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H Ikematsu

Publications and source records attributed to H Ikematsu.

At least 19 recordsLinked to original sources
PubMed2003

Age-related accumulation of Ig V(H) gene somatic mutations in peripheral B cells from aged humans.

To investigate age-related alterations in human humoral immunity, we analysed Ig heavy chain variable region genes expressed by peripheral B cells from young and aged individuals. Three hundred and twenty-seven cDNA sequences, 163 micro and 164 gamma transcripts with VH5 family genes, were analysed for somatic hypermutation and VHDJH recombinational features. Unmutated and mutated micro transcripts were interpreted as being from naive and memory IgM B cells, respectively. In young and aged individuals, the percentages of naive IgM among total micro transcripts were 39% and 42%, respectively. D and JH segment usage in naive IgM from aged individuals was similar to that from young individuals. The mutational frequencies of memory IgM were similar in young and aged individuals. gamma transcripts, which are regarded as being from memory IgG B cells, showed a significantly higher mutational frequency (7.6%) in aged than in young individuals (5.8%) (P < 0.01). These findings suggest that VHDJH recombinational diversity was preserved, but that the accumulation of somatic mutations in the IgG VH region was increased in aged humans. The accumulation of somatic mutations in IgG B cells during ageing may imply that an age-related alteration exists in the selection and/or maintenance of peripheral memory B cells.

Adult↗
PubMed2002

A reduction in the number of peripheral CD28+CD8+T cells in the acute phase of influenza.

Influenza patients show a high incidence of T lymphocytopenia in the acute phase of the illness. Since CD8+ T cells play an important role in influenza virus infection, we investigated which subset of CD8+ T cells was involved in this lymphocytopenia. CD8+ T cells from eight patients with influenza A were studied for lymphocyte count, surface marker, and intracellular IFN-gamma production in the acute (days 1-3) and recovery phases (days 9-12). Total and T lymphocyte counts in the acute phase were approximately three times less than in the recovery phase; however, the CD4/8 ratio was the same in both phases. The cell count reduction in the acute phase was attributed predominantly to the CD28+ CD8+ subset, compared with the CD28- CD8+ subset. The memory/activation marker CD45RO on the CD8+ T cells was assessed. The CD28+ CD45RO- subset, a naive phenotype, was reduced significantly in number in the acute phase compared with the recovery phase. The CD28+ CD45RO+ subset, a memory phenotype, was also reduced in the acute phase, but the reduction was not statistically significant. Intracellular IFN-gamma in the CD8+ subset after mitogenic stimulation was measured by flow cytometry; the percentage of CD28+ IFN-gamma-/CD8+ subset in the acute phase was significantly less than in the recovery phase. These results indicated that the predominant reduction of peripheral CD8+ T cells in the acute phase of influenza was from naive-type lymphocytes, suggesting that these quantitative and qualitative changes of CD8+ T cells in influenza are important for understanding the immunological pathogenesis.

Acute Disease↗
PubMed2001

Evidence of B cell clonal expansion in HIV type 1-infected patients.

HIV-1 infection results in a gradual decrease in CD4(+) T cell counts and progressive immune deficiency. Increased T cell turnover in HIV-1-infected patients, which can be interpreted as T cell clonal expansion, has been thought to be relevant to its pathogenesis. To investigate whether B cell clonal expansion also occurs in HIV-1-infected patients, we examined the expressed V(H)DJ(H) gene sequences of peripheral B cells in HIV-1-infected patients with hypergammaglobulinemia. Identical V(H)DJ(H) gene rearrangements with additional nucleotide differences in V(H) genes were analyzed as a marker of clonally related B cells. From healthy individuals and HIV-1-uninfected patients with hypergammaglobulinemia, clonally related B cells were detected in none of 10 (0%) and 2 of 10 (20%), respectively. No clonally related B cells were detected in any of the nine HIV-1-infected patients with detectable viral loads and normal Ig levels (0%). In contrast, from 9 of 14 HIV-1-infected patients with hypergammaglobulinemia (64%), clonally related B cells were detected. In addition, no HIV-1-infected patients who exhibited normal Ig levels after antiretroviral therapy had clonally related B cells. These findings suggest that B cell clonal expansion is present in HIV-1-infected patients with hypergammaglobulinemia.

