Kazuhiko Suzuki

The University of Tokyo, Edo, Tōkyō, Japan

Are you Kazuhiko Suzuki?

Claim your profile

Publications (21)35.24 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Subcutaneous and intraperitoneal administrations of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) induce selective dopaminergic (DA-ergic) neuronal death in many animal species. After passing through the blood-brain barrier (BBB), MPTP is converted to 1-methy-4-phenylpiridinium (MPP(+)) by astrocytic monoamine oxidase-B (MAO-B). MPP(+) then induces the dopaminergic neuronal death. In mice, marked strain differences in the susceptibility to MPTP-injection have been reported. To clarify which factor(s) cause the strain differences, MPTP or MPP(+) was intracerebroventricularly (icv) injected into adult C57BL/6 (highly susceptible to MPTP) and BALB/c (resistant to MPTP) mice. The brain tissues including the striatum and substantia nigra pars compacta (SNpc) were examined immunohistochemically using an antibody to tyrosine hydrocyrase (TH). MPP(+)-injected C57BL/6 mice showed a significant decrease in TH-immunopositive areas in the striatum at Day 3 post injection (p<0.01), and TH-positive cells in the SNpc at Days 1 and 3 (p<0.01), respectively, compared to saline-injected control mice. In addition, MPP(+)-injected BALB/c mice showed a significant decrease in TH-positive areas in the striatum at Days 1 and 3, and SNpc TH-positive cells in the SNpc at Day 3, respectively (p<0.05). However, the decrease rates in the BALB/c mice were lower than that in C57BL/6 mice. MPTP-injected C57BL/6 mice, however, showed no lesions in the striatum and SNpc at Days 1 and 7 after icv injection. All the present findings indicate that factors other than MAO-B can influence the strain susceptibility between C57BL/6 and BALB/c mice after the conversion from MPTP to MPP(+).
    Experimental and toxicologic pathology: official journal of the Gesellschaft fur Toxikologische Pathologie 08/2011; 65(1-2). DOI:10.1016/j.etp.2011.07.004 · 2.01 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Intraperitoneal 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) administration induces apoptosis of subventricular zone (SVZ) doublecortin (Dcx)-positive neural progenitor cells (migrating neuroblasts, A cells). Actually, a metabolite of MPTP, 1-methy-4-phenylpiridinium (MPP(+)), is responsible for neural progenitor cell toxicity. In the present study, to examine whether the MPTP-induced SVZ cell apoptosis is caused directly by MPP(+) metabolized through monoamine oxidase B (MAO-B), MPTP or MPP(+) was intracerebroventricularly (icv) injected into C57BL/6 mice. At Day 1 postinjection, many terminal deoxynucleotidyl transferase-mediated dUTP endlabeling (TUNEL)-positive cells were observed in the SVZ of both low (36μg) and high (162μg) dose MPTP- and MPP(+)-injected mice. The number of Dcx-positive A cells showed a significant decrease following high dose of MPTP- or MPP(+)-injection on Days 1 and 3, respectively, whereas that of EGFR-positive C cells showed no change in mice with any treatment. In addition, prior icv injection of a MAO-B inhibitor, R(-)-deprenyl (deprenyl), inhibited MPTP-induced apoptosis, but not MPP(+)-induced apoptosis. MAO-B- and GFAP-double positive cells were detected in the ependyma and SVZ in all mice. It is revealed from these results that icv injection of MPTP induces apoptosis of neural progenitor cells (A cells) in the SVZ via MPP(+) toxicity. In addition, it is suggested that the conversion from MPTP to MPP(+) is caused mainly by MAO-B located in ependymal cells and GFAP-positive cells in the SVZ.
    Experimental and toxicologic pathology: official journal of the Gesellschaft fur Toxikologische Pathologie 02/2011; 64(7-8):761-5. DOI:10.1016/j.etp.2011.01.013 · 2.01 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Subdural histiocytic sarcomas from 15 dogs (mean age 7.8 years) were histopathologically examined. Among the 15 dogs, there was a marked breed predominance (toward Pembroke Welsh Corgi dogs, 47%), but no gender predilection. Focal solitary subdural masses were detected in the cerebrum (12 cases) and spinal cord (1 case), whereas diffuse infiltrative lesions were observed in the cerebral leptomeninges in 2 cases. All neoplastic lesions had common histological features characterized by the proliferation of pleomorphic histiocytic cells combined with various inflammatory reactions. Multinucleated giant cells, phagocytosis, and atypical mitotic figures in the neoplastic cells were commonly observed. Most of the pleomorphic neoplastic cells in the present cases were immunopositive for monocytic, histiocytic, or both markers, such as human leukocyte antigen (HLA)-DR, ionized calcium-binding adaptor molecule 1 (Iba1), cluster of differentiation (CD)163, and CD204, except for the neoplastic cells in 2 focal and 2 diffuse histiocytic sarcomas. The findings suggest that differences in cell origin, molecular expression, or both patterns are responsible for the distribution patterns of canine subdural histiocytic sarcomas.
