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Biomedical subjects

K Miyamura

Publications and source records attributed to K Miyamura.

At least 55 records · Page 3Linked to original sources

Epidemics of aseptic meningitis due to echovirus 30 in Japan. A report of the National Epidemiological Surveillance of Infectious Agents in Japan.

Two rages of epidemic of aseptic meningitis (AM) due to echovirus 30 (E30) in Japan were analyzed with respect to two sources of information, AM incidence and E30 isolation, both gathered through the National Epidemiological Surveillance of Infectious Diseases. The first E30 epidemic spread throughout Japan in 1983 and ceased within the year. The second epidemic, starting in 1989, continued for the three successive years, and in the last year, 1991, the total E30 reports numbered 4,061, the largest number of a single virus type ever reported. Although the epidemic showed temporal and geographical shift and lasted for one or two years in some areas, most laboratories reported the largest number of E30 isolation in 1991. Among E30-yielding cases with clinical information during 1982-1992, the associating frequency with AM was as high as 82.5%. Other central nervous system involvements such as encephalitis, myelitis, encephalomyelitis and/or paralysis were reported in 36 E30-yielding cases and their monthly and age distributions were different from those of AM cases. The proportion of such disease among E30-yielding cases (0.60%) was close to that of other enteroviruses (0.56%). During the epidemics, E30 was isolated more frequently from cerebrospinal fluid than was E4 or E9 which prevailed coincidentally. E30 was most frequently isolated from cases of 4-7 years of age, sharing the common characteristic pattern of age distribution with other enteroviral meningitis. E30-yielding cases, however, involved a large number of older age groups than those of other enterovirus infections, and this tendency was the most pronounced in the first epidemic year, 1983. The contribution of these E30 epidemics on the yearly trend of clinically reported AM incidence and on the shift of its age distribution was also analyzed.

Adolescent↗

Minimal residual disease after bone marrow transplantation for chronic myelogenous leukemia and implications for graft-versus-leukemia effect: a review of recent results.

Cure of leukemia by allogeneic BMT is achieved by the combined effect of the myeloablative preparative regimen and an allo-immune response of donor cells to residual leukemia termed the graft-versus-leukemia (GVL) effect. In the first year following BMT for CML, PCR used to detect the leukemia-specific BCR/ABL message frequently reveals subclinical levels of persisting leukemia. In a meta-analysis of reports on qualitative PCR findings after BMT for CML in 12 recently published series, we found that for unmanipulated BMT in chronic phase, PCR detection was not associated with a higher relapse risk and that most patients became PCR negative within 2 years post-BMT. In contrast, PCR detection of BCR/ABL transcripts was a more reliable predictor in recipients of T cell-depleted BMT and in those transplanted in accelerated or blastic phase of their disease. For accurate prediction of relapse, serial quantitative PCR is necessary. It could also be used to monitor efficacy of experimental treatments of relapse with interferon or donor lymphocyte transfusions. Furthermore, studies of the association of GVHD with PCR detection of BCR/ABL message may shed light on the relationship of GVL with minimal residual disease in CML.

Bone Marrow Transplantation↗

Long persistent bcr-abl positive transcript detected by polymerase chain reaction after marrow transplant for chronic myelogenous leukemia without clinical relapse: a study of 64 patients.

We report here the results of polymerase chain reaction (PCR) for bcr-abl transcript and clinical details derived from 64 chronic myelogenous leukemia (CML) patients after allogeneic bone marrow transplantation (BMT). A total of 139 samples (2 to 220 weeks after BMT) were analyzed and bcr-abl transcript was detected in 99 samples from 52 patients. Patients were defined as bcr-abl early negative (EN) if they had > or = 1 negative PCR result < or = 1 year post-BMT (n = 13), and bcr-abl late positive (LP) if they had > or = 1 positive PCR result > or = 1 year post-BMT (n = 21). Among LP patients, only two patients had hematologic/cytogenetic (clinical) relapse. Another 19 LP patients remained in clinical remission 7 to 130 weeks after positive analysis for bcr-abl transcript, including 5 patients who had persistent bcr-abl transcript detectable even 2 years after BMT. To estimate the relationship between clinical data and residual bcr-abl transcript, EN patients are compared with LP patients. However, no clinical data studied were significantly associated with the persistent PCR positivity. If only patients in chronic phase are compared, the t-test showed significant correlation between leukocyte count just before BMT and sustained bcr-abl transcript (P < .05). These results suggest that PCR positivity is frequently observed in CML patients who sustain clinical remission after BMT, without being predictive of imminent clinical relapse. Tumor burden at the time of BMT may play an important role in the latency of bcr-abl positivity after BMT.

