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Biomedical subjects

J Hara

Publications and source records attributed to J Hara.

At least 109 records · Page 6Linked to original sources

Developmental process of the T-cell receptor alpha and delta gene assembly in B-cell precursor acute lymphoblastic leukaemia.

We analysed the organization of V delta genes and delta recombining element (delta Rec) in 27 children with B-cell precursor acute lymphoblastic leukaemia. Twenty-two of 54 alleles showed rearrangements of the T-cell receptor (TCR) delta locus. These rearrangements resulted either from D2D delta 3 (2 alleles) or V delta 2(Dn)D delta 3 (20 alleles) recombinations, and the other V delta and delta Rec were not rearranged. Of 23 alleles with deletion of C delta and rearrangements of J alpha, V delta 2, V delta 4 and V delta 5 appeared to rearrange to J alpha on five alleles. With regard to the relationship between the rearranged V alpha/delta and J alpha genes, gene segments 5' to V delta 2 frequently rearranged to J alpha more proximal to C alpha, whereas V delta 2 and gene segments 3' to V delta 2 showed a tendency to rearrange to J alpha distal to C alpha. Based on these findings, we suggest that the initial recombination event of the TCR-alpha/delta gene may be D2D delta 3 joining, followed by V delta 2 recombination with the D2D delta 3 complex. It was also suggested that use of V alpha/delta and J alpha/delta may depend on the distance between the involved V alpha/delta and J alpha/delta at least in B-lineage cells. These rearrangements in B-precursor cells appear to be aberrant. However, this recombinational process may be one of the normal differentiation pathways in T-lineage cells, because cells with a V delta 2(Dn)D delta 3 rearrangement were detected in 0.1-0.01% of normal peripheral mononuclear cells by the polymerase chain reaction.

Base Sequence↗

In vivo and in vitro expression of myeloid antigens on B-lineage acute lymphoblastic leukemia cells.

The expression of myeloid antigens has been extensively examined using two-color analysis in 43 children with B-lineage acute lymphoblastic leukemia (ALL). On pre-culture cells, CD33 expression was frequently observed in CD19+, CD10- B-precursor ALL, and CD14 was expressed only on the cells from B-precursor ALL expressing CD19, CD10 and CD20, and B-ALL. After 2 or 3 days of culture without TPA, CD13 emerged on the cells from 21 of 29 patients irrespective of the presence or the absence of fetal calf serum in the culture. Of four patients with CD10+ B-precursor ALL, which showed no expression of CD13 after culture, two had T-cell associated antigens. Whereas the addition of TPA to the culture enhanced the expression of CD13 on the cells from acute non-lymphocytic leukemia (ANLL), TPA reduced the expression of this antigen on B-precursor cells. These findings suggest that the regulatory mechanism of CD13 expression may be different between B-precursor ALL and ANLL. Co-culture with cycloheximide mostly abrogated the induction of CD13, suggesting that CD13 expression was mainly dependent on de novo protein synthesis.

Adolescent↗

Induction of non-MHC-restricted cytotoxicity in a patient with pure red cell aplasia: functional relevance to antigen-specific cytotoxic T cells.

A functional analysis of an expanded T-cell subpopulation was studied in a patient with pure red cell aplasia who had no evidence of malignancy. In the time of an aggravation of the anemia, an expanded population of large granular lymphocytes (LGL) with T-cell receptor (TCR) alpha beta +CD3+CD8+ phenotype was noted, which reverted to normal with remission. These T cells displayed a polyclonal pattern in DNA analysis. Functionally, the T cells, with suppressor/cytotoxic phenotype exhibited normal capabilities for transducing the signals of the proliferative response, and of interleukin-2R (IL-2R) expression and IL-2 production via the TCR-CD3 complex structure. While they suppressed erythroid colony formation in vitro, neither non-major histocompatibility complex-restricted cytotoxic activity, cytotoxic T-cell activity, nor suppressive activity for immunoglobulin synthesis by B cells was detected. Pretreatment by anti-CD3 or anti-T-cell receptor antibody generated cytotoxicity for FcR+ target cells in the patient cells, but no such augmentation was found with other monoclonal antibodies of FcR- target cells. These findings indicated that the expanded T cells are functionally relevant to antigen-specific cytotoxic T lymphocytes.