    Journal of veterinary diagnostic investigation: official publication of the American Association of Veterinary Laboratory Diagnosticians, Inc 01/2011; 23(1):127-32. DOI:10.1177/104063871102300123 · 1.23 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The paper describes clinical and pathological features of Alexander's disease (AD)-like disorder in a 1 year and 8 months old French bulldog. Clinically, the dog exhibited megaesophagus, emaciation and weakness without any specific neurological symptoms. The dog died of aspiration pneumonia. On the gross observation of formalin-fixed brain, discolored foci were observed in the white matter of the cerebellum and brain stem. Histologically, numerous Rothenthal fibers and hypertrophic astrocytes were distributed especially in the perivascular, subependymal and subpial area of both the cerebrum and cerebellum. The Rosenthal fibers were intensely immunopositive for GFAP and ubiquitin. Demyelination of the white matter was occasionally found in the brain stem. The present case is likely to be categorized in the adult form of AD, though previous AD-like cases in dogs were in the juvenile form.
    Journal of Veterinary Medical Science 10/2010; 72(10):1387-90. DOI:10.1292/jvms.10-0085 · 0.88 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: A cDNA microarray analysis was conducted to examine hepatic gene expression profiles in pregnant and lactating F344 rats compared to a virgin control group using an Affymetrix GeneChip system. Of the approximately 16000 gene transcripts interrogated, more than 1000 were significantly modified in their expression when detected either in late pregnancy (19 days of gestation, GD 19, 513 genes upregulated and 579 downregulated) or on the day of delivery (postpartum 0 day, PPD 0, 497 upregulated and 733 downregulated). Particular interest was paid to the gene expression of drug-metabolizing enzymes (DMEs) and nuclear receptors (NRs). Though the expression of a few genes, those for CYP7A1, CYP51 and Sultx3, increased, the expression of a number of genes encoding DMEs (Phase I and Phase II) and NRs decreased during pregnancy and lactation. Changes in the expression of 9 genes encoding DMEs and NRs were confirmed by quantitative real-time PCR. For all 9 genes tested, overall, the results of the microarray and real-time PCR analyses were in agreement. This is the first application of a microarray analysis to the expression profiling of genes encoding DMEs and NRs in the liver of pregnant and lactating rats. When combined with other studies, the present study may provide a basis for investigating the mechanism of toxicity of environmental or other nonphysiologic chemicals to the fetus and mother and drug safety during pregnancy and lactation.
    Experimental and Molecular Pathology 01/2008; 83(3):428-34. DOI:10.1016/j.yexmp.2006.05.002 · 2.88 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The changes in susceptibility of neurons to the D variant of EMC virus (EMC-D) (10(6) PFU/well) were investigated in developing hippocampal primary cultures from postnatal days of 1, 7, and 56 Fischer 344 rats (P1, P7, and P56) for up to 12 h after infection (12 HAI). The virus titer of primary culture neurons increased at 1 HAI, decreased at 2 HAI, increased at 3 HAI, peaked at 8 HAI, and decreased at 12 HAI in all age groups. The titers at 1 and 8 HAI were lowest in P56 cultures. The virus titer of neurons was always higher than that of culture media, especially at 1 HAI, in P1 cultures, whereas the former was lower than the latter from 2 to 3 HAI in P7 cultures and from 2 to 4 HAI in P56 cultures, respectively. Signals of viral RNA detected by in situ hybridization were first observed in the peripheral cytoplasm of neurons at 1 HAI in P1 and P7 cultures and at 4 HAI in P56 cultures, respectively. The signals spread to a large or whole area of cytoplasm and also to processes thereafter. The number of viral RNA-positive neurons and the amount of signals decreased with age. The present results indicated that the susceptibility of primary culture neurons to EMC-D decreased with age but viral replication still occurred in P56 cultures.
