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Biomedical subjects

K Hiromatsu

Publications and source records attributed to K Hiromatsu.

At least 55 records · Page 3Linked to original sources
PubMed1994

Inhibition of skin xenograft rejection by depleting T-cell receptor alpha beta-bearing cells without T-cell receptor gamma delta-bearing cells or natural killer cells by monoclonal antibody.

We compared the effects of in vivo administration of the anti-T-cell receptor (TCR) alpha beta monoclonal antibody (mAb) (H57-597) to those of the anti-CD3 mAb (145-2C11), with or without anti-NK1.1 mAb (PK136), on xenogeneic skin graft survival in mice. In anti-TCR alpha beta mAb-treated B6 mice, F344 rat skin grafts survived for about 54 days, whereas in anti-CD3 mAb-treated B6 mice with or without anti-NK1.1 mAb treatment grafts survived about 25 days. In anti-TCR alpha beta mAb-treated B6 mice, TCR alpha beta-bearing T-lymphocyte function was completely abrogated, although TCR gamma delta-bearing T-lymphocyte function was still intact on day 9. In the anti-CD3 mAb-treated mice, the functions of both types of T lymphocytes were completely abrogated. On day 32, when most of the skin xenografts had been rejected in the anti-CD3 mAb-treated mice, the functions of both T lymphocytes had recovered considerably, and could actually respond to F344 antigens. In contrast, the function of TCR alpha beta-bearing cells had only partially recovered in the anti-TCR alpha beta mAb-treated mice. Finally, natural killer (NK) activity in the anti-TCR alpha beta mAb-treated mice was intact on day 32, when rat skin grafts still survived. In contrast, NK activity in the anti-CD3 mAb plus anti-NK1.1 mAb-treated mice did not recover on day 32, when skin xenografts had already been rejected. These results suggest that TCR gamma delta-bearing T cells and NK cells by themselves, at least in the absence of TCR alpha beta-bearing T cells, do not mediate xenogeneic skin graft rejection in mouse/rat combinations.

Animals↗
PubMed1994

[The involvement of gamma delta T cells in neurological disorders].

Several studies have demonstrated that gamma delta T cells increased during infections with various Pathogens. A significant fraction of these gamma delta T cells are specialized in recognizing mycobacterial antigen, in particular, 65 kda heat-shock protein (Hsp), which is highly conserved between bacteria and eukaryotes. The demonstrated immunogenicity of a number of hsp has led to their being implicated in diseases of possible autoimmune etiology. A possible role of gamma delta T cells in human autoimmune diseases such as rheumatoid arthritis, diabetes, polymyositis, sarcoidosis and acute or chronic multiple sclerosis has been previously proposed. In this brief review, we summarized the current understandings of the immunobiology of gamma delta T cells focusing on the involvement of autoimmune processes.

Animals↗
PubMed1994

Analysis of the role of natural killer cells in Listeria monocytogenes infection: relation between natural killer cells and T-cell receptor gamma delta T cells in the host defence mechanism at the early stage of infection.

We have reported that T cells bearing T-cell receptors (TcR) of gamma delta type (gamma delta T cells) appear in the peritoneal cavity in a relatively early stage of primary intraperitoneal (i.p.) Listeria monocytogenes infection, and play a significant role against the infection. To elucidate the protective role of natural killer cells which also appear in the early stage of L. monocytogenes infection, mice were treated with anti-NK1.1 monoclonal antibody (mAb) to deplete NK cells before the infection. They exhibited accelerated clearance of L. monocytogenes, accompanied by enhanced induction of gamma delta T cells in the peritoneal cavity compared with non-treated mice. When the mice were depleted of gamma delta T cells by in vivo administration of anti-TcR gamma delta mAb, the bacterial burdens of organs from infected mice were not affected by NK cell depletion. These results suggest that, although NK cells increase significantly during the early stage of L. monocytogenes infection, they do not take part in the early host resistance against i.p. L. monocytogenes infection. It is also suggested that increased gamma delta T cells in the peritoneal cavity of NK cell-depleted mice can be one of the factors responsible for the enhanced clearance of L. monocytogenes in the early stage of infection.

Animals↗
PubMed1994

Inhibition of allograft rejection by anti-T-cell receptor-alpha beta monoclonal antibodies preserving resistance to bacterial infection.

