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T Fukazawa

Publications and source records attributed to T Fukazawa.

At least 55 records · Page 3Linked to original sources
PubMed1999

Expression of CD80 and CD86 on peripheral blood T lymphocytes in patients with systemic lupus erythematosus.

CD80 and CD86 were detected in high amounts on circulating T cells in the peripheral blood of some patients with systemic lupus erythematosus (SLE), using flow cytometry and monoclonal antibodies. Patients with other connective tissue diseases did not have a high percentage of T cells expressing CD80 or CD86 in their peripheral blood. CD80 was expressed mainly on CD4 T cells, whereas CD86 was expressed on CD8 T cells, and these two populations were associated with particular clinical features. These two molecules were expressed on different T-cell populations and might have different