Adult↗
PubMed2001

Hepatitis B virus genomes of chronic hepatitis patients do not contain specific mutations related to acute exacerbation.

To determine the specific viral variants associated with acute exacerbation of chronic hepatitis from hepatitis B virus (HBV) infection, we analyzed the complete nucleotide sequences of the HBV genome in serial serum samples from two chronic active hepatitis patients who seroconverted from HBeAg to anti-HBe. HBV DNA was amplified by polymerase chain reaction (PCR) and sequenced. A 1896 precore stop codon mutant (G to A at nt 1896) coexisting with the wild sequence was found in both patients prior to seroconversion from HBeAg to anti-HBe. Core promoter mutations at nucleotide positions 1762 (A to T) and 1764 (G to A) were found in both patients throughout the observation period. Mutations were observed in the HBV genome of the two patients at different time points, and there was no correlation between the mutations and liver disease or DNA polymerase levels. The nucleotide divergence rate and the composition of quasispecies in the HBV sequence at the time of acute exacerbation were almost the same as were found at other time points. These results suggest that acute exacerbation does not appear to be caused by a characteristic HBV species. The multiple factors that cause generalized HBV replication activation may contribute to acute exacerbation.

Child, Preschool↗
PubMed2001

[Reduction of medical resources utilization by influenza vaccination for hospitalized elderly patients].

In order to evaluate the economic efficacy of influenza vaccination for the elderly inpatients, we have investigated the health insurance fee of elderly inpatients in Japan. It was revealed that the health insurance fee varied by patients largely, ranging from 7,000 yen to 90,000 yen. Primary reason of this variation was due to the existence of the same effective drugs with variant prices and there were no rules concerning the period of drug medication. Thus, it was found that it would be improper to use the medication fee as a measure in evaluating the effects of influenza vaccinations. In this study, we used the length of days of testing and medication such as oral antibiotics, blood cell count, etc. as a measure to evaluate the effect of influenza vaccination. We compared these measures among elderly hospitalized patients with influenza vaccination or without influenza vaccination by ADL. Mean length of days of oral antibiotics was 2.64 (+/- 6.40) days for those with vaccination, and 3.92 (+/- 7.31) days for those without vaccination. Mean length of days of injection antibiotics was 2.52 (+/- 5.53) days for those with vaccination, and 8.82 (+/- 15.1) days for those without vaccination. Mean length of days of cells blood counter was 2.63 (+/- 2.22) days for those with vaccination, and 4.44 (+/- 3.20) days for those without vaccination. Mean length of days of chest X-ray was 1.30 (+/- 2.07) days for those with vaccination, and 2.56 (+/- 3.49) days for those without vaccination. These results suggest that influenza vaccination reduces medical utilization of resources. It was also revealed that influenza vaccination is most effective when elderly patients who are bed-bound are vaccinated.

Aged↗
PubMed2001

[Effect of highly active antiretroviral therapy (HAART) on hypergammaglobulinemia in HIV infected patients].

To investigate the mechanism of hypergammaglobulinemia in HIV infected patients, the effect of highly active antiretroviral therapy (HAART) on the hypergammaglobulinemia was analyzed. Involved in this study were 34 untreated, 21 HAART-effective (complete response) and 14 HAART-non-effective (partial response) patients. Serum levels of HIV-RNA and gammaglobulin and immunoglobulin (Ig) isotypes were measured. Mean HIV-RNA levels of untreated and partial response patients were 1.6 x 10(4) copies/ml and 0.4 x 10(4) copies/ml, respectively. HIV-RNA levels of all complete response patients were below 4.0 x 10(2) copies/ml. Mean gammaglobulin percentages of untreated, partial response and complete response patients were 24.4%, 21.8% and 17.9%, respectively (p < 0.01 in untreated vs complete response patients). Mean IgG levels in the three groups were 2,489 mg/dl, 1,947 mg/dl and 1,618 mg/dl, respectively (p < 0.001 in untreated vs complete response patients). IgA levels were high in some untreated patients and lower in complete response patients. IgE levels were increased in some untreated and partial response patients, but there was no significant difference among the three groups. These results suggested that the hypergammaglobulinemia found in HIV infected patients was associated with HIV replication. The activation mechanism might differ by Ig isotypes.