Anti-CD3 monoclonal antibody (mAb) has been administered in clinical organ transplantation to reverse acute allograft rejection; however, severe immunodeficiency can result from such mAb treatment and cause an increased incidence of opportunistic infections. Therefore, new model systems are required in order to establish better methods for suppressing allograft rejection while preserving resistance to opportunistic infections. In this study, we compared the effects of the in vivo administration of anti-T-cell receptor-alpha beta (TcR alpha beta) mAb, H57-597, with those of anti-CD3 mAb, 145-2C11. Much to our surprise, the in vivo administration of anti-TcR alpha beta mAb prior to skin grafting led to a longer allograft survival than that of anti-CD3 mAb at any of the comparable dosages examined. In the lymphoid organs of mice treated with anti-TcR alpha beta mAb, TcR alpha beta-bearing cells were almost completely depleted, while TcR gamma delta-bearing cells remained at a relatively increased level on day 14 after anti-TcR alpha beta mAb treatment. The in vitro stimulation by anti-TcR gamma delta mAb clearly showed that such TcR gamma delta-bearing cells were functionally intact. Furthermore, the mice treated with anti-TcR alpha beta mAb, but not anti-CD3 mAb, were observed to be resistant to infection with Listeria monocytogenes. Finally, treatment with H57-597, but not with 145-2C11, led to a marked prolongation of skin allograft survival in the thymectomized mice. These results strongly suggest that anti-TcR alpha beta mAb, which partially preserved anti-bacterial resistance, may be more effective in preventing graft rejection than anti-CD3 mAb in the periphery, and indicate that anti-TcR alpha beta mAb may thus be potentially applicable for human transplantation. In addition, these results also indicate that the TcR gamma delta-bearing cells alone, at least in the absence of TcR alpha beta-bearing cells, do not contribute to allograft rejection in vivo.

Animals↗
PubMed1993

Peritoneal gamma delta T cells induced by Escherichia coli infection in mice. Correlation between Thy-1 phenotype and host minor lymphocyte-stimulating phenotype.

We found that gamma delta T cells increased in number in the peritoneal cavity after i.p. inoculation with Escherichia coli (ATCC 26) in mice. The increase of the gamma delta T cells was most prominent on day 5 after inoculation when the pathogens had been already eliminated from the hosts. Two-color flow cytometric (FCM) analysis revealed that these gamma delta T cells in infected C57BL/6 mice expressed Thy-1 Ag on their cell surface. On the other hand, gamma delta T cells induced by E. coli inoculation in C3H/He mice contained Thy-1-negative gamma delta T cells in addition to the Thy-1-positive gamma delta T cells. In both strains, irrespective of Thy-1 Ag expression, these gamma delta T cells were CD5 negative, CD44 positive, L-selectin negative, Ly-6C negative, and IL-2R low positive. Analyses of peritoneal exudate cells (PEC) from several other strains of mice after E. coli inoculation suggested that Thy-1-negative gamma delta T cells appear in mice carrying endogenous superantigen specific for V beta 3, especially mammary tumor virus-6. These findings suggest that Thy-1 Ag expression on the gamma delta T cells appearing in the peritoneal cavity after i.p. E. coli inoculation is correlated to the Mls phenotype of the host mice.

Animals↗
PubMed1993

Specificity of mutations induced by N-methyl-N-nitrosourea in a cDNA of the hprt gene.

N-Methyl-N-nitrosourea (MNU) reacts with DNA to produce a variety of lesions, of which O6-methylguanine (O6-MeG) has been implicated in the mutagenic and carcinogenic effects of this agent. The present study aimed to investigate the types and position specificities of mutations induced by MNU. Mutational sequence alterations were determined for 53 independent mutations induced by MNU in a cDNA of the human hprt gene, which is stably integrated into chromosomes of the mouse cell line VH12. The majority of the mutations induced by MNU were base substitutions (85%), mostly GC to AT transitions (41/43), and the remainder (15%) were frameshift or deletion mutations resulting from loss or addition of a few bases. The transition mutations occurred preferentially at the middle G in 5'-purine-G-N-3' sequences in the non-transcribed strand, and were distributed nonrandomly over the coding region of the gene. Analysis of the results suggests that, when interpreting mutational specificity and distribution, not only the nature of the mutational target sequence, but also the functional domains of the protein should be considered.

Amino Acid Sequence↗
PubMed1993

Characterization of T-cell receptor gamma delta T cells appearing at the early phase of murine Listeria monocytogenes infection.