Adult↗

Increased expression of the multidrug-resistance gene in undifferentiated sarcoma.

We analyzed multidrug-resistance gene (mdr1 gene) expression in a patient with undifferentiated sarcoma of the liver using the cloned cDNA for the mdr1 gene. Tissue samples were available at the time of initial diagnosis and of two intracranial relapses after chemotherapy with a regimen including doxorubicin and teniposide. The level of mdr1 gene expression was increased sevenfold in the intracranial tumor at the time of first relapse and 11-fold at the second relapse. This case may be an example of acquired multidrug resistance associated with overexpression of the mdr1 gene.

Child, Preschool↗

Alteration of N-ras gene mutation after relapse in acute lymphoblastic leukemia.

We investigated N-ras activation in childhood acute lymphoblastic leukemia (dALL) by the polymerase chain reaction (PCR) and the oligonucleotide hybridization method. The frequency of point-mutation of the N-ras gene was not high (2 of 15), and one positive case who relapsed was analyzed in detail. Although N-ras gene activation was detected at both onset and relapse, the mutation sites were different. At onset, Gly (GGT) was changed to Ser (AGT) at codon 12, and at relapse, Gly (GGT) to Asp (GAT) was observed at the same codon. In addition, the DNA at relapse showed a remarkably higher transforming activity than the DNA at onset on two independent recipient cell lines. The identical cell surface phenotype and the same rearrangement patterns of both the immunoglobulin (Ig) heavy chain and T-cell receptor (TCR) gamma chain genes indicated that the leukemic cells at onset and those at relapse were derived from the same precursor cell. Therefore, this case supports the concept that ras activation is not the event initiating leukemogenesis, but may be involved in leukemic progression.

Base Sequence↗

Functional analysis of clonally expanded CD8, TCR gamma delta T cells in a patient with chronic T-gamma lymphoproliferative disease.

Leukemic cells from a patient with T-gamma lymphocytosis were found to have the surface phenotype, CD3+, CD4-, CD8+, Leu19+, TCR delta 1+, WT31-. The clonal nature of the TCR gamma delta T cell proliferation was documented by flow cytometry and Southern blot analysis. Morphologically, they were large to medium-sized mature lymphocytes with cytoplasmic granules. Functionally, the cells revealed strong cytotoxic activities against NK-sensitive target cells, but had neither killer T cell activity nor suppressive activity on PWM-driven immunoglobulin synthesis by B cells. Interestingly, both suppressive and cytotoxic T cell activities were recovered with the depletion of CD8+ T cells. These studies may suggest some functions of the CD8+ population of human TCR gamma delta T cells in a normal immune system.

Aged↗

Aggressive natural killer cell leukaemia/lymphoma: report of four cases and review of the literature. Possible existence of a new clinical entity originating from the third lineage of lymphoid cells.

The morphologic, immunologic, genotypic and functional properties of peripheral blood and bone marrow cells or cultured cells from four patients with a clinically aggressive non-T, non-B natural killer cell leukaemia/lymphoma (ANKL/L) are described. The leukaemic cells possessed medium to large granules in the cytoplasm, antigens against CD38, CD2, OKIa 1 and NKH-1 CD56) monoclonal antibodies on their cell-surface, and also showed natural killer (NK) activity. In addition, these ANKL/L belonged to neither T- nor B-cell lineage, proved by studying clonal gene rearrangement for the T beta, T gamma and T delta receptors, and immunoglobulin. After comparing them with the seven cases of ANKL/L reported in other institutions, with regard to immunophenotype, genotype and function, we conclude that ANKL/L originating from a third lineage of lymphoid cells is a distinct clinical entity.

Adolescent↗

Depression in members of a new religious sect in Japan.

We investigated 226 people belonging to a regional church of a new religious sect (hereinafter referred to as religious group) and 899 ordinary people living in the rural area near this church (hereinafter referred to as nonreligious group) with a questionnaire using Zung's Self-Rating Depression Scale (SDS). In males ranging in age from 40 to 69, the mean scores of 7 SDS items out of 20 were significantly higher in the religious group than in the nonreligious group. Males at the age of 70 or older in both groups, however, did not show any significant difference in these items. It suggests that the religious affiliation exerted mentally good effects on the older male members.