    Experimental and Molecular Pathology 11/2003; 75(2):160-4. DOI:10.1016/S0014-4800(03)00068-6 · 2.88 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: We investigated the effects of daily injection of tacrolimus (FK), an immunosuppressor, or dexamethasone (Dx), an antiinflammatory agent, on renal tubulointerstitial fibrosis in mercuric chloride-treated Brown Norway rats. The tubular lesions observed after one time injection of mercuric chloride were reduced in FK-treatment group, but not in Dx-treatment group. Moreover, FK reduced infiltration of mononuclear cells, especially macrophages, and proliferation of myofibroblasts in renal intestitium and also inhibited renal interstitial fibrosis through the reduction of the expressions of fibrosis-related factors, i.e. plasminogen activator inhibitor-1 and transforming growth factor-beta1. On the other hand, Dx reduced lymphocyte infiltraton, but did not inhibit macrophage infiltration. In addition, Dx did not suppress myofibroblast profiferation, upregulation of fibrosis-related factors, and interstitial fibrosis. From these findings, it is suggested that FK may inhibit renal interstitial fibrosis through inhibition of macrophage infiltration, and that macrophages and myofibroblasts are very important fibrogenic factors in the development of mercuric chloride-induced renal tubulointerstitial fibrosis in BN rats.
    Experimental and Toxicologic Pathology 10/2003; 55(2-3):197-207. DOI:10.1078/0940-2993-00314 · 2.01 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: We investigated the kinetics of chemokines and their receptors in mercuric chloride-treated brown Norway (BN) rats from the viewpoint of its relation to the development of tubulointerstitial fibrosis with mononuclear cell infiltration. BN rats were injected subcutaneously with 1 mg/kg b.w. of mercuric chloride one or three times. The kidney was examined histopathologically and the kinetics of chemokines and their receptors in the kidney were also examined using immunohistochemistry and RT-PCR. As a result, mercuric chloride induced tubular injury and subsequent tubulointerstitial fibrosis accompanied with mononuclear cell infiltration. Macrophages were the most predominant population of infiltrating cells and lymphocytes were the next. In the lesions, the expression of MCP-1 mRNA was most prominently elevated, and those of RANTES and IP-10 mRNAs also increased, and their proteins were localized in tubular epithelium. As to their receptors, the levels of CCR1, CCR2, and CXCR3 mRNAs showed significant and prominent elevations, CCR5 mRNA also increased moderately, and their receptor protein-expressing cells also increased. The present findings suggest that MCP-1, RANTES, and IP-10 may participate in the pathogenesis of mercuric chloride-induced tubulointerstitial fibrosis with mononuclear cell infiltration, via CCR2, CCR1 or CCR5, and CXCR3, respectively.
    Experimental and Molecular Pathology 09/2003; 75(1):58-67. DOI:10.1016/S0014-4800(03)00028-5 · 2.88 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Mini rats (Jcl: WistarTGN(ARGHGEN) 1Nts) (MRs) are Wistar rat (WR)-derived transgenic rats in which the expression of growth hormone (GH) gene is suppressed under the presence of antisense RNA transgene. In order to evaluate the effects of GH-deficiency on the acute injury by external stimuli, the dorsal skin responses to a single topical application with 20% hydrogen peroxide (HPO), one of the environmental oxidative stressors, were histologically compared between male MRs and WRs of 8 weeks old, whose hair cycle was under the telogen phase. As a result, formation of granulation tissues, reepithelialization and regrowth of hair follicles were delayed in MRs compared with WRs. While hair follicles of MRs of this age are under a long-lasting telogen phase after their 2nd cycle, a new hair cycle started not only in the HPO-applied area but also in the solvent-applied area with a little time lag. These findings suggest that GH-deficiency may influence the skin responses to the external chemical stimuli.
    Experimental and Toxicologic Pathology 12/2002; 54(3):239-44. DOI:10.1078/0940-2993-00256 · 2.01 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Three sulphur-crested cockatoos (Cacatua galerita) were diagnosed as psittacine beak and feather disease (PBFD). Histopathology of the feather pulp and follicles showed intracytoplasmic botryoid clusters or granular inclusion bodies in epithelial cells and macrophages. Electron microscopy revealed multiple cytoplasmic clusters of electron dense viral particles corresponding to the inclusions. PBFD virus (circovirus) DNA-specific product was detected from formalin-fixed paraffin-embedded feathers by nested polymerase chain reaction (PCR) method.
