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Biomedical subjects

M Honda

Publications and source records attributed to M Honda.

At least 37 records · Page 2Linked to original sources
PubMed2003

Effects of NRA0045, a novel potent antagonist at dopamine D4, 5-HT2A, and alpha1 adrenaline receptors, and NRA0160, a selective D4 receptor antagonist, on phencyclidine-induced behavior and glutamate release in rats.

RATIONALE: Administration of phencyclidine (PCP) to animals produces abnormal behavior such as hyperlocomotion, stereotyped behavior, and ataxia; this abnormal behavior is only weakly blocked by dopamine D(2) receptor antagonists. This study examined the effects of a novel thiazole derivative, NRA0045 which potently antagonizes not only dopamine D(4) receptors but also 5-HT(2A) and alpha(1) adrenaline receptors, and NRA0160, a selective dopamine D(4) receptor antagonist, on PCP-induced abnormal behavior, and accompanying increases in extracellular levels of glutamate in the medial prefrontal cortex. Furthermore, this study compared the effects of these drugs with those of clozapine and haloperidol. METHODS: To study the effects of NRA-drugs, atypical and typical antipsychotics, we measured locomotor activity with an infra-red sensor, and stereotypy and ataxia on a rating scale. Extracellular glutamate levels were measured by in vivo microdialysis. RESULTS: NRA0045 (1 or 3 mg/kg) or clozapine (1 mg/kg) attenuated hyperlocomotion, stereotypy, and ataxia induced by PCP (7.5 mg/kg) without affecting behavior after saline injection. Although haloperidol (0.1 or 1 mg/kg) attenuated or inhibited PCP-induced behavior, this drug also affected behavior after saline injection. NRA0160 (0.1, 1, or 3 mg/kg) had no effect on behavior induced by PCP or saline. NRA0045 (3 mg/kg), but not NRA0160, inhibited PCP-induced increases in glutamate levels in the medial prefrontal cortex. PCP-induced hyperlocomotion correlated with the PCP-induced increases in glutamate levels in this brain region. CONCLUSIONS: These results suggest that the effects of NRA0045 on PCP-induced abnormal behavior are similar to those of the atypical antipsychotic clozapine. NRA0045 probably attenuates PCP-induced abnormal behavior by inhibiting the PCP-induced increase in glutamate levels in the medial prefrontal cortex; this inhibition may be mediated via the blockade of 5-HT(2A) receptors.

Adrenergic alpha-1 Receptor Antagonists↗
PubMed2003

p34cdc2 expression is an independent indicator for lymph node metastasis in colorectal carcinoma.

PURPOSE: The significance of p34(cdc2) expression in human tumors has not been fully explained. The aim of the current study was to elucidate the clinicopathologic significance of immunohistochemical p34(cdc2) expression in carcinoma of the colon and rectum. METHODS: The immunohistochemical expression of p34(cdc2) was examined in 90 consecutive colorectal tumor cases, and p34(cdc2) expression and the clinicopathologic features of the patients and their tumors were compared. RESULTS: Lymph node metastasis was significantly more frequent in tumors expressing p34(cdc2) (47.8%, 11 of 23 tumors) than in tumors not expressing p34(cdc2) (22.4%, 15 of 67 tumors; P=0.020). Multivariate analysis demonstrated that tumor depth ( P=0.008) and p34(cdc2) expression ( P=0.022) were independently associated with lymph node metastases of colorectal carcinomas. CONCLUSIONS: The immunohistochemical expression of p34(cdc2) is independently associated with lymph node metastasis in colorectal carcinoma.

Aged↗
PubMed2003

Infection of macaques with an R5-tropic SHIV bearing a chimeric envelope carrying subtype E V3 loop among subtype B framework.