It has been shown that T-cell receptor (TcR) gamma delta + CD4- CD8- T cells increase in number and have an important role in early protection in murine Listeria monocytogenes infection. In this report, to characterize further the phenotype of the gamma delta T cells in listeriosis, we analysed V region gene usage and in vitro antigen recognition of the TcR gamma delta T cells in the peritoneal cavity of mice at the early phase after i.p. infection with a sublethal dose of L. monocytogenes. The gamma delta T cells predominantly expressed V delta 6 which has been reported to be expressed by TcR gamma delta-bearing foetal thymocyte hybridomas specific to mycobacterial and self heat-shock protein (hsp) 60. These early appearing CD3+ CD4- CD8- T cells in Listeria-infected mice, which were reported to be TcR gamma delta T cells, increased in proportion and in size by in vitro stimulation with recombinant hsp 60 from Mycobacterium bovis and purified protein derivative from M. tuberculosis but not by stimulation with heat-killed L. monocytogenes. A 65,000 MW molecule was detected in the lysate of viable L. monocytogenes but not in the lysate of heat-killed L. monocytogenes by a monoclonal antibody (mAb) raised against mycobacterial hsp 60. These results suggest that the V delta 6-bearing peripheral gamma delta T cells are activated by recognizing listerial hsp 60 expressed by viable L. monocytogenes. The hsp 60-reactive V delta 6-bearing T cells may have an important role in protection against L. monocytogenes and other parasites that express hsp 60 at high level.

Animals↗
PubMed1992

Sequential analysis of T cells in the liver during murine listerial infection.

Phenotypes and functions of T cells in the liver were studied after an i.p. inoculation with viable Listeria monocytogenes in mice. T cells in the liver of untreated C3H/HeN mice (C3H; H-2k, Mls-2a) contain Thy-1.2+TCR-alpha beta + cells as a majority and Thy-1.2+TCR-gamma delta + cells and Thy-1.2-TCR-gamma delta + cells as minorities. The liver of untreated C3H mice did not contain T cells expressing V beta 3 and V beta 11, which are potentially autoreactive against self-superantigens of Mls-2a and Dvbl, respectively. On days 3 to 6 after infection, Thy-1.2-CD4lowTCR-alpha beta + T cells or Thy-1.2-TCR-gamma delta + T cells increased significantly in number and proportion in the liver whereas T cells with these phenotypes were hardly detected in the spleen, lymph nodes, peripheral blood, and peritoneal cavity during the course of the infection. The Thy-1.2-CD4lowTCR-alpha beta T cells contained V beta 3 or V beta 11-bearing cells in high frequencies. The potentially autoreactive V beta 3- or V beta 11-bearing T cells disappeared from the liver on day 7 after infection. Furthermore, the V beta 3+ and V beta 11+ cells but not V beta 8+ cells disappeared after culture for 24 h at 37 degrees C. In vitro stimulation of liver T cells using anti-V beta 11 mAb showed no proliferative response. These results suggest that the potentially autoreactive clones with Thy-1.2-CD4low phenotypes, which increased in number after listerial infection, may be anergized after interaction with self-Ag and may be programmed to die. These potentially autoreactive clones induced in the liver of Listeria-infected mice may not be functionally relevant to the host defense against Listeria.

Animals↗
PubMed1992

A protective role of gamma/delta T cells in primary infection with Listeria monocytogenes in mice.

We have previously reported that T cells bearing T cell receptors (TCRs) of gamma/delta type appear at a relatively early stage of primary infection with Listeria monocytogenes in mice. To characterize the early-appearing gamma/delta T cells during listeriosis, we analyzed the specificity and cytokine production of the gamma/delta T cells in the peritoneal cavity in mice inoculated intraperitoneally with a sublethal dose of L. monocytogenes. The early-appearing gamma/delta T cells, most of which were of CD4-CD8- phenotype, proliferated and secreted IFN-gamma and macrophage chemotactic factor in response to purified protein derivative from Mycobacterium tuberculosis, or recombinant 65-kD heat-shock protein derived from M. bovis but not to heat-killed Listeria. To further elucidate the potential role of the gamma/delta T cells in the host-defense mechanism against primary infection with Listeria, we examined the effects of in vivo administration of monoclonal antibodies (mAbs) against TCR-gamma/delta or TCR-alpha/beta on the bacterial eradication in mice infected with Listeria. Most of alpha/beta T cells or gamma/delta T cells were depleted in the peripheral lymphoid organs at least for 12 d after an intraperitoneal injection of 200 micrograms TCR-alpha/beta mAb or 200 micrograms TCR-gamma/delta mAb, respectively. An exaggerated bacterial multiplication was evident at the early stage of listerial infection in the gamma/delta T cells-depleted mice, whereas the alpha/beta T cell-depleted mice exhibited much the same resistance level as the control mice at this stage although the resistance was severely impaired at the late stage after listerial infection.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Sequential appearance of gamma/delta- and alpha/beta-bearing T cells in the peritoneal cavity during an i.p. infection with Listeria monocytogenes.