Adolescent↗

Molecular epidemiology of a variant of coxsackievirus A24 in Taiwan: two epidemics caused by phylogenetically distinct viruses from 1985 to 1989.

In order to know the phylogenetic relationship and the route of transmission of a variant of coxsackievirus A24 (CA24v), an agent that caused four sequential outbreaks of acute hemorrhagic conjunctivitis from 1985 to 1989 in Taiwan, the nucleotide sequence variations in the virus-encoded proteinase 3C region (549 nucleotides) were studied with 19 isolates. The prototype strain (EH24/70), four isolates from Japan, and two isolates from Hong Kong were used for comparison. The nucleotide sequences of the Taiwan strains from the 1985-1986 and 1988-1989 epidemics were closely related within each epidemic, while they were more distantly related between strains from two epidemics. Phylogenetic analysis by the unweighted pairwise grouping method of the arithmetic average revealed that the 19 Taiwan isolates had diverged into two groups, 1985-1986 and 1988-1989 groups. The time at which these two groups diverged was estimated to be around May 1982, more than 3 years prior to the first appearance of the CA24v epidemic in Taiwan. On each occasion, the viruses caused a 2-year epidemic and then disappeared. The Taiwan isolates from 1985 to 1986 were closely related to the Japan isolates from 1985 to 1986 and the Taiwan isolates from 1988 to 1989 were phylogenetically close to the 1989 Japan isolates, indicating that Taiwan and Japan had two common-source outbreaks. However, none of the 1988 Taiwan isolates were phylogenetically close to the 1988 Japan or Hong Kong isolates. The evidence revealed that Taiwan has had two repeated but discontinuous introductions of CA24v since its first appearance in Taiwan in 1985. None of the other CA24v strains have been detected so far.

Base Sequence↗

Audiological study in guinea pigs with type I allergy induced in the inner ear.

Time course studies of electrocochleography and the auditory brain stem response were performed in guinea pigs that were passively sensitized by sera containing antidinitrophenyl reaginic antibody and specifically challenged by dinitrophenyl-bovine serum albumin injected through the stylomastoid foramen. A negative summating potential on electrocochleography was observed from 12 to 48 hours, but not at 72 hours, after the specific challenge. A threshold increase on the auditory brain stem response was observed 15 minutes after the specific challenge; the threshold recovered to the prechallenge level within 7 days. Further, we used Tranilast, a blocking agent of chemical mediator release from mast cells, before the specific challenge. A negative summating potential and head deviation were not observed after the use of this agent. These results suggest that the auditory change provoked in the inner ear of the sensitized guinea pig may have been induced by type I allergy.

Animals↗

Detection of minimal residual disease in Philadelphia chromosome positive acute lymphoblastic leukemia: rationale for bone marrow transplantation from the polymerase chain reaction point of view.

Bone marrow transplantation (BMT) is performed as curative therapy for acute lymphoblastic leukemia (ALL). In most patients, BMT is performed at the time of remission which implies that the number of leukemic cells is less than 5% of all hematopoietic cells, namely, 0 to 10(10) leukemia cells in the body. Thus, some patients may well undergo BMT despite the fact that no leukemic cells are left in the body. In this respect, more accurate diagnosis of complete remission status would be to the patients' benefit. To detect minimal residual disease (MRD) not found by light-microscopy, further strategies are required after achieving hematological remission. Cytogenetic methods, Southern blot analysis and conventional immunological techniques can all provide accurate diagnosis, however, the sensitivity of these techniques for the detection of MRD is just as low as that of the light microscopy. Recently, polymerase chain reaction (PCR) has become available for the detection of low levels of chimeric bcr-abl transcripts in Philadelphia chromosome positive (Ph1) ALL patients. With this assay, investigators have reported MRD in patients after chemotherapy or BMT. Most patients who achieve hematological remission after conventional chemotherapy still have bcr-abl transcript detectable by PCR, confirming the general concept that this particular leukemia needs BMT in order to cure the disease. Some patients who had MRD prior to BMT continued disease free survival > 1 year after BMT with a negative PCR result and in these patients, MRD seems to have been eradicated by the BMT procedure.(ABSTRACT TRUNCATED AT 250 WORDS)

Bone Marrow Transplantation↗

Autologous BMT in high risk patients with CALLA-positive ALL: possible efficacy of ex vivo marrow leukemia cell purging with monoclonal antibodies and complement.

