bile duct. A rupture of a damaged vessel inside the bile duct was observed, which was thought to be the cause of hemobilia. Sections of the pancreatic head demonstrated an inflammatory lesion with fibrosis and saponification as well as a large degree of arteriovenous anastomosis. The patient was discharged on the 35th day after the operation following an uneventful postoperative course.

Arteriovenous Malformations↗

Real-time monitoring of yeast cell division by dielectric spectroscopy.

To assay cell cycle progression in synchronized culture of yeast we have applied dielectric spectroscopy to its real-time monitoring. The dielectric monitoring is based on the electromagnetic induction method, regarded as a nonelectrode method, which has resolved the problems encountered in measurements with metal electrodes, namely electrode polarization and bubble formation on electrodes. In the synchronized culture with temperature-sensitive cell division cycle mutants, the permittivity of the culture broth showed cyclic changes at frequencies below 300 kHz. The increase and decrease in the cyclic changes of the relative permittivity correspond to the increase in cell length and bud size and to the septum formation between mother and daughter cells, respectively.

Biophysical Phenomena↗

Internal tandem duplication of the FLT3 gene and clinical evaluation in childhood acute myeloid leukemia. The Children's Cancer and Leukemia Study Group, Japan.

We analyzed tandem duplication in the juxtamembrane (JM) domain of the FLT3 (FMS-like tyrosine kinase 3/FLK2, CD135) gene in 94 children with acute myeloid leukemia (AML) and evaluated its correlation with clinical features. Longer polymerase chain reaction (PCR) products were observed in five patients; 1/3 of M0, 119 of M1, 1/39 of M2, 1/9 of M3 and 1/12 of M5. The sequence analyses of abnormal PCR products showed that all the abnormal products were derived from tandem duplications involving the JM domain and that all the lengthened sequences were in-frame as we previously reported. Statistical analyses revealed a significantly lower incidence of the tandem duplication in childhood AML patients than in adult patients (P < 0.05), and significantly shorter disease-free survival in patients with mutant FLT3 than in patients with wild-type FLT3 (P < 0.05). Our results suggest that the tandem duplication in the JM domain of the FLT3 gene is not a frequent phenomenon but might be a factor of poor prognosis in childhood patients with AML.

Acute Disease↗

Survey of 222Rn concentrations in the air of a tunnel located in Nagano City using the solid-state nuclear track detector method.

The survey of 222Rn concentration in the air of tunnels constructed during World War II has been performed using a solid-state nuclear track detector technique. For the practical application of this technique to the determination of 222Rn concentrations in air, some basic properties were experimentally examined on the cellulose nitrate film, Kodak LR 115 type II. The calibration coefficient of the cellulose nitrate film used is determined from a correlation between the 222Rn concentration in air and the observed number of perforated etched tracks for widespread radon concentrations. The slope of the linear relationship observed yields a calibration coefficient of (0.00209 +/- 0.00018) tracks cm(-2) (Bq m(-3) h)(-1). From the survey of 222Rn concentration in the air of tunnels, the concentration of several thousand Bq m(-3) was observed at the inner most area of the tunnel, and the seasonal variation was clearly observed. The exponential distribution of radon concentration as a function of distance from the openings of the tunnel suggests that the radon concentration in the tunnel is basically governed by diffusion and mixing of radon gas with air.

Air Pollutants, Radioactive↗

Effects of granisetron in children undergoing high-dose chemotherapy: a multi-institutional, cross-over study.

The efficacy of granisetron hydrochloride 20 microg/kg and 40 microg/kg were compared using a cross-over method to determine the optimal dose in children with solid tumors receiving high-dose chemotherapy. Granisetron controlled the onset of vomiting in 17 of 23 patients (73.9%) who were given 40 microg/kg of granisetron, while 8 of 21 patients (38.1%) were free of vomiting in the 20 microg/kg group. The average frequency of vomiting was 7.22 times in the 20 microg/kg dose versus 4.44 times in the 40 microg/kg dose. No safety problems were associated with either dose. The 40 microg/kg dose of granisetron appears to be more optimal.