Adaptation, Psychological↗

Survival and disinfection of adenovirus type 19 and enterovirus 70 in ophthalmic practice.

In an experimental model designed to simulate actual clinical situations, the risk period of adenovirus type 19 (AdV-19) and enterovirus 70 (EV-70) transmission by contaminated instruments has been investigated, as well as the effective methods of disinfection against these viruses. No EV-70 could be detected 6 hours after inoculation on applanation tips contaminated with viruses and naturally dried, indicating that drying the instruments and keeping them in a moisture-free environment is a convenient disinfection procedure against EV-70. In contrast, AdV-19 maintained its initial infectious level for 11 days on contaminated and subsequently dried tips. Both viruses when placed in eyedrop solutions at room temperature sustained their infectivity for more than 20 days. It was found that heating at 90 degrees C for 5 seconds is the most simple and effective disinfection against AdV-19 and EV-70. AdV-19 was about 60 times more resistant to ultraviolet irradiation than EV-70.

Adenoviruses, Human↗

Molecular analysis of T cell receptor and CD3 genes in CD3- large granular lymphocytes (LGLs): evidence for the existence of CD3- LGLs committed to the T cell lineage.

Seven patients with CD3- lymphoproliferative disorder of granular lymphocytes (LDGL) were analyzed for rearrangement of the T cell receptor (TCR) delta and alpha as well as gamma and beta genes. Among those patients six showed the germline configuration of all known rearranging TCR genes. Two analyzed patients of them lacked CD3-gamma transcripts and expressed nonfunctional TCR-beta transcripts. Meanwhile, TCR-delta gene rearrangement accompanied by expression of full-length TCR-delta transcripts was observed in one patient with CD3- LDGL. In addition, the cells from this patient transcribed the CD3-gamma gene which is one of the earliest events restricted to cells committed to the T cell lineage. These findings indicate that CD3- LGLs include not only cells belonging to the NK cell lineage but also precursor cells committed to the T cell lineage.

Antigens, Differentiation, T-Lymphocyte↗

[A study of drinking habits of rural middle and old aged residents in Ibaraki Prefecture--relationship between problem drinking, depression and personality (Part 1). On male subjects].

Although there has been considerable research conducted regarding the relationship between alcohol dependency and clinical depression, there have been few reports which have investigated the relationship between alcohol consumption and depression in the general populace of residents of rural communities in Japan. We investigated this correlation in a rural community located in Ibaraki Prefecture, the findings of which are described in this report. The subjects of this investigation were residents of the southern part of the town of K in Ibaraki Prefecture age 40 and over, all of whom had participated in a medical examination program. With respect to the men surveyed, the proportions of problem drinkers and severe problem drinkers were 10.4% and 25.7%, respectively. According to the results we obtained with respect to correlation with personality, problem drinkers were found most frequently in shut-in personality types (37.5%). In regard to the correlation with depression, 7% of the problem drinkers and severe problem drinkers exhibited an SDS score of 50 or higher. In addition, the non-drinking group demonstrated a significantly higher degree of depression in comparison to the normal drinker and severe problem drinker groups.

Aged↗

[A study of drinking habits of rural middle and old aged residents in Ibaraki Prefecture--relationship between problem drinking, depression and personality (Part 2). On female subjects].

In looking at the findings of the women subjects of this investigation, alcohol consumption decreased rapidly in younger women with the borderline being roughly at the age of 50 years. This is consistent with general trends in Japan. In terms of the correlation with personality, the proportion of drinkers in those groups consisting of syntonic, self-revelation, nervous and persistent personality types was high at 34-37%. 3 out of the 7 women who were severe problem drinkers were of the persistent personality type. As such, it is believed that depression contributes to problem drinking in middle-aged and elderly women residing in rural communities. According to the results of this investigation focused on women residing in rural communities, 30% of the severe problem drinkers were also suffering from depression. As this figure closely resembles the proportion noted in clinical investigations, it was suggested that in the process of alcoholism becoming involved with health care institutions, there are other contributing factors besides clinical depression.