To establish simian/human immunodeficiency virus (SHIV) clones bearing a chimeric envelope carrying subtype E V3 loop among subtype B envelope, four subtype E V3 sequences were substituted into SHIV(MD14), a SHIV clone bearing an envelope derived from a CXCR4 (X4)/CCR5 (R5)-dual tropic subtype B HIV-1 strain. SHIV-TH09V3, an only V3-chimera clone capable of replicating in human and macaque peripheral blood mononuclear cells (PBMCs), was propagated in pig-tailed macaque PBMCs and in cynomolgus macaque splenic mononuclear cells. The propagated virus stocks were intravenously inoculated into respective macaque species. SHIV-TH09V3 infected both macaque species as shown by plasma RNA viremia, isolated viruses from PBMCs and plasma, and antibody production against viral proteins. To assess how the substituted V3 sequence affected coreceptor usage, SHIV-TH09V3 stocks propagated in vitro and after isolation from macaques were verified for their corecepor usage by GHOST cells assay. SHIV-TH09V3 maintained R5-tropic phenotype both in vitro and after isolation from macaques, in contrast to the X4/R5-dual tropic SHIV(MD14). This indicates the substituted V3 sequence among the backbone of SHIV(MD14) governs coreceptor usage. Future study of infecting macaques with SHIV-TH09V3 and SHIV(MD14) will focus on differences of the outcome caused by the different V3 sequences in connection with coreceptor usage.

Amino Acid Sequence↗
PubMed2003

Rat costochondral cell characteristics on poly (L-lactide-co-epsilon-caprolactone) scaffolds.

This study was designed to examine the adhesion, proliferation, and morphology of chondrocytes on new scaffolds; and to examine these cells histologically for the ability of the chondrocytes to maintain chondrogenic properties after subcutaneous implantation into nude mice. Both 75:25 poly (L-lactide-co-epsilon-caprolactone) (75PLC) and 50:50 poly (L-lactide-co-epsilon-capro-lactone) scaffold (50PLC) were tested as a scaffold for rat costochondral resting zone chondrocytes in comparison with a type I collagen sponge scaffold (collagen scaffold). Both of the poly (L-lactide-co-epsilon-caprolactone) scaffolds (75PLC and 50PLC) were coated with type I collagen solution and the effects of the collagen coat (hybrid-PLC) were also examined. The hybrid-75PLC bound the same number of cells as the collagen scaffold, whereas the 75PLC and the 50PLC bound 60% and 50% fewer cells than the collagen scaffold, respectively. The cell growth on the scaffolds progressed with culture time in all scaffolds. Cell morphology was assessed by scanning electron microscopy for differences in the structure of cellular interaction. Chondrocytes on every scaffold maintained a spherical shape. The hybrid-PLCs were superior to the PLCs with respect to the number of cells attached. The PLCs had an advantageous degradation characteristic in that they retained their original shape better than the collagen scaffold. Additionally, in the PLCs seeded, the cells retained their integrity 4 weeks after implantation, although the volume of collagen scaffold decreased by 50%.

Animals↗
PubMed2003

Unrelated bone marrow transplantation for Epstein-Barr virus-associated T/NK-cell lymphoproliferative disease.

Epstein-Barr virus (EBV)-associated T/NK-cell lymphoproliferative disease (LPD) has been linked to several different disorders, including chronic active EBV infection, EBV-associated hemophagocytic syndrome, hypersensitivity to mosquito bites, hydroa vacciniforme, aggressive NK-cell leukemia, and nasal/nasal-type NK-cell lymphoma. In most instances, these disorders are refractory to conventional treatments and have a poor prognosis. Here, we report a new treatment strategy for EBV-associated T/NK-cell LPD, consisting of immunochemotherapy, intensive combination chemotherapy, and stem cell transplantation. The five patients studied, two with T-cell and three with NK-cell LPD, lacked a human leukocyte antigen-matched, related donor, and therefore received bone marrow grafts from HLA-matched, unrelated donors. The preconditioning regimen consisted of total-body irradiation (12 Gy), etoposide (900 mg/m(2)), and cyclophosphamide (120 mg/kg) or melphalan (210 mg/m(2)). All patients had residual LPD by a quantitative PCR technique prior to transplantation. After unrelated bone marrow transplantation (UBMT), four of the five patients remain in continuous complete remission at a median of 19 months, without detectable EBV-DNA in peripheral blood. Thus, UBMT appears to be a reasonable option for the treatment of patients with EBV-associated T/NK-cell LPD. Detection of EBV-DNA by PCR offers an important tool for assessing minimal residual disease in patients with EBV-associated T/NK-cell LPD.

Adolescent↗
PubMed2003

A case of galactosialidosis.