To search for a potential role of T cell antigen receptor (TcR) gamma/delta-bearing cells in host-defense against Listeria monocytogenes, we analyzed the sequential appearance of gamma/delta and alpha/beta T cell in the peritoneal exudate cells (PEC) during an i.p. infection with sublethal dose (2 X 10(3) of viable Listeria organisms in mice. The PEC on day 1 after the infection consisted of 48% macrophages and 50% lymphocytes, most of which were surface IgM+ (B) cells. The number of PEC increased to the maximal level by day 3. The PEC at this stage contained an appreciable number of CD3+ T cells in addition to a large number of macrophages. Of the CD3+ cells, the proportion of CD4- CD8- cells, most of which expressed no TcR alpha/beta, increased to the maximal level on day 3 after the infection. In correlation with an increased number of CD3+ CD4- CD8- TcR alpha/beta- cells, high level of TcR gamma/delta chain gene messages was detected in the nonadherent population of the PEC on this stage. On the other hand, the PEC on day 8 contained an increased number of CD4+ CD8- and CD4- CD8+ cells which expressed TcR alpha/beta chain on their surface. These results suggest that the gamma/delta T cells precede the alpha/beta T cells in appearance during listerial infection. The gamma/delta T cells may be involved at the first line of the host-defense against Listeria.

Animals↗
PubMed1983

[The antibacterial activity of new cephem antibiotics against clinical isolates. A comparison of the antibacterial activity of cefotaxime with 6 other antibiotics].

During the period from May through July 1981, a comparative study was carried out on the antibacterial activities of cefotaxime (CTX) and ceftizoxime (CZX), cefoperazone (CPZ), latamoxef (LMOX), cefotiam (CTM), cefmetazole (CMZ) and cefazolin (CEZ). CTX and these other cephem antibiotics were tested against fresh clinical isolates which had been obtained from clinical materials by the laboratories of 14 participating medical institutions. 1. The clinical isolates were obtained from various clinical materials in the following decreasing order: urine, sputum and pus/discharge; 85.7% of the isolates came from these materials. 2. Concerning the sources of each species of clinical isolates, it was found that P. aeruginosa was isolated from the greatest number -9- of different clinical materials. This was followed by E. coli and E. cloacae, each isolated from 8 different clinical materials, and C. freundii and E. aerogenes, each found in 7 different clinical materials. 3. In relation to S. pyogenes, S. agalactiae and S. pneumoniae, CTX showed the best antibacterial activity; the second most potent antibiotic was CZX. CMZ and LMOX were found to show relatively high MIC values for those species. Against S. aureus, CEZ showed the best antibacterial activity, but 3 resistant strains had MICs of greater than 100 micrograms/ml. 4. With regard to Gram-negative bacteria, CTX and CZX showed the best antibacterial activities for all of the species, except for P. aeruginosa. These were followed, in order, by LMOX and CPZ. Compared with these 4 antibiotics, CTM, CMZ and CEZ were found to have inferior antibacterial activities against these bacteria. In relation to P. aeruginosa, the peak of the MIC distribution for CPZ was 6.25 micrograms/ml, and this was the best antibacterial activity detected with the various antibiotics tested. This was followed by CTX (25 micrograms/ml) LMOX (25 micrograms/ml) and CZX (50 micrograms/ml). CTM had an MIC of 100 micrograms/ml for 1 strain, and MICs of greater than 100 micrograms/ml for all of the other strains of P. aeruginosa, indicating them to be resistant to this antibiotic. All of the strains were resistant to CMZ and CEZ, showing MICs of greater than 100 micrograms/ml. 5. For each of the tested antibiotics, no correlation was found between the MIC and the serogroup for either P. aeruginosa or S. marcescens.

Bacteria↗
PubMed1983

[Pharmacological evaluation of an ampicillin suppository (KS-R1) in acute respiratory tract infection in children: a comparison with an oral form of ampicillin].