    Journal of Veterinary Medical Science 07/2002; 64(6):527-9. DOI:10.1292/jvms.64.527 · 0.88 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: A retrospective study for the detection of porcine circovirus 2 (PCV-2) DNA was conducted by nested PCR method in 16 cases of swine post-weaning multisystemic wasting syndrome (PMWS) in Thailand. Histopathology showed characteristic lesions of PMWS and intracytoplasmic viral inclusion bodies in macrophages infiltrating in lymphoid tissues. PCV-2 DNA was detected from formalin-fixed and/or formalin-fixed paraffin-embedded tissues from all pigs with PMWS. The amplified products were digested with Hae III.
    Journal of Veterinary Medical Science 06/2002; 64(5):449-52. DOI:10.1292/jvms.64.449 · 0.88 Impact Factor
  • Kazuhiko Suzuki, Hiroyuki Nakayama, Kunio Doi
    [Show abstract] [Hide abstract]
    ABSTRACT: We investigated the kinetics of matrix metalloproteinases (MMPs) and their regulatory factors mRNAs in the kidneys of mercuric chloride-treated Brown Norway rats. The expression of MMP-1 mRNA remained at lower levels than control, while other MMPs mRNAs were upregulated. The expression of tissue inhibitor of matrix metalloproteinase (TIMP)-1 mRNA showed significant upregulation. On the other hand, the expressions of TIMP-2 and TIMP-3 mRNAs were not significantly changed. In the plasmin-dependent pathway, the expression of plasminogen activator inhibitor (PAI-1) mRNA was continuously increased, while the expression of urokinase-type plasminogen activator (uPA) mRNA was not increased. The signals of TIMP-1 and PAI-1 mRNAs examined by in situ hybridization, were localized in the regenerative epithelial cells of the proximal tubules. In conclusion, these findings suggest that the activity of MMPs may bealtered by MMP-1 downregulation and inhibition of MMP activity by PAl-1 and TIMP-1 generated from tubular epithelial cells.
    Experimental and Toxicologic Pathology 11/2001; 53(5):337-43. DOI:10.1078/0940-2993-00199 · 2.01 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The kinetics of cytokines mRNAs expression was examined in the dorsal skin of Wistar-derived hypotrichotic WBN/ILA-Ht rats topically applied with T-2 toxin. After the application of 10 microl (0.5 microg/microl) of T-2 toxin solution, the total mRNA was obtained from skin biopsies at 3, 6, 12 and 24 hours after treatment (HAT). Reverse transcription-polymerase chain reaction (RT-PCR) was carried out with pairs of oligonucleotide primers corresponding to the cDNA sequences of rat TNF-alpha, IL-1 alpha, IL-1beta, IL-6 and IL-10 cytokines. The level of TNF-alpha mRNA showed marked elevation at 3HAT and decreased toward 24HAT, but it remained significantly higher level even at 24HAT. In addition, the level of IL- 1beta mRNA expression showed a sligth but significant elevation at 3 and 24HAT. On the other hand, no significant differences were observed in other cytokines mRNAs expression between T-2 toxin-treated and control groups througth the observation period. Together with our previous report describing the sequence of epidermal cell apoptosis (Albarenque et al. 1999), the present results suggest that the elevation of TNF-alpha mRNA expression may play an important role in T-2 toxin-induced epidermal cell apoptosis.
    Experimental and Toxicologic Pathology 10/2001; 53(4):271-4. DOI:10.1078/0940-2993-00189 · 2.01 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The expression of apoptosis-related genes mRNAs was examined in the dorsal skin of hypotrichotic WBN/ILA-Ht rats topically applied with T-2 toxin (10 microl of 0.5 microg/microl solution). The total mRNA was obtained from skin biopsy samples from each rat at 3, 6, 12 and 24 hours after T-2 toxin treatment (HAT), and RT-PCR was carried out with pairs of oligonucleotide primers corresponding to the cDNA sequences of rat p53, bcl-2, c-ki-ras, c-fos and c-jun oncogenes. The expression of c-fos mRNA markedly increased at 3 HAT, peaked at 6 HAT, and greatly decreased at 12 HAT. However it maintained a higher level, compared with the control level, even at 24 HAT. Although not prominent, the expression of c-jun mRNA also showed significant elevation from 3 to 12 HAT. On the other hand, there were no changes in the expression of p53, bcl-2 and c-ki-ras mRNAs throughout the observation period. Judging from the present results and our previous report that epidermal cells developed apoptosis at 12 HAT (Histol Histopathol 1999; 14: 337-342), the induction of c-fos and perhaps of c-jun mRNAs may be associated with T-2 toxin-induced epidermal cell apoptosis.