Adult↗
PubMed2000

Structure-function analysis of a lupus anti-DNA autoantibody: central role of the heavy chain complementarity-determining region 3 Arg in binding of double- and single-stranded DNA.

To determine the contribution of the somatic point mutations and that of the complementarity-determining region (CDR)3 Arg to DNA binding, we engineered the germline V(H) and V(kappa) gene revertant and site-mutagenized the CDR3 Arg residues of the mutated and "antigen-selected" mAb 412.67. This anti-DNA autoantibody was derived from B-1 cells of a lupus patient and bore two H-CDR3 Arg, Arg105 and Arg107, encoded by N segment additions, and one kappa-CDR3 Arg, Arg97, resulting from a point mutation (Kasaian et al. 1994. J. Immunol. 152: 3137-3151; Kasaian et al. 1995. Ann. N.Y Acad. Sci. 764: 410-423). The germ-line revertant bound double-stranded (ds) DNA and single-stranded (ss) DNA as effectively as its wild-type counterpart (relative avidity: 6.4x10(-7) and 9.9x10(-9) vs. 6.7x10(-7) and 9.1 x10(-9) g/microl), raising the possibility that an antigen other than DNA was responsible for the selection of the mAb 412.67 V(H) and V(kappa) point mutations. H-CDR3 Arg105 and Arg107 were both required for dsDNA binding, but either Arg105 or Arg107 was sufficient for ssDNA binding. The central role of Arg105 and Arg107 in DNA binding reflected their solvent-exposed orientation at the apex of the H-CDR3 main loop. Consistent with its inward orientation afar from the antigen-binding surface, the kappa-CDR3 Arg97 played no role in either dsDNA or ssDNA binding.

Amino Acid Sequence↗
PubMed2000

Nucleotide variations amongst V(H)Genes of AMA-producing B cell clones in primary biliary cirrhosis.

Primary biliary cirrhosis, a chronic liver disease characterized by progressive inflammatory destruction of intrahepatic bile ducts, is also characterized by the presence of antimitochondrial antibodies (AMA). The predominant autoantibody is directed at the E2 component of pyruvate dehydrogenase (PDC-E2). Recent studies of this autoantibody response have analysed immunoglobulin-variable regions of human monoclonal antibodies and provided evidence for antigen-driven clonal selection. However, the number of clones analysed has been very limited and the presence of somatic mutations not formally proven. In this study, we took advantage of three stable B cell lines producing human IgG anti-PDC-E2 mAbs from a patient with PBC. We analysed the V(H)and V(L)gene structure of these reagents and, in addition, analysed 10 V(H)-D and D-J(H)sequences over a period of nearly 3 years. The expressed Ig V regions of the heavy chain (V(H)) and the light chain (V(L)) genes of mAb18, mAb37, and mAb82 utilized the V(H)III-VlambdaI, V(H)IV-VlambdaIII, and V(H)IV-V(k)IV gene families, respectively. The utilized gene elements were Ig gene elements that were found frequently in other antibodies with different specificity and affinity. Presence of somatic point-mutations was confirmed in mAb82 by comparison of the expressed V(H)gene sequence with that of corresponding germline V(H)gene obtained from the granulocyte genomic DNA of the same patient. Interestingly, clonally related B cells were consistently found throughout the observation period and nucleotide variations among the V(H)genes were very few, ranging from 0.19 to 0.72% per base. These findings suggest that long-lived B cell clones can exist and may contribute, at least in part, to maintenance of autoantibodies in humans.

Amino Acid Sequence↗
PubMed2000

Ongoing hypermutation in the Ig V(D)J gene segments and c-myc proto-oncogene of an AIDS lymphoma segregates with neoplastic B cells at different sites: implications for clonal evolution.