Autologous BMT (auto-BMT) has been conducted for 17 high-risk common ALL antigen (CALLA)-positive non-T cell type ALL patients. Ex vivo purging of leukemia cells from infused BM cells was performed using complement and three kinds of mouse monoclonal antibodies reactive to CALLA-positive leukemia cells: NL-1 (IgG2a), NL-22 (IgM), and HL-47 (IgM). Minimal residual leukemia cells in BM were examined by PCR method in Philadelphia chromosome (Ph1)-positive ALL cases. BCR/ABL chimeric transcript, which was positive in BM samples before purging, was shown to be absent after ex vivo purging in all three cases tested. Among four Ph1-positive cases transplanted in first CR, three cases survived in CR remission 77, 29 and 26 months after BMT, and one case died without relapse 4 months after BMT. The other four Ph1-negative cases transplanted in the first CR also remained in CR except one who relapsed. The results of minimal residual leukemia cell studies and clinical data indicate the effectiveness of our ex vivo leukemia cell purging method and auto-BMT in the early stage of CR for patients with high risk ALL.

Adolescent↗

Unexpected heterogeneity of PML/RAR alpha fused mRNA detected by nested polymerase chain reaction in acute promyelocytic leukemia.

We have analyzed ten APL patients using reverse transcription polymerase chain reaction (RT-PCR) technique to detect PML/RAR alpha fused mRNA. All patients in this study had PML/RAR alpha fused mRNA (three cases of the short type and seven cases of the long type), although the chromosomal translocation t(15;17) was not detected in one patient. After ethidium bromide staining, two-thirds of the short type and all cases of the long type were found to have multiple PCR products (192 and 93 base pair (bp) bands in the short type and 666, 522, 263, and 164 bp in the long type). A total of six distinct fused mRNAs were sequenced (P1R1, P1R2, P3R1, P2R1, and P2R2). Southern hybridization analysis showed only one rearranged band in each of the patients. These results suggest that the longest mRNAs in each type are the authentic fused mRNAs and the other smaller mRNAs are generated through splicing events. In RAR alpha, a novel fusion point (R2) was identified within the fourth exon. This uncommon splicing may be caused by the instability of the splicing mechanism of the rearranged PML/RAR alpha gene. Among the ten APL patients, no correlation was observed between the type of fused mRNA and the clinical characteristics examined.

Adult↗

Detection of Philadelphia chromosome-positive acute lymphoblastic leukemia by polymerase chain reaction: possible eradication of minimal residual disease by marrow transplantation.

Minimal residual disease (MRD) in patients with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph1 ALL) who received allogeneic (n = 9) or autologous (n = 6) bone marrow transplantation (BMT) was evaluated by the polymerase chain reaction (PCR) for the bcr-abl transcript. Twelve patients received BMT at the time of hematologic and cytogenetic remission. However, MRD was detected in 8 of 10 patients evaluated. Seven patients, including three who had MRD before BMT, continue to have a disease-free survival 5 to 64 months after BMT. Twenty-one specimens obtained from these patients at various times after BMT did not show MRD. In three patients, MRD detected just before BMT seems to be eradicated by BMT protocol. The other eight patients developed cytogenetic or hematologic relapses 2 to 8 months after BMT. Seven of 14 samples from these patients demonstrated MRD, which preceded clinical relapse by 3 to 9 weeks. Thus, this technique for the detection of MRD appears to be useful for the more precise assessment of various antileukemia therapies and for early detection of leukemia recurrence.

Adolescent↗

Phylogenetically different strains of a variant of coxsackievirus A 24 were repeatedly introduced but discontinued circulating in Japan.