Galactosialidosis is a lysosomal storage disease associated with a combined deficiency of beta-galactosidase and neuraminidase, caused by a defect of another lysosomal protein, the protective protein. Three subtypes are recognized: the early infantile form, the late infantile form and the juvenile/adult form. We saw a patient with galactosialidosis of the juvenile/adult form, a 51-year-old Japanese man with angiokeratomas on both elbows and knees, myoclonus, ataxia, mental retardation and macular cherry-red spots. An electron-microscopic study of a skin biopsy showed membrane-limited vacuoles in the cytoplasm of the endothelial cells, pericytes and fibroblasts. Assays of enzymatic activity in cultured fibroblasts showed a marked decrease in both beta-galactosidase and neuraminidase (sialidase). The substance contained in the cytoplasmic vacuoles appears to be glycoproteins with sialic acid, which is a terminal glycosyl residue, because the cytoplasm of the endothelial cells of the vessels and pericytes are stained by the Limax flavus agglutinin, a lectin that binds specifically with sialic acid. This technology may be useful for easy investigation of the distribution of the accumulation of such substances in the central nervous system.

Angiokeratoma↗
PubMed2002

Effect of MS-153 on the development of behavioral sensitization to locomotion- and ataxia-inducing effects of phencyclidine.

RATIONALE: Repeated administration of phencyclidine (PCP) produces behavioral sensitization to PCP. Although the precise mechanism is unknown, glutamatergic neurotransmission seems to play an important role in the development of sensitization. OBJECTIVES: The present study examined whether a novel compound, MS-153 (( R)-(-)-5-methyl-1-nicotinyl-2-pyrazoline), which has an ability to enhance glutamate uptake and inhibit glutamate release, would block the development of behavioral sensitization to PCP. METHODS: For studying effects of MS-153, locomotor activity was measured by an infrared sensor and ataxia was measured by a rating scale. RESULTS: MS-153 (10 and 100 mg/kg) enhanced locomotion and ataxia induced by a single injection of PCP (7.5 mg/kg). Repeated administration of PCP (20 mg/kg, once in every day, for 5 days) developed sensitization to locomotion- and ataxia-inducing effects of PCP (7.5 mg/kg). MS-153 given 60 min and 120 min later of every PCP treatment blocked the development of behavioral sensitization to both locomotion- and ataxia-inducing effects of PCP. Co-administration of MS-153 with repeated saline treatment did not produce hypersensitivity to PCP. CONCLUSIONS: These results suggest that the attenuation of glutamatergic neural transmission enhances acute effects of PCP, in contrast, blocks the behavioral sensitization developed by repeated PCP treatment. Therefore, glutamatergic neural transmission plays an important role in the development of behavioral sensitization to PCP.

Animals↗
PubMed2002

Impact of calcium antagonists on bleeding time in patients with chronic renal failure.

Haemorrhagic diathesis develops in chronic renal failure, in which calcium antagonists are used widely as antihypertensive agents. Although calcium antagonists are reported to impair platelet function, it has not been examined whether calcium antagonists alter bleeding time. The present study was conducted to clarify whether calcium antagonists affect bleeding time in chronic renal failure. Patients with chronic renal failure without and with calcium antagonists were enrolled (n = 156), and bleeding time (Ivy's method) as well as blood parameters (BUN, creatinine, platelet counts, and haemoglobin) were compared in patients with normal and prolonged bleeding time. Among patients not taking calcium antagonists (n = 34), three cases manifested prolonged bleeding time, whereas abnormal bleeding time was observed in 31 patients out of 122. Positive correlations were observed between bleeding time and BUN in both calcium antagonist-untreated (r = 0.46) and -treated groups (r = 0.25). The odds ratio for prolongation of bleeding time in patients taking calcium antagonists was 3.52 (95% CI, 1.01-12.33). In 12 calcium antagonist-treated patients with prolonged bleeding time, the withdrawal of calcium antagonists markedly shortened bleeding time (from 11.3 +/- 0.8 to 5.4 +/- 0.8 min, P < 0.05, n = 12). In contrast, in the additional group (n = 9), the continued treatment with calcium antagonists had no effect on bleeding time (from 11.7 +/- 0.9 to 10.0 +/- 1.0 min). Despite the inhibitory effect of calcium antagonists on bleeding time, no clinically serious events associated with haemorrhagic diathesis developed. In conclusion, calcium antagonists prolong bleeding time in patients with chronic renal failure. The subclinical (laboratory) effect of calcium antagonists however is not necessarily associated with haemorrhagic events of clinical significance.

