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Biomedical subjects

K Usuku

Publications and source records attributed to K Usuku.

54 records · Page 3Linked to original sources
PubMed1994

[Immune response against myelin basic protein and analysis of T-cell receptor in multiple sclerosis].

Human demyelinating disease, multiple sclerosis, is now though to be caused by autoreactive T cells against several antigens in central nervous system. In experimental allergic encephalomyelitis, animal model of the disease, successful treatment is reported using a monoclonal antibody to T-cell receptor (TCR) of encephalitogenic T cells. Analoging this model, researchers are now trying to intervene T cells suspected to elicit the disease. For this purpose, myelin basic protein, one of the candidate CNS antigens, reactive T cells and usage of TCR in those cells are extensively examined. Although no convincing result was obtained so far because of complexity of the disease and a genetic background of human beings, T cell intervention may be beneficial to some patients with this disease.

Humans↗
PubMed1993

The T-cell response to myelin basic protein in familial multiple sclerosis: diversity of fine specificity, restricting elements, and T-cell receptor usage.

Indirect evidence suggests that an autoimmune response to myelin basic protein (MBP) may be involved in the pathogenesis of multiple sclerosis (MS). In MS, several reports have suggested that restricted T-cell populations respond to MPB, as in inbred rodents with the MS disease model experimental allergic encephalomyelitis. In experimental allergic encephalomyelitis, the T-cell repertoire to MBP varies between strains, and in MS it is likely that the response to MBP is also best defined under conditions where genetic differences between subjects are controlled. In this report, the fine specificity of the T-cell response to MBP was assessed in three families, each with multiple individuals affected with MS. We found that (1) comparable frequencies of MBP-reactive T-cell lines were obtained from peripheral blood of MS patients and their healthy siblings. Human leukocyte antigen (HLA) identical sibling pairs discordant for MS had similar frequencies of MBP-reactive T-cell lines. (2) A broad spectrum of MBP epitopes was recognized by T-cell lines from all individuals studied. Within a family, the fine specificity of MBP recognition showed little or no overlap between individuals, even between HLA identical siblings. (3) Recognition of MBP epitopes occurred in the context of different HLA class II alleles. At least four DR alleles each served as restricting elements for recognition of P82-101 or the carboxy terminal region of MBP, two regions thought to be important in the human T-cell response to the molecule. No relationship between the use of a particular DR allele and a response to a particular region of MBP could be established.(ABSTRACT TRUNCATED AT 250 WORDS)

Alleles↗
PubMed1993

The human T-cell receptor beta-chain repertoire: longitudinal fluctuations and assessment in MHC matched populations.

The influence of the environment and of the major histocompatibility complex (MHC) in shaping the human T-cell receptor beta-chain variable region (TCRBV) repertoire has not been systematically studied. Here, expression of TCRBV gene families was estimated by a sensitive polymerase chain reaction (PCR)-based method. Serial studies of peripheral blood, performed at 2-week intervals over a 3-month period, revealed that fluctuation in the expression of many TCRBV genes occurred in healthy individuals and in the absence of clinically evident infections. Fluctuation of TCRBV4, TCRBV5.2, TCRBV9, and TCRBV13.1 genes were present in all subjects. Additional TCRBV genes fluctuated in some but not in other individuals. Comparison of the TCRBV repertoire between these unrelated individuals indicated differences in the mean expression of TCRBV5.1, TCRBV9, TCRBV11, TCRBV15, TCRBV17, and TCRBV20 genes. For any TCRBV gene, intersubject differences were generally of a magnitude of twofold or less. Larger differences characterized the TCRBV repertoire of CD4 compared to CD8 cells. Some differences, for example over-representation of TCRBV2 and TCRBV5.1 on CD4, and TCRBV10, TCRBV14, and TCRBV16 on CD8 cells, were present in most subjects. Individuals homozygous for DR2- or DR3-bearing extended MHC haplotypes displayed similar individual variability of TCRBV expression. These data indicate that the circulating TCRBV repertoire in humans is both dynamic and diverse. Both environment and MHC effects contribute to the diversity of TCRBV expression.

Base Sequence↗
PubMed1992

T-cell receptors: germline polymorphism and patterns of usage in demyelinating diseases.

The genomic organization of the T-cell receptor (TCR) gene complexes accounts for many central aspects of T-cell immunobiology, including specificity and diversity. Recent data indicate that polymorphism of TCR genes is present within a species and may influence the immune phenotype of an individual. Such polymorphism has been detected by RFLP, by the presence of large regions of insertion or deletion of germline DNA, and by allelic variability of individual gene segments that are expressed. In addition to allelic variation of TCR genes, immune responses may also be influenced by the repertoire of the TCR molecules that are expressed by responding T-cell populations. In some situations, pathogenic T-cell responses may involve expression of limited numbers of TCR gene families. This is true, for example, in experimental allergic encephalomyelitis, an autoimmune nervous system disease mediated by T-cells reactive to myelin basic protein. In the human disease counterpart, multiple sclerosis, a more complex pattern of T-cell recognition to the putative autoantigen is generally present, although in some individuals a restricted response may occur. Specific therapies targeted to certain TCR molecules represents a promising approach to chronic inflammatory diseases in humans. The efficacy of such therapies will be determined in part by the TCR repertoire expressed in individual disease situations and by the potential for plasticity in the pathogenic T-cell response that may exist.

Alleles↗
PubMed1991

Inhibitory effect of maternal antibody on mother-to-child transmission of human T-lymphotropic virus type I. The Mother-to-Child Transmission Study Group.

In order to evaluate the protective role of the maternal antibody against mother-to-child transmission of HTLV-I, we followed a total of 780 children born to HTLV-I carrier mothers by investigating the level of anti-HTLV-I antibody transferred in utero, decline of the maternal antibody and seroconversion in post-natal life. The anti-HTLV-I antibody was positively detected within the first 3-6 months of life and declined at 6-12 months after birth in all children. After the maternal antibody declined, seroconversion occurred in some of the children following either breast feeding or bottle feeding. The seroconversion rates of short-term (less than or equal to 6 months) and long-term (greater than or equal to 7 months) breast feeders were 4.4% (4/90 cases) and 14.4% (20/139 cases), and the rate of bottle feeders was 5.7% (9/158 cases). Long-term breast feeding yielded more seroconverters than short-term breast feeding; 14.4% (20/139 cases) vs. 4.4% (4/90 cases), RR = 3.68, p = 0.018. The seroconversion rate of short-term breast feeders was nearly equal to that of bottle feeders; 4.4% (4/90 cases) vs. 5.7% (9/158 cases), RR = 0.770, p = 0.471. When neonatal lymphocytes were cultured with breast milk cells of HTLV-I carrier mothers, the in vitro infection of HTLV-I was inhibited by the addition of HTLV-I-seropositive cord-blood plasma. Our results suggest that the maternal antibody may inhibit HTLV-I infection by short-term breast feeding but not by long-term breast feeding after decline of the maternal antibody.

Adolescent↗
PubMed1991

Cytotoxic and suppressor activities in patients with HTLV-I-associated myelopathy.

Since there are several immune abnormalities and autoimmune-like features in human T-cell lymphotropic virus type I (HTLV-I)-associated myelopathy/HTLV-I-associated tropical spastic paraparesis (HAM/TSP), we examined cytotoxic and suppressor cell functions in HAM/TSP. In this study, we assayed cell-mediated cytotoxicity of CD8+ T-cell lines established from cerebrospinal fluid lymphocytes of two patients with HAM and concanavalin A-induced suppressor cell activities of peripheral blood lymphocytes from five patients with HAM. Our study revealed that three of four CD8+ T-cell lines showed cytotoxic activities against autologous CD4+ T-cell lines infected with HTLV-I, and two of the three lines showed major histocompatibility complex class I-restricted cytotoxicity. We also demonstrated that the concanavalin A-induced suppressor function was not defective in HAM patients. Therefore, the immune abnormalities and autoimmune-like features observed in HAM/TSP may not result from defective cytotoxic or suppressor cell activities.

Adult↗
PubMed1990

Association of a particular amino acid sequence of the HLA-DR beta 1 chain with HTLV-I-associated myelopathy.

Analyses of HLA-DRB1 gene using polymerase chain reaction and sequence-specific oligonucleotide probes reveal that the amino acid sequence Glu-Gln-Arg-Arg-Ala-Ala-Val at positions 69-75 of the third hypervariable region (HVR) of HLA-DR beta 1 chain is significantly associated with HTLV-I-associated myelopathy (HAM). Since the frequency of this sequence in HTLV-I carriers is almost the same as that in controls from Kagoshima (an endemic area of HTLV-I), this sequence may be related to susceptibility to HAM rather than to susceptibility to HTLV-I infection. Since this third HVR functions as putative antigen-binding sites and T cell recognition sites, the amino acid sequence of positions 68-73 was analyzed in detail. The analysis reveals that Gln70 and Arg71 are relevant to the occurrence of HAM.

Alleles↗
PubMed1990

Autoproliferative and self-reactive T-cell lines from patients with HTLV-I-associated myelopathy.

In two patients with human T lymphotropic virus type 1 (HTLV-I)-associated myelopathy (HAM) and a non-HAM HTLV-I carrier, T-cell lines were generated and characterized from cerebrospinal fluid (CSF) lymphocytes and peripheral blood lymphocytes (PBL). In total, 62 T-cell lines were established using direct plating technique for expanding human T lymphocytes. Sixty three percent of the T-cell lines were CD4+, CDw29+ and HTLV-I gag+. CD8+T-cell lines were also established and they were gag-. Proliferation in the absence of additional antigens and exogenous interleukin 2 ("autoproliferation") was observed in 61% of the T-cell lines and significantly correlated with HTLV-I antigen (gag) expression. In addition, some T-cell lines from HAM patients exhibited proliferative response to self PBL, and the magnitude of their responses was diverse according to the phenotypes of stimulating cells. Therefore, the spontaneous lymphoproliferation observed in patients with HAM is generated by three components; HTLV-I-infected T cells and T cells reactive against HTLV-I and against self antigens. Since most gag+ T-cell lines produced lymphotoxin (LT)/tumor necrosis factor alpha (TNF alpha), it is suggested that those T cells are playing important roles in the pathogenesis of HAM.

Cell Line↗
PubMed1989

HTLV-I-associated myelopathy and adult T-cell leukemia cases in a family.

Familial cases of HTLV-I-associated myelopathy (HAM) and adult T-cell leukemia (ATL), developing in a daughter and father, respectively, are reported. The coexistence of both diseases in a family has not been reported before. This supports the recent findings that ATL and HAM may be brought about by an identical virus on an apparently different immunogenetic background.

Adult↗
PubMed1989

[Oligoclonal IgG bands in patients with HTLV-I associated myelopathy--detection by agarose isoelectric focusing, transfer to cellulose nitrate and immunoperoxidase staining].

The patient with HTLV-I associated myelopathy (HAM) shows a quite uniform clinical picture characterized by slowly progressive spastic paraparesis, slight sensory disturbances and urinary frequency, and the pathogenetic relationship between spastic paraparesis and HTLV-I was established. Since then, the role of the virus in causing myelopathy has drawn increasing attention. However, we have little information about cerebrospinal fluid (CSF) abnormalities in patients with HAM. Analysis of CSF oligoclonal bands (OB) in 22 patients with HAM was reported. All of 22 patients had typical clinical signs and symptoms of HAM with high titers of anti-HTLV-I antibodies in the serum by particle agglutination method. And these antibodies against HTLV-I were confirmed by enzyme-linked immunosorbent assay and western blot. Detection or characterization of CSF OB was done by high resolution agarose gel (HARG) electrophoresis with silver staining and immunofixation method with immunostaining. Other method for detection OB was by agarose isoelectric focusing (IEF), transfer to cellulose nitrate and immunoperoxidase staining (Olsson, 1984). CSF OB was detected in 13 of 22 patients with HAM by the method of immunofixation, using HRAG. All of CSF OB reacted with peroxidase conjugated goat anti-human IgG serum. More than 3 oligoclonal bands were not detected in HRAG electrophoresis. However, CSF OB was detected in all of 22 patients by the method of Olsson (IEF, in agarose, double-antibody peroxidase labelling and avidin-biotin amplification). The majority of patients with HAM had at least 5 or more OB in the region between pH 6.8 and 9.5.(ABSTRACT TRUNCATED AT 250 WORDS)

Ampholyte Mixtures↗
PubMed1988

HLA haplotype-linked high immune responsiveness against HTLV-I in HTLV-I-associated myelopathy: comparison with adult T-cell leukemia/lymphoma.

HLA haplotypes of 27 patients with human T-lymphotropic virus type I (HTLV-I)-associated myelopathy (HAM) and 12 patients with adult T-cell leukemia/lymphoma (ATLL) were examined by analyzing HLA types of the patients and their family members. Either A11Bw54Cw1DR4DQw3, A24Bw54Cw1DR4DQ-, A24B7Cw7DR1DQw1, or A24Bw52Cw-DR2DQw1 and the related haplotypes were found in 70% of cases with HAM. None of these "HAM-associated" haplotypes was found in patients with ATLL. HLA haplotypes made up of HLA components of A26Bw62Cw3DR5DQw3 and one particular haplotype of Aw33B44Cw-DRw6DQw1 were associated with the ATLL haplotypes. These "ATLL-associated" haplotypes were also found in the patients with HAM who had no previous history of blood transfusion. The in vitro cultures of peripheral blood lymphocytes with HTLV-I virion antigens revealed that the response with HAM peripheral blood lymphocytes was remarkably higher than that with ATLL peripheral blood lymphocytes. Based on this HTLV-I-specific immune responsiveness, we can segregate the high responders in HAM (14 of 16 cases) and the low responders in ATLL (6 of 7 cases). The existence of high and low responders was also confirmed by the normal healthy individuals, whose responses were segregated with HAM-associated and ATLL-associated haplotypes. These results suggested that two ethnic groups in southern Kyushu may get the two different diseases, HAM and ATLL, because of their different immunogenetic backgrounds. The high immune response to HTLV-I seems to be an important genetic factor in the development of HAM.

Adult↗
PubMed1987

Chronic progressive myelopathy associated with elevated antibodies to human T-lymphotropic virus type I and adult T-cell leukemialike cells.

Six adult patients had a chronic progressive myelopathy that possessed the following features: high antibody titers to human T-lymphotropic virus type I (HTLV-I) in serum and cerebrospinal fluid (CSF); predominantly upper motor neuron disorder, symmetrical, with mild sensory and bladder disturbances; and presence of adult T-cell leukemia-like cells in both peripheral blood and CSF. We refer to this entity as HTLV-I-associated myelopathy (HAM). Electrophoretic studies of immunoglobulin G in CSF using Western blot analysis characteristically demonstrated p24 and p32 bands. Rates of intra-blood-brain barrier synthesis were determined and found increased in the patients with HAM. Corticosteroid treatment produced clinical improvement in all of 4 patients. A retrospective survey of CSF samples was carried out in 287 patients with neurological disorders, and 6 additional patients with HAM were identified.

Adrenal Cortex Hormones↗