Variations in the nucleotide sequence of 3 C proteinase of coxsackievirus A 24 variant (CA 24 v) were analyzed to define the route of transmission and spread of the virus which was introduced to Japan on three separate occasions, 1985-86, 1988, and 1989. The nucleotide sequences of isolates from the same year's outbreak in Japan were identical or closely related, while the isolates from different outbreaks were less closely related to one another than to those from other countries in the same year. All Japanese isolates from Okinawa and other prefectures in 1985 and 1986 were closely related to the Taiwan strains in those same years, indicating common-source outbreaks. Two 1988 isolates from Chiba Prefecture, Japan, were closely related to those from Singapore in 1987, China in 1988 and Hong Kong in 1988. All seven Japanese isolates from Chiba Prefecture in 1989 comprised a group together with the Taiwan and Singapore strains in 1988. The results indicate that CA 24 v was introduced into Japan on each occasion from the outside. Furthermore, in contrast to the explosive epidemics in Okinawa Prefecture in 1985 and 1986, the virus which was repeatedly introduced to other areas in Japan did not circulate endemically, and disappeared within a short time.

Base Sequence↗

Phylogenetic analysis of a coxsackievirus A24 variant: the most recent worldwide pandemic was caused by progenies of a virus prevalent around 1981.

Nucleotide substitutions in the viral-encoded proteinase 3C (3Cpro) region (549 nucleotides) of the RNA genome of a coxsackievirus A24 variant (CA24v), one of the agents causing acute hemorrhagic conjunctivitis (AHC), were studied using 32 isolates collected from the Eastern hemisphere in 1970-1989. Based on regression analysis of nucleotide differences among isolates, the nucleotide substitution rate of CA24v 3Cpro was estimated to be 3.7 x 10(-3)/nucleotide/year. A phylogenetic tree constructed by the modified unweighted pair group method using arithmetic averages (UPGMA) indicated that CA24v had evolved from a common ancestor which appeared in one focal place in November 1963 +/- 21 months, about 7 years before the first isolation of CA24v in Singapore. The tree also revealed that all the recent epidemic isolates in 1985-1989 including Asian and Ghanian strains diverged from each other after 1981. This finding is consistent with the evidence that AHC due to CA24v had been confined to Southeast Asia and the Indian subcontinent until 1985, then suddenly and explosively spread to other areas where no CA24v isolations had been reported.

Amino Acid Sequence↗

Evaluation of enzyme immunoassay using a recombinant envelope protein expressed in insect cells for serological confirmation of HTLV-I infection.

A recombinant human T-lymphotropic virus type I (HTLV-I) envelope protein expressed in insect cells using a recombinant baculovirus was employed as the antigen in an enzyme immunoassay (renvEIA). Peripheral blood samples were obtained from asymptomatic carriers or healthy individuals. Plasma was tested for HTLV-I antibody by renvEIA, particle agglutination, and Western immunoblot (WB), and lymphocyte DNA was tested for HTLV-I proviral DNA amplification by polymerase chain reaction (PCR). Of 61 people aged 9 months or older, 23 were positive (gag+, env+) and 19 others were in the "indeterminate" category (gag+, env-) when their WB results were interpreted according to the WHO-proposed criteria. Thirty-seven cases, including all of the WB+ cases and 14 of 19 WB indeterminate cases, were positive by renvEIA. In 34 of 37 renvEIA-positive cases, the presence of long terminal repeat (LTR) and tax/rex region of HTLV-I proviral DNA was detected by polymerase chain reaction (PCR) and following Southern blot hybridization. Thus, renvEIA would be a useful supplemental assay to confirm the presence of HTLV-I antibody in HTLV-I asymptomatic carriers.

Adolescent↗

Type I allergy in the inner ear of the guinea pig.

Guinea pigs were passively sensitized by sera containing antidinitrophenyl reaginic antibody and specifically challenged by dinitrophenyl-bovine serum albumin injected through the stylomastoid foramen. Nystagmus, head deviation, negative summating potentials on electrocochleography, and an increase of threshold and wave I peak latency on auditory brain stem response testing were observed after local challenge. These physiologic changes were reversible and resolved within several days. We also used Tranilast before the specific challenge. It is a blocking agent of chemical mediator release from mast cells. Negative summating potentials and head deviation were not observed after the use of this agent. In the animals that showed physiologic changes, we observed endolymphatic hydrops, mast cell degranulation, and eosinophil infiltration histologically in the challenged side of the inner ear. These results suggest that the physiologic and histologic changes provoked in the inner ear of the sensitized animals may have been induced by type I allergy.