Aged↗
PubMed2002

The rho/rho-kinase pathway is involved in the progression of testicular germ cell tumour.

OBJECTIVE: To clarify the role of one of the downstream effectors of Rho (Rho-kinase) in testicular germ cell tumour (GCT) by quantifying mRNA expression for Rho-kinase in patients with this disease. MATERIALS AND METHODS: The mRNA levels of the RhoA and Rho-kinase genes were analysed in surgical specimens of testicular GCT tissues from 57 consecutive Japanese patients, and in the corresponding non-tumour tissue originating from the same patient, using the polymerase chain reaction after reverse transcription. The expression levels of these genes were compared between the tissues and the relationship between their expression levels evaluated within tumours and with tumour stage. The difference in the expression levels of the mRNAs of RhoA and Rho-kinase genes were also assessed between tumours that were seminoma only and mixed tumours of seminoma and nonseminoma. RESULTS: RhoA and Rho-kinase mRNAs were more abundant in tumour tissue than in non-tumour tissue (P < 0.01 and < 0.05, respectively). High RhoA and Rho-kinase mRNA expressions were related to tumour stage (P < 0.05 and < 0.01, respectively). The mRNA levels of RhoA and Rho-kinase in mixed tumours were higher than in tumours with seminoma only (P < 0.01 and < 0.05, respectively). There was a positive relationship between expression levels of mRNAs of RhoA and Rho-kinase in tumour tissues (P < 0.001). CONCLUSIONS: These findings suggest that the RhoA/Rho-kinase pathway is involved in the progression of testicular GCT. This pathway might be a molecular target for new treatment strategies for this disease.

Adolescent↗
PubMed2002

Abnormal cortical mechanisms of voluntary muscle relaxation in patients with writer's cramp: an fMRI study.

Although it is hypothesized that there is abnormal motor inhibition in patients with dystonia, the question remains as to whether the mechanism related to motor inhibition is specifically impaired. The objective of the present study was to clarify the possible abnormalities of the mechanisms underlying voluntary muscle relaxation during motor preparation and execution in patients with writer's cramp, using event-related functional MRI. Eight patients with writer's cramp and 12 age-matched control subjects participated in the study. Two motor tasks were employed as an experimental paradigm. In the relaxation task, subjects were asked to hold their right wrist in the horizontal plane by maintaining moderate contraction of wrist extensor muscles in the premotor phase; they relaxed those muscles voluntarily just once during each fMRI scanning session. In the contraction task, subjects extended the right wrist voluntarily from the same premotor state as for the relaxation task. Five axial images covering the primary sensorimotor cortex (SMC) and supplementary motor area (SMA) were obtained once every second. Activated volumes in the left SMC and the SMA were significantly reduced in patients for both muscle relaxation and contraction tasks. These data suggest that there is impaired activation in both SMC and SMA in voluntary muscle relaxation and contraction in patients with writer's cramp. This implies that abnormalities of both inhibitory and excitatory mechanisms in motor cortices might play a role in the pathophysiology of focal dystonia.

Adult↗
PubMed2002

Tissue engineering of complex tooth structures on biodegradable polymer scaffolds.

Tooth loss due to periodontal disease, dental caries, trauma, or a variety of genetic disorders continues to affect most adults adversely at some time in their lives. A biological tooth substitute that could replace lost teeth would provide a vital alternative to currently available clinical treatments. To pursue this goal, we dissociated porcine third molar tooth buds into single-cell suspensions and seeded them onto biodegradable polymers. After growing in rat hosts for 20 to 30 weeks, recognizable tooth structures formed that contained dentin, odontoblasts, a well-defined pulp chamber, putative Hertwig's root sheath epithelia, putative cementoblasts, and a morphologically correct enamel organ containing fully formed enamel. Our results demonstrate the first successful generation of tooth crowns from dissociated tooth tissues that contain both dentin and enamel, and suggest the presence of epithelial and mesenchymal dental stem cells in porcine third molar tissues.