To investigate the role of somatic Ig hypermutation in the evolution of AIDS-associated B cell lymphomas, we analyzed the Ig V(D)J and c-myc genes expressed by neoplastic B cells in two extranodal sites, testis and orbit, and clonally related cells in the bone marrow. Testis and orbit B cells expressed differentially mutated but collinear V(H)DJ(H), V kappa J kappa and c-myc gene sequences. Shared mutations accounted for 10.2%, 8.4%, and 4.3% of the overall V(H)DJ(H), V kappa J kappa, and c-myc gene sequences. Tumor-site specific V(H)DJ(H), V kappa J kappa, and c-myc mutations were comparable in frequency, and a single point-mutation gave rise to an EcoRI site in the testis c-myc DNA. Both shared and tumor site-specific V(H)DJ(H), V kappa J kappa, and c-myc mutations displayed predominance of transitions over transversions. The "neoplastic" V(H)DJ(H) sequence was expressed by about 10(-5) cells in the bone marrow, and contained two of the three orbital, but none of the testicular V(H)DJ(H) mutations. The nature and distribution of the Ig V(D)J mutations found in the kappa chain suggested a selection by antigen in testis and orbit. Our data suggest that, in AIDS-associated B cell lymphomas, the Ig hypermutation machinery targets V(H)DJ(H), V kappa J kappa, and c-myc genes with comparable efficiency and modalities.

Adult↗
PubMed2000

[The efficacy of influenza vaccine among geriatric inpatients].

To investigate the efficacy of influenza vaccine in the elderly, hemagglutination inhibition (HI) antibody titer for the three types of influenza viruses were measured and the influenza infection rate was determined serologically in geriatric inpatients. Influenza vaccination was done for inpatients. For patients who had influenza vaccination in the year prior to the study, influenza vaccine was administered once or twice, and the number of injections were determined randomly. Influenza vaccine was injected twice to those had not received influenza vaccine in the previous year. Serum samples were collected from 166 vaccinated and 104 unvaccinated patients before and after 1996/1997 influenza season. In the vaccinees who had been vaccinated the previous year, 56 patients were injected once and 58 patient were injected twice. Fifty-two patients had not been vaccinated the previous year. Serologically diagnosed influenza infection rate in the 104 unvaccinated patients was 16.3% for influenza A/H3N2 and 8.7% for influenza B. The infection rate was 3.0% for influenza A/H3N2 and 0.6% for influenza B in the 166 vaccinated patients. The infection rates were significantly lower in the vaccinees than in the unvaccinated patients (p < 0.001 with A/H3N2 and p < 0.01 with B). There was no significant difference in the infection rate among the three vaccinated groups. These results suggest that the influenza vaccination had significant protective efficacy for influenza infection in the elderly. Prior vaccination did not diminish the efficacy of the influenza vaccine. The efficacy of a single influenza vaccine injection was equivalent to that of two injection.

Aged↗
PubMed2000

[The clinical feature of febrile episodes].

Institutionalized elderly patients are at risk of nosocomial infection because of their compromised status by aging. To clarify the relationship between fever and disease in elderly patients, we analyzed 1,105 febrile episodes, the etiology of which were already diagnosed, of 443 patients (136 men, 307 women). All patients who were 65 years of age or older and who had been admitted to the hospital for more than 7 days had fevers above 37.5 degrees C recorded. The etiologies of the 1,105 febrille episodes were respiratory tract infection in 381 (34.5%), urinary tract infection in 263 (23.8%), other diseases in 164 (14.8%) and in 297 (26.9%) unknown. The episodes were categorized into two groups by the degree of initial fever: group A, 559 episodes (50.6%) of 37.5-38.0 degrees C and group B, 546 episodes (49.4%) of above 38.0 degrees C. Of the episodes, 41.0% were one-day fevers, 21.4% two-day fevers, and 14.0% three-day fevers. The frequency of two-or-more-day fevers was significantly higher in group B (69.0%) than in group A (49.2%) (p < 0.001). In group B, respiratory tract infection (44.3%) was more frequent than urinary tract infection (16.1%) (p < 0.001). Of the respiratory tract infections, 63.5% were in group B and, in contrast, 66.5% of the urinary tract infections were in group A. The white blood cell count and C-reacting protein levels were significantly higher in group B than in group A (p < 0.001). The degree of initial fever is an important predictive marker of severity of disease in elderly patients.