Animals↗

Enteroviral aseptic meningitis in Japan, 1981-1991. A report of the National Epidemiological Surveillance of Infectious Agents in Japan.

In Japan, aseptic meningitis cases due to enterovirus infections increase every summer in various degrees with an incidence peak usually in July. During the past 11 years from 1981 through 1991, a total of 8,595 enterovirus isolations from aseptic meningitis cases were reported from 54 participating laboratories. Eight enterovirus types caused large epidemics; more than 100 isolations of each type from aseptic meningitis cases were reported for every epidemic year of the respective type. They were coxsackievirus (C) types B3 and B5, echovirus (E) types 4, 6, 7, 9, 18 and 30. Among these, the highest meningitis-associating frequency was reported for E30, representing 82.6% of the total isolations reported for the type during this period, followed by E4, 71.1%. The frequencies of E9, E7, E6 and CB5 were in a range from 54.5% to 44.4%, while that of E18 was 37.7% and that of CB3 21.0%. During the epidemics, enterovirus-associated meningitis was most frequently reported among children of 4-7 years of age. High frequencies were also shown in infants less than 1-year of age in some types. A total of 4,240 enteroviruses were isolated from cerebrospinal fluid of aseptic meningitis cases, representing 49.3% of the cases with enterovirus isolation.

Adolescent↗

Poliovirus surveillance: isolation of polioviruses in Japan, 1980-1991. A report of the National Epidemiological Surveillance of Infectious Agents in Japan.

This report presents an overall distribution of poliovirus isolations in Japan, where poliomyelitis has been under control over two decades as a result of legal administration of two doses of the trivalent live oral poliovirus vaccine of the Sabin strains (OPV) to children under 48 months of age. During the past 12 years from 1980 through 1991, a total of 1,126 poliovirus isolations from humans and 268 isolations from sewage/river water were reported by respectively 49 and nine of the participating laboratories. Type 2 was most frequently isolated from children after administration of one dose of OPV, followed by type 1 and type 3. On the contrary, after the second dose of OPV, the rate of isolation of type 3 exceeded those of type 2 and type 1. Seasonal and age distribution of poliovirus isolations from both humans and sewage/river water paralleled the OPV vaccination schedule in Japan. One percent of the isolations were, however, from infants younger than the vaccination-scheduled ages and 5% were from children older than those ages, including one each from 15 and 16 years olds. The data indicate that the poliovirus has silently been disseminated from vaccinated children to others and the community, thus suggesting repeated transmission of the viruses. The fact that some elder children had poliovirus colonization in their alimentary tracts indicates a potential risk of infection of such a population when exposed to a wild virus and of becoming a source of transmission to others.

Adolescent↗

Bone marrow transplantation for chronic myelogenous leukemia in blastic phase using a phenotypically identical unrelated volunteer donor. Nagoya Bone Marrow Transplantation Group (NBMTG), Tokai Marrow Donor Bank (TMDB).

A 26-year-old male with chronic myelogenous leukemia in lymphoid blast crisis received a bone marrow transplant (BMT) from a phenotypically identical, mixed lymphocyte reaction (MLR)-weakly positive unrelated male volunteer donor. The volunteer was obtained from the Tokai Marrow Donor Bank (TMDB), which was established in Japan in 1989. This donor was selected from volunteer donors who were identical with our patient at the HLA-A,B loci, followed by matching at HLA-DQ, DR loci. On MLR testing, the donor's cells showed no response, but the patient's cells showed a low response to the donor's cells (relative response index 0.29). The patient showed rapid hemopoietic engraftment. He developed acute graft-versus-host disease (GVHD) with vesicle formation on palms and soles and mild liver damage, which were successfully treated with intravenous prednisolone 1 mg/kg per day. Although he also suffered from interstitial pneumonitis on day 64 and localized varicella-zoster infection on day 87, and has suffered from moderate stomatitis and dry skin characteristic of chronic GVHD, he is currently 22 months post-transplant with hematological remission and has a normal daily social life.

Adult↗