Aged↗

[A case of necrotizing scleritis with angiitis of papilla].

A case of a 66-year-old woman suffering from polymyalgia rheumatica with necrotizing scleritis followed central retinal artery occlusion in the left eye was studied clinico-pathologically. The left eye was enucleated because of severe pain in spite of the steroid therapy, and was examined histopathologically. The necrotic granulomatous changes of the deep sclera in the ciliary body and peripheral fundus were observed. Lymphocytes, plasma cells and epitheloid cells infiltrated in the central retinal artery at the papilla. It seemed that subconjunctival injection of steroid had induced scleral necrosis. When scleritis is very severe, it might be suggested that systemic steroid should be given in large suppressive doses.

Female↗

Analysis of molecular events in leukemic cells arrested at an early stage of T-cell differentiation.

We analyzed the rearrangement and expression of T-cell receptor (TCR) genes, including the recently identified TCR delta gene, in 21 patients with T-lineage leukemia/lymphoma. Among 8 patients with CD3-, CD4-, and CD8- (group I), 2 patients showed germline configuration of the TCR delta, gamma, beta, and alpha genes and 1 patient demonstrated only TCR delta gene rearrangement. All nine patients with CD3-, CD4+, and/or CD8+ (group II) showed concomitant rearrangements of the TCR delta, gamma, and beta genes. TCR alpha gene rearrangement was also observed in two patients. Three of four patients with CD3+ (group III) showed rearrangement of the TCR alpha gene with deletion of both alleles or of a single allele of the TCR delta gene. With Northern blot analysis, full-length transcripts of the TCR delta gene were detected in 3 of 15 examined patients. All were restricted to group I or group II. In contrast, full-length transcripts of TCR beta and alpha were observed mainly in samples from groups II and III. Based on these findings, rearrangement of the TCR delta gene may be the earliest event in T-cell differentiation, preceding rearrangements of the other TCR genes.

Antigens, CD↗

Demonstration of clonal selection in a child with non-Hodgkin's lymphoma.

A 2-year-old boy with B-lineage non-Hodgkin's lymphoma is described. He presented with growing skin tumors on his head, and biopsy specimens showed a malignant lymphoma of diffuse lymphoblastic type. Sixty-four percent of bone marrow cells were replaced with lymphoblasts, and they expressed B-lineage markers (CD19 and HLA/DR). Southern blot analysis demonstrated immunoglobulin heavy chain gene rearrangements (two rearranged and one germline) with the germline configuration of the T-cell receptor beta chain gene. Ten months later he relapsed with blasts of M5 morphologic type and a myeloid phenotype with the germline configuration of the immunoglobulin genes. During the next 2 months, myeloid blasts with immunoglobulin gene rearrangement which was identically rearranged with one of the two rearranged bands detected at diagnosis appeared. The most likely explanation for these findings is that initially the patient seemed to have at least two different clones of blasts, and clonal selections occurred during the treatments.

Antigens, CD19↗

Poor prognosis of mediastinal non-Hodgkin's lymphoma with an immature phenotype of CD2+, CD7 (or CD5)+, CD3-, CD4-, and CD8-.

Nine children with mediastinal non-Hodgkin's lymphoma (NHL) were treated according to our new regimen which is characterized by intensified therapy with high-dose cytosine arabinoside (HDCA). After induction therapy with a combination of five drugs, such as vincristine, doxorubicin, cyclophosphamide, 1-asparaginase, and prednisolone, intermediate dosages of methotrexate (MTX) (1 g/m2) and HDCA (1.5 g/m2 x 12 doses) were administered. All but one patient (88.9%) achieved complete remission and then received this intensified therapy. With a median follow-up period of 25.5 months, five patients are still in complete remission, but three patients have relapsed. From the phenotypic point of view, these relapsed patients showed only very immature T-cell differentiation antigens such as CD2 and CD7 (or CD5). These results suggest that HDCA as intensified therapy for children with mediastinal NHL seems to be effective. However, for patients with an immature phenotype of T-lineage cells, more sophisticated regimens should be prepared.

Adolescent↗