Aged↗
PubMed2000

[Amantadine usage for influenza A during an influenza outbreak in a nursing home].

An outbreak of an influenza like illness was found in a nursing home in Fukuoka in January, 1999. Results of hemagglutinin inhibition tests with paired sera of patients and rapid diagnosis kit for influenza A indicated that an influenza A (H3N2) outbreak had occurred. A total of 15 patients with influenza like illness from one residential area of the nursing home were administered amantadine, 100 mg per day for five days. Clinical records of 264 residents were surveyed retrospectively from the tenth to the thirty-first of January, 1999. Influenza like illness was found in 112 residents (42.4%). The incidence of influenza like illness differed by residential area, ranging from 27.6% to 54.0%. The mean duration of fever was 3.6 days among patients administered amantadine. The mean duration was 4.4 days for patients not administered amantadine. The incidence of influenza like illness decreased rapidly after amantadine administration in the residential area where amantadine administration was done. These results suggest that amantadine is effective in mitigating influenza symptoms in the elderly. Amantadine may be useful for diminishing the influence of influenza A outbreaks in nursing homes.

Aged↗
PubMed2000

[Clinical features of influenza in the aged].

Influenza is a serious disease for the elderly. Influenza causes high fever in the elderly, similar as in healthy adults. Cough lasts longer, but frequency and degree of sore throat and coryza is lower in the elderly. Rapid diagnosis kits based on enzyme-linked immunoassay contribute to quick diagnosis, improving treatment of the elderly. Amantadine can mitigate various symptoms and hastens recovery. Other newly developed neuraminidase inhibitors are also hopeful for treatment. The poor prognosis of influenza in the elderly is associated with a high frequency of pneumonia complications. Decreased serum albumin level is a risk factor for post-influenza pneumonia. To reduce excess influenza death in the elderly, prophylaxis and management of the general health condition of elderly patients may be most important.

Aged↗
PubMed1999

[Efficacy of influenza vaccine among geriatric inpatients: effect of previous vaccination and antibody induction by single and twice injections].

To investigate the effect of previous influenza vaccination and the difference in antibody induction by single and twice injection of influenza vaccine in the elderly, hemagglutination inhibition (HI) antibody titers of the three types of influenza viruses were measured. Influenza vaccination was done for 217 inpatients. For the patients who had influenza vaccination in the year prior to the study, influenza vaccine was administered once to 77 patients and twice to another 70 patients. Influenza vaccine was injected twice to 70 patients who had not received influenza vaccine in the previous years. The influenza vaccine induced an increase in HI titer in almost all patients. The geometric mean of the HI titer and the frequency of patients with HI titers over 128x were similar after vaccination in the groups of patients who were injected twice, irrespective of whether or not influenza vaccination was given in the year prior to the study. The geometric means of the HI titers for influenzas A/H3N2 and B and the frequency of HI titers over 128x for influenza A/H3N2 after vaccination were lower in the patients who received vaccine once than in the patients vaccinated twice. These results suggest that prior vaccination does not diminish antibody response to influenza vaccine significantly in the elderly when influenza vaccine is injected twice. Although single injection is inferior to twice injection in antibody induction with some vaccine virus strains, induction of HI titers over 128x is found in more than 70% of elderly. Single injection of influenza vaccine may be practically effective and useful for protection of influenza infection in the elderly.

Aged↗
PubMed1999

[Evaluation of a rapid enzyme immunoassay for detection of influenza A virus among adult and elderly patients].