Adolescent↗

11p15 translocations involving the NUP98 gene in childhood therapy-related acute myeloid leukemia/myelodysplastic syndrome.

In a survey of childhood therapy-related acute myeloid leukemia/myelodysplastic syndrome (t-AML/MDS) in Japan, we found 11p15 translocations in 5 (6%) of 81 children with t-AML/MDS. t(11;17)(p15;q21), t(11;12)(p15;q13), t(7;11)(p15;p15), inv(11)(p15q22), and add(11)(p15) were each found in one patient. Southern blotting and/or RT-PCR analyses revealed rearrangements of the NUP98 gene in tumor samples of all five patients. Rearrangements of DDX10 were detected in t-AML/MDS cells with inv(11), and rearrangements of HOXA9 were detected in t-AML cells with t(7;11). The 17q21 breakpoint of t(11;17) and the 12q13 breakpoint of t(11;12)(p15;q13) coincided with the loci of the HOXB and HOXC gene families, respectively. Therefore, it is reasonable to speculate that one of the HOXB genes and one of the HOXC genes were fused to NUP98 by t(11;17) and t(11;12), respectively, in t-AML/MDS cells. We propose that NUP98 may be a target gene for t-AML/MDS, and that t-AML/MDS with a fusion of NUP98 and HOX or DDX10 genes may be more frequent in children than in patients of other age groups.

Acute Disease↗

Expression of multidrug resistance-related genes does not contribute to risk factors in newly diagnosed childhood acute lymphoblastic leukemia.

BACKGROUND: The present study was designed to evaluate the association of multidrug resistance gene (MDR1), multidrug resistance-associated protein (MRP) gene and lung resistance protein (LRP) gene expression (mRNA levels) with risk factors such as phenotype, age and leukocyte count in newly diagnosed childhood acute lymphoblastic leukemia, because biological mechanisms contributing to risk factors were not known. METHODS: Expression of the MDR1, MRP and LRP genes in leukemic cells from 40 pediatric patients was quantitated using the reverse transcriptase polymerase chain reaction method. The associations of expression of these genes with age and leukocyte count, which are known as risk factors for acute lymphoblastic leukemia (ALL), were analyzed. Moreover, the associations with clinically classified risk-related groups (high-risk ALL and low-risk ALL) were also investigated. RESULTS: No positive correlations between expression of these genes and age or leukocyte count were found. The expression of these genes was not different among clinically classified risk-related groups. CONCLUSIONS: Expression (mRNA levels) of the MDR1, MRP and LRP genes did not contribute to risk factors in newly diagnosed childhood acute lymphoblastic leukemia.

Adolescent↗

[Troublesome factors in mitral valve repair for mitral valve regurgitation].

Limitations in the long-term results of medical treatment for mitral regurgitation are well recognized, but the advances in its surgical repair have produced good results. Therefore, early surgical intervention has been the focus of treatment in Europe and America. Increased surgical intervention depends on the development of technical skills in mitral reconstruction. This study investigated presurgical factors making surgical reconstruction difficult in 103 patients who underwent mitral operations performed from April 1994 to September 1997 in our hospital. Records were reviewed retrospectively for etiology, type of operation, and the immediate result of operation. The etiology of mitral regurgitation was prolapse in 65 patients (63%), restriction in 14, normal in 11, infectious endocarditis in 10, and others in 3. The type of prolapse involved the anterior leaflet in 22 patients (34%), posterior in 28 (43%), and both leaflets in 15 (23%). Valve repair was attempted in 74 patients, of which 16 were switched to valve replacement during operation. These included anterior leaflet prolapse in 9 patients, posterior leaflet in 1, both leaflets in 3, restriction in 2 and infectious endocarditis in 1. The success rate for reconstruction of anterior leaflet prolapse was not high. The cause of mitral regurgitation was mostly prolapse of the mitral valve, in our country as well as in Europe and America. Prolapsed posterior leaflet is much more common in Europe and America, and there is a high success rate reported for its valve reconstruction. In contrast, this study cannot recommend earlier surgical intervention because of difficult repair for anterior leaflet prolapse.