A comparative well-controlled study was performed to evaluate the efficacy and tolerability of ampicillin rectal suppository (KS-R1) compared with those of oral form of ampicillin (ABPC) against acute respiratory tract infections in pediatric field. KS-R1 at the dose of 125 mg X 4/day of ABPC in potency, or the oral form at the same dosage, was given to 166 cases of patients with acute respiratory tract infection due to Streptococcus pyogenes, Streptococcus pneumoniae or Haemophilus influenzae for 7 days, as a rule. The clinical efficacy rates evaluated in 151 cases (KS-R1 group in 77 cases, oral group in 74 cases) on standard criteria of committee members were 88.3% for the KS-R1 group and 86.5% for the oral group, respectively. There was no significant difference between 2 groups. Evaluation by stratification according to the diagnosis showed that the efficacy rates for the KS-R1 group and for the oral group were 87.5% and 85.0% against pharyngitis, 90.5% and 90.0% against tonsillitis and 84.2% and 78.6% against bronchitis, respectively. None of them showed significant difference between 2 groups. The bacteriological effect was evaluated in 55 cases (KS-R1 group in 33 cases, oral group in 22 cases), and disappearance rate was 93.9% for the KS-R1 group and 95.5% for the oral group, showing no significant difference. Side effect including subjective and objective symptoms were strictly evaluated in 163 cases (KS-R1 group in 83 cases, oral group in 80 cases), but the incidence rate which was 22.9% for the KS-R1 group and 23.8% for the oral group showed no significant difference. The above results indicate that against acute respiratory tract infections in pediatric field, KS-R1 possesses clinical efficacy and safety similar to the oral form of ABPC, and that it is a useful suppository.

Acute Disease↗
PubMed1983

[Experimental and clinical evaluation of cefotetan in pediatrics].

The authors have carried out the laboratory and clinical studies of cefotetan (CTT), and obtained the following results. The antibacterial activities of CTT were measured by the plate dilution method against the clinical isolates of S. aureus, E. coli, K. pneumoniae, S. marcescens and Salmonella sp. The susceptibility distribution of S. aureus to CTT was at concentration of 6.25-12.5 micrograms/ml and the peak of that was obtained at 6.25 micrograms/ml with an inoculum size of 10(6) cells/ml. And the peaks of susceptibility distribution of E. coli and K. pneumoniae to CTT were obtained at less than 0.1 microgram/ml respectively, and that of S. marcescens was obtained at 6.25-12.5 micrograms/ml with an inoculum size of 10(6) cells/ml. The growth of all strains of Salmonella sp. was inhibited at concentration of less than 0.1 microgram/ml. As for pharmacokinetic study, CTT was given by intravenous bolus injection and drip infusion for 30 minutes at a single dose of 20 mg/kg. After intravenous bolus injection of 20 mg/kg of CTT, the mean peak serum level was 175.0 +/- 7.0 micrograms/ml at 15 minutes after injection, and half-life time was 3.53 hours. After 30 minutes drip infusion of 20 mg/kg of CTT, the mean serum concentration was 106.0 +/- 6.0 micrograms/ml at end of infusion, half-life time was 2.41 hours. The mean urinary excretion rates were 49.4% and 64.2% up to 8 hours after drip and bolus injection of 20 mg/kg of CTT, respectively. CTT was given 15 cases with bacterial infection. Daily doses of CTT were from 15.0 to 107.0 mg/kg. Clinical results obtained were excellent and good responses in 12 of 15 cases (80.0%). No side effects were obtained except for 2 cases with elevation of GOT and GPT, and 1 case with eosinophilia.

Age Factors↗
PubMed1983

[Experimental and clinical evaluation of cefpiramide in pediatrics].

The authors have carried out the laboratory and clinical studies of cefpiramide (CPM). The results were as follows; The sensitivity was estimated by plate dilution method on 27 strains of S. aureus and P. aeruginosa, 26 strains of E. coli, 25 strains of K. pneumoniae and 13 strains of Proteus sp. isolated from patients. The distribution of S. aureus was 0.78 approximately 6.25 micrograms/ml and the peak of distribution was 1.56 micrograms/ml. The distribution of E. coli was 0.78 approximately 50 micrograms/ml and the peak of distribution was 0.78 and 25 micrograms/ml. The growth of 24% of K. pneumoniae was not inhibited at concentration of more than 50 micrograms/ml. The distribution of Proteus sp. was 6.25 approximately 100 micrograms/ml. The growth of 77.8% of P. aeruginosa was inhibited at concentration of less than 3.13 micrograms/ml. CPM was given by intravenous administration for 5 minutes and drip infusion for 30 minutes at a single dose of 20 mg/kg of CPM to each 2 children respectively. After intravenous administration of CPM, the mean peak serum level was 200.5 +/- 37.5 micrograms/ml at 15 minutes, 44.3 +/- 0.9 micrograms/ml at 6 hours, 19.9 +/- 0.3 micrograms/ml at 12 hours respectively. Half-life time was 4.2 hours. After drip infusion of CPM, the mean peak serum level was 150.5 +/- 14.5 micrograms/ml at end of infusion, 23.6 +/- 3.3 micrograms/ml at 6 hours and 8.2 +/- 2.0 micrograms/ml at 12 hours respectively. Half-life time was 3.8 hours. The mean urinary excretion rate was 23.15%, 28.2% up to 12 hours after intravenous administration and drip infusion respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Age Factors↗