Absorbable Implants↗
PubMed2001

Cross-clade neutralizing antibody production against human immunodeficiency virus type 1 clade E and B' strains by recombinant Mycobacterium bovis BCG-based candidate vaccine.

The recombinant Mycobacterium bovis BCG (rBCG) vector-based vaccine secreting the V3 principal neutralizing epitope of human immunodeficiency virus type 1 (HIV-1) Japanese strain was reported to induce both humoral and cellular immune responses effectively [Proc. Natl. Acad. Sci. USA. 92 (1995) 10693]. The antigen-secreting rBCG system was applied to the V3 epitope of clade E HIV-1 in this study. The V3 sequence of 19 amino acids (aa) and 15aa fused with mycobacterial alpha-antigen was not secreted while 12aa and 11aa sequences were successfully secreted from BCG cells. Serum IgG from guinea pig which was immunized with 12aa epitope-secreting recombinant BCG neutralized the WHO reference strain as well as primary field isolates of clade E virus. The serum IgG could also neutralize Thai B (clade B') strains which possessed a conserved GPGQ motif in their V3 sequences. These data suggest that the rBCG construct secreting the 12aa epitope is implicated in the development of a prophylactic vaccine in Thailand in which both clade E and B' viruses are prevalent.

AIDS Vaccines↗
PubMed2001

Catecholamines and opioid peptides increase in plasma in humans during possession trances.

Naturally induced possession trances have been observed in healthy people of many societies. The neurophysiological basis of this phenomenon remains unknown, however, because of the difficulty in accessing subjects in trances due to their sacred context. In the present study, we measured the plasma levels of several neuroactive substances from subjects exhibiting or lacking possession trance characteristics during Balinese dedicatory dramas under natural conditions. The trance group exhibited significant increases in plasma concentrations of noradrenaline, dopamine and beta-endorphin, compared with controls who performed the same actions as the trance group. The present finding suggests that catecholamines and opioid peptides are involved in possession trances.

Adult↗
PubMed2001

HIV mucosal vaccine: nasal immunization with rBCG-V3J1 induces a long term V3J1 peptide-specific neutralizing immunity in Th1- and Th2-deficient conditions.

In the vaccine strategy against HIV, bacillus Calmette-Guérin (BCG), a live attenuated strain of Mycobacterium bovis, is considered to be one of potential vectors for mucosal delivery of vaccine Ag. We analyzed the induction of the Ag-specific Ab response by nasal immunization with recombinant BCG vector-based vaccine (rBCG-V3J1) that can secrete the V3 principal neutralizing epitope of HIV. Mice were nasally immunized with rBCG-V3J1 (10 microg) three times at weekly intervals. Four weeks after the initial immunization, high titers of V3J1-specific IgG Abs were seen in serum. These high levels of HIV-specific serum IgG responses were maintained for >12 mo following nasal immunization without any booster immunization. V3J1-specific IgG-producing cells were detected in mononuclear cells isolated from spleen, nasal cavity, and salivary gland of the nasally vaccinated mice. Nasal rBCG-V3J1 also induced high levels of prolonged HIV-specific serum IgG responses in Th1 (IFN-gamma(-/-))- or Th2 (IL-4(-/-))-immunodeficient mice. Further, IgG3 was highest among V3 peptide-specific IgG subclass Ab responses in these immunodeficient mice as well as in wild-type mice. In addition, this Ag-specific serum IgG Abs induced by nasal immunization with rBCG-V3J1 possessed the ability to neutralize clinical isolate of HIV in vitro. These results suggested that the nasal rBCG-V3J1 system might be used as a therapeutic vaccine in addition to a prophylaxis vaccine for the control of AIDS.

AIDS Vaccines↗
PubMed2001

TGF-beta-producing CD4+ mediastinal lymph node cells obtained from mice tracheally tolerized to ovalbumin (OVA) suppress both Th1- and Th2-induced cutaneous inflammatory responses to OVA by different mechanisms.

Advances in the treatment of allergic disorders require elucidation of the autoregulatory immune systems induced in averting detrimental inflammatory responses against invading foreign Ags. We previously reported that excessive Ags intruding through the airway mucosa induce a subset of regulatory CD4+ T cells secreting TGF-beta in the regional mediastinal lymph nodes (MLNs), which inhibits Th2 cells and subsequent eosinophilic inflammation in the trachea. In the present experiments we examined whether and in what mechanisms TGF-beta-secreting CD4+ T cells in the MLNs regulate Th cell-mediated skin inflammation using a previously established murine model. Th1 or Th2 cells injected s.c. into ear lobes of naive mice induced swelling, whereas the concomitant local injection of MLN cells suppressed the inflammation. The suppressor activities of MLN cells were markedly neutralized by anti-TGF-beta mAb and were mimicked by rTGF-beta. The MLN cell- and rTGF-beta-induced inhibition was reversed by anti-IL-10 mAb significantly in Th1-induced inflammation and only partially in Th2-induced inflammation. rIL-10 reduced Th-induced ear swelling, although higher doses of rIL-10 were required in Th2-induced one. Thus, allergen-specific TGF-beta-producing CD4+ T cells induced in the respiratory tract controlled cutaneous inflammatory responses by Th1 or Th2 cells either directly by TGF-beta or indirectly through IL-10 induction. From a clinical standpoint, these observations might explain the mechanism of spontaneous regression in some patients with atopic dermatitis, which exhibits both Th1- and Th2-mediated skin inflammation in response to airborne protein Ags.

Animals↗
PubMed2001

ABO-incompatible living-donor kidney transplantation in children.

BACKGROUND: Due to a severe shortage of suitable cadaveric allografts for children awaiting kidney transplants, we have performed a series of ABO-incompatible living kidney transplantations (LKT) at our institution. METHODS: Between July 1989 and March 2000, 16 pediatric patients (3 female, 13 male) underwent ABO-incompatible LKT. The mean age at transplantation was 10.9+/-4.3 years (range 5.1-15.0 years). The donor to recipient ABO blood antigen incompatibility was as follows: A1-->O, 5 patients; B-->O, 6 patients; A1B-->B, 2 patients; and A1B -->B, A1-->B, or B-->A1, 1 patient each. The median pretransplantation anti-A1 titers of eight A-incompatible recipients were 1:128 (IgM, range 1:16 to 1:512) and 1:32 (IgG, range 1:2 to 1:128). Median anti-B titers of seven B-incompatible recipients were 1:32 (IgM, range 1:4 to 1:128) and 1:8 (IgG, range 1:2 to 1:64). All patients received three or four sessions of plasmapheresis (PP) and/or immunoadsorption (IA) to remove the anti-A and/or anti-B antibodies before transplantation. Immunosuppression initially consisted of cyclosporine, methylprednisolone, cyclophosphamide, and antilymphocyte globulin. Splenectomy was performed on all recipients at the time of transplantation. RESULTS: The patients were followed for 6 to 122 months with a mean follow-up of 63 months. All 16 recipients who underwent ABO-incompatible LKT achieved a pretransplant isoagglutinin titer less than 1:8 with 3-4 sessions of PP/IA treatment. Of 16 patients, 10 patients had rebound increase in their IgM and/or IgG anti-A/B titers to greater than 1:64 or predepletion levels within 10 days posttransplantation. In addition, nine patients developed renal dysfunction in association with the rebound increase in their anti-A/B. One patient lost his graft because of uncontrolled delayed hyperacute rejection, whereas eight other recipients recovered completely with pulse steroids and PP/IA therapy. After the third week posttransplant, there was no correlation between the occurrence of AR and their isoagglutinin titers. Moreover, no antibody-mediated rejection was observed, even in recipients with continued high titer anti-A and/or anti-B antibodies. Patient survival is 100% to date. The actuarial 1-year and 5-year graft survival rates are 87% and 85%, respectively. No fatal infectious complications occurred despite the combination of splenectomy and immunosuppressive drugs. CONCLUSIONS: We have demonstrated that with adequate pre- and posttransplant management, successful kidney transplantation across the ABO barrier is possible in the pediatric population. "Accommodation" of the allografts occurred within 2 weeks of transplantation. Subsequently, the long-term graft outcome of ABO-incompatible LKT was comparable to that of ABO-compatible LKT.

ABO Blood-Group System↗