Female↗

Frequent aberration of FHIT gene expression in acute leukemias.

We analyzed the mRNA expression of the FHIT gene by reverse transcription-PCR (RT-PCR) in 54 cases of acute lymphoblastic leukemia (ALL; 11 cases of T-cell ALL [T-ALL] and 43 cases of non-T-ALL) and 40 cases of acute myeloid leukemia (AML). In 46% of the ALL cases and 55% of the AML cases, FHIT expression was absent or markedly decreased. Only abnormal short bands were detected in 30% of the ALL cases and 5% of the AML cases. Eighteen of 19 abnormal transcripts had the same fusion of exons 2-7, and all lacked the starting codon in exon 5. No obvious normal-sized PCR products were detected in cases exhibiting abnormal transcripts. These findings suggest that the expression of functional FHIT protein was lost in the majority of ALL (76%) and AML (60%) cases. Differential quantitative PCR of exons 3-9 of the FHIT gene and RT-PCR of the PTPRG gene, which is centromeric to the FHIT gene, showed the presence of the target sequences. Fluorescence in situ hybridization analysis using probes covering exons 5 and 8 revealed no difference in the signal patterns between leukemia and normal cells, showing one or two signal doublets in more than 90% of nuclei, and indicated that gross segments of the FHIT gene were not homozygously deleted in these cases. A small number of transcripts with an aberrant fusion between exons 2 and 7 were detected by RT-PCR in the bone marrow cells from four healthy individuals. Granulocytes, lymphocytes, and monocytes in the bone marrow cells of a healthy individual contained transcripts with the same fusion. This unique fusion of exons 2 and 7 might be preferentially seen in either neoplastic or normal hematopoietic cells, regardless of their lineage. The finding that FHIT expression was abolished in the majority of leukemia cases might support the hypothesis that the FHIT gene acts as a tumor suppressor, at least in leukemia.

Acid Anhydride Hydrolases↗

Dielectric behavior of budding yeast in cell separation.

Dielectric behavior of budding yeast in cell separation was studied by comparing two types of temperature-sensitive cell division cycle mutants that arrest before and after cell separation at the restrictive temperature. Single spherical cells before budding but after cell separation showed one main dielectric dispersion (centered at about 1 MHz) and one additional dielectric dispersion (at about 20 MHz), which were the Maxwell-Wagner dispersions due to the plasma membrane and due to both of the cell wall and vacuole, respectively. With cells that accumulated as doublets at a point immediately before cell separation, one more dielectric dispersion appeared around 200 kHz in addition to two dielectric dispersions similar to those found for the single cells without bud. The difference in dielectric behavior between the two types of cells might be mainly attributed to the difference in cell shape, which was theoretically examined using non-spherical cell models.

Cell Cycle↗

Repassivation of titanium and surface oxide film regenerated in simulated bioliquid.

The change in potential during repassivation of titanium in artificial bioliquids was examined, and the regenerated surface oxide film on titanium was characterized using X-ray photoelectron spectroscopy and Auger electron spectroscopy to elucidate the repassivation reaction of titanium in a biological system. The repassivation rate in Hanks' solution was slower than that in saline and was not influenced by the pH of the solution. This indicates that more titanium ions dissolve in a biological system than hitherto was predicted when the surface film is destroyed. Phosphate ions are taken up preferentially in the surface film during regeneration, and the film consists of titanium oxide and titanium oxyhydroxide containing titanium phosphate. Calcium ions and phosphate ions are adsorbed by the film after regeneration, and calcium phosphate or calcium titanium phosphate is formed at the outermost surface. Ions constituting Hanks' solution other than calcium and phosphate were absent from the surface oxide.

Biocompatible Materials↗

Mutational analysis of the N-ras gene in acute lymphoblastic leukemia: a study of 125 Japanese pediatric cases.

A point mutation of the N-ras gene is one of the known genetic alterations identified in patients with acute lymphoblastic leukemia (ALL), but its clinical importance is still controversial. Using polymerase chain reactions, we examined codons 12, 13 and 61 of this gene in 125 Japanese childhood ALL patients (64 common-ALL, 22 pre-B-ALL, 33 T-ALL, 2 B-ALL, 3 undifferentiated ALL, and 1 unclassified ALL) including 9 relapsed patients. An N-ras point mutation was observed in 14 (11%) patients (9 common-ALL, 3 T-ALL, and 2 undifferentiated ALL; 13 patients at diagnosis and 1 at relapse). The patients with undifferentiated ALL harbored an N-ras mutation at a significantly higher rate. However, no correlation was found between the presence of an N-ras mutation and sex, age, or white blood count. There was no significant difference in the event-free survival rate between 13 fresh patients with an N-ras mutation and 103 patients with a wild-type configuration. The N-ras mutation was present in about 10% of childhood ALL cases but it did not have a prognostic impact. The sequence analyses revealed that the majority of the patients (13/14) had an N-ras mutation of a G to A transition. This finding was consistent with previous reports on N-ras mutations in acute leukemias in which the incidence of a G to A mutation was significantly higher in ALL than in myeloid malignancies.

Child↗

Incidence of febrile convulsions in children with congenital hypothyroidism.

Brain excitability has been inconsistently reported to be increased both in hypo- and hyperthyroidism, but there have been few studies on the effects of thyroid hormones on brain excitability in children. With this in mind, we investigated the incidence of febrile convulsions (FCs) among patients with congenital hypothyroidism, who have been taking L-thyroxine since the age of 1 month. The incidence of FCs among congenital hypothyroid patients was 1.6% (1/63) which was significantly low (p < 0.05) compared with that of normal control children who visited our hospitals as outpatients (28/341, 8.2%) and that of others (322/3301, 9.8%) investigated 33 years ago in the same area. The incidence of FC among siblings of the 63 patients (7/74, 9.5%) was not statistically different from the controls. At least 8 of the 126 parents (6.4%) had experienced FC, however, only one child was affected in the 8 families. In conclusion, it seems likely that patients with congenital hypothyroidism on regular L-T4 replacement are less prone to experience FC. More studies on the incidence of convulsive disorders in children with thyroid diseases are needed to clarify the effects of thyroid hormones on brain excitability.

Adolescent↗

Atypical form of the fourth criterion for transient entrainment.

The typical fourth criterion for transient entrainment is defined when both a sudden shortening in conduction interval to and a distinct change in electrogram morphology at a bipolar recording site are demonstrated while performing overdrive pacing of a reentrant tachycardia from a single pacing site at two different constant rates. The purpose of this article was to test the hypothesis that if an intracardiac recording site showing both orthodromic and antidromic capture with entrainment pacing is located suitably distant from the circuit, sudden shortening in conduction interval to that site may occur without any significant change in the bipolar electrogram morphology (i.e., atypical form of the fourth criterion). Atrial overdrive pacing of orthodromic tachycardia was performed in 20 patients with either left anterior (12 patients) or left posterior (8 patients) accessory pathways. We investigated the effects of overdrive pacing from the proximal or distal coronary sinus, specifically effects on the electrogram interval and the electrogram morphology at the right atrial appendage. Overdrive pacing of orthodromic tachycardia from the proximal coronary sinus was performed in 10 of the 12 patients with left anterior accessory pathways; those 10 patients demonstrated the first entrainment criterion at the right atrial appendage site. Overdrive pacing of orthodromic tachycardia at still shorter cycle lengths demonstrated a sudden shortening in conduction interval to the right atrial appendage site. Despite shortening in conduction interval the morphology of the right atrial appendage electrogram was completely or almost identical to that during orthodromic tachycardia, indicating an atypical form of the fourth criterion. This criterion was not demonstrated in patients with left posterior accessory pathways. Thus, atypical fourth entrainment criterion was demonstrated during overdrive pacing of orthodromic tachycardia from the proximal coronary sinus only in patients with left anterior accessory pathways. Demonstration of atypical fourth criterion seems largely dependent on the location of the accessory pathway, the pacing, and the recording sites.

Adolescent↗