    Experimental and Toxicologic Pathology 03/2001; 52(6):553-6. DOI:10.1016/S0940-2993(01)80016-6 · 2.01 Impact Factor
  • Kazuhiko Suzuki, Hiroyuki Nakayama, Kunio Doi
    [Show abstract] [Hide abstract]
    ABSTRACT: A very rare case of the liver lesion characterized by formation of multinucleated giant hepatocytes with inflammatory cell infiltration were observed in two young (1.5 years and 2 years old) cats bearing thymic malignant lymphoma. Histopathological features of this liver lesion were very similar to giant cell hepatitis (GCH) in human neonates and infants. Therefore, the lesion was diagnosed as feline GCH.
    Journal of Veterinary Medical Science 03/2001; 63(2):199-201. DOI:10.1292/jvms.63.199 · 0.88 Impact Factor
  • Journal of Toxicologic Pathology 01/2001; 14(4). DOI:10.1293/tox.14.299 · 0.94 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Depression of basal cell proliferating activity and subsequent induction of basal cell apoptosis in the epidermis and infiltration of inflammatory cells including mast cells in the dermis were observed in the dorsal skin of hypotrichotic WBN/ILA-Ht rats following the topical application of T-2 toxin in our previous study (ALBARENQUE et al. 1999). In the present study, kinetics of TGF-beta 1 mRNA was investigated using the same experimental system. The level of TGF-beta 1 mRNA of the whole skin tissue measured by competitive RT-PCR method showed a slight elevation from 6 to 12 hours after treatment (HAT) and reached the significantly higher level at 24HAT compared with the control skin. The increase in signals of TGF-beta 1 mRNA detected by in situ hybridization method started at 3HAT in the epidermis and progressed thereafter both in the epidermis and in the dermis. These results suggest that the elevated level of TGF-beta 1 mRNA may have a close relation to the induction of epidermal basal cell apoptosis as well as to the intradermal infiltration of mast cells and fibroblasts following the topical application of T-2 toxin.
    Experimental and Toxicologic Pathology 09/2000; 52(4):297-301. DOI:10.1016/S0940-2993(00)80050-0 · 2.01 Impact Factor
  • Journal of Toxicologic Pathology 01/2000; 13(4):231-236. DOI:10.1293/tox.13.231 · 0.94 Impact Factor
  • Kazuhiko Suzuki, Hiroyuki Nakayama, Kunio Doi
    Journal of Toxicologic Pathology 01/2000; 13(4):213-218. DOI:10.1293/tox.13.213 · 0.94 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Renal tubulointerstitial lesions in mercuric chloride(HgCl2)-treated Brown Norway rats were investigated focusing on the kinetics of transforming growth factor-beta1(TGF-beta1) and extracellular matrix (ECM). Rats were injected with 1 mg/kg b.w. of HgCl2 at days 0, 2, and 4, and 5 rats were killed at days 2, 4, 6, 8, 10, and 20, respectively. TGF-beta1 mRNA expression in the renal cortex measured by competitive RT-PCR method reached a peak at day 6, mildly decreased at days 8 and 10, and increased again toward day 20. Signals of TGF-beta1 mRNA examined by in situ hybridization method were recognized in the regenerative tubular epithelium at day 6, and in both tubular epithelium and infiltrated mononuclear cells at day 20. After tubular injury, strong immunoreactivity to TGF-beta1 protein was found in desquamated tubular epithelial cells. Then, positive staining was found in the regenerative tubular epithelial cells. Later, infiltrated mononuclear cells also became positive for TGF-beta1 protein. In the ECM, deposition of fibronectin was prominent throughout the experimental period. In conclusion, this strongly suggests that TGF-beta1 derived from tubular epithelial cells and some macrophages might be related to the development of renal interstitial fibrosis in HgCl2-treated BN rats.
    International Journal of Experimental Pathology 07/1999; 80(3):125-32. DOI:10.1046/j.1365-2613.1999.00110.x · 2.05 Impact Factor