Directigen Flu A, an enzyme immunoassay membrane test for the detection of influenza A virus, was compared with serum hemagglutinine inhibition assay in adult and elderly patients. Throat specimens were collected by vigorous swabbing from febrile patients who were suspect for influenza by clinical symptoms and tested with Directigen Flu A. Serum samples were collected from the patients at onset of illness and two to eleven weeks later and tested for antibody titer to influenza A/H1N1, A/H3N2, and B. A total of 57 patients were involved in this study; 32 under 59 years of age and 25 over 60 years of age. Influenza was diagnosed in 42 patients by HI titer elevation (73.7%). Directigen Flu A was positive in 25 patients. Results of Directigen Flu A and HI test agreed in 40 patients. Sensitivity and specificity of Directigen Flu A were 59.5% (25/42) and 100% (15/15), respectively. There was no significant difference in sensitivity between the two age groups. These results indicate the potential usefulness of Directigen Flu A in the surveillance of influenza A infection in the geriatric population. Directigen Flu A gives results within 15 minutes without expensive equipment. Use of Directigen Flu permits the timely administration of antiviral therapy and infection control among hospitalized and institutionalized geriatric patients.

Adult↗
PubMed1998

Clonal analysis of a human antibody response. III. Nucleotide sequences of monoclonal IgM, IgG, and IgA to rabies virus reveal restricted V kappa gene utilization, junctional V kappa J kappa and V lambda J lambda diversity, and somatic hypermutation.

In previous work, we generated four IgM, five IgG1, and one IgA1 mAbs to rabies virus using B cells from four subjects vaccinated with inactivated rabies virus, a thymus-dependent (TD) mosaic Ag, and sequenced the mAb V(H)DJ(H) genes. Here, we have cloned the V kappa J kappa and V lambda J lambda genes to complete the primary structure of the Ag-binding site of these mAbs. While the anti-rabies virus mAb selection of VA genes (2e.2.2 twice, DPL11, and DPL23) reflected the representation of the V lambda genes in the human haploid genome (stochastic utilization), that of V kappa genes (O2/O12 twice, O8/O18, A3/A19, A27, and L2) did not (p = 0.0018) (nonstochastic utilization). Furthermore, the selection of both V kappa and V lambda genes by the anti-rabies virus mAbs vastly overlapped with that of 557 assorted V kappa J kappa rearrangements, that of 253 V lambda J lambda rearrangements in lambda-type gammopathies, and that of other Abs to thymus-dependent Ags, including 23 anti-HIV mAbs and 51 rheumatoid factors, but differed from that of 43 Abs to Haemophilus influenzae type b polysaccharide, a prototypic thymus-independent (TI) Ag. The anti-rabies virus mAb V kappa J kappa and V lambda J lambda segments displayed variable numbers of somatic mutations, which, in mAb58 and the virus-neutralizing mAb57, entailed a significant concentration of amino acid replacements in the complementarity-determining regions (p = 0.0028 and p = 0.0023, respectively), suggesting a selection by Ag. This Ag-dependent somatic selection process was superimposed on a somatic diversification process that occurred at the stage of B cell receptor for Ag rearrangement, and that entailed V gene 3' truncation and N nucleotide additions to yield heterogeneous CDR3s.

Amino Acid Sequence↗
PubMed1998

[Febrile episodes in elderly inpatients--a one year survey to determine the causes of fever in hospital].

To determine the cause of nosocomial infections, all febrile episodes of hospitalized elderly patients aged 65 and older at a hospital in Fukuoka City were categorized between April 15 1994 and April 14 1995. A febrile episode was a temperature above 37.5 degrees C after 7 consecutive days of normal body temperature (below 37.5 degrees C). Various clinical tests including blood examination, urinalysis, chest radiography and bacterial culture were done on the first and 7th day of the fever. A total of 1105 episodes in 443 patients (male 136, female 307) fulfilled this criteria for fever. The fevers were mainly due to respiratory tract (381 cases, 34.5%) and urinary tract infections (263 cases, 23.8%). There were 135 infections (12.2%) of other kinds and 297 cases (26.9%) that were classified as unknown. Approximately 70% of the febrile episodes were caused nosocomial infections, suggesting increased risk of infection in the hospitalized elderly and the importance of early detection of febrile changes in elderly inpatients.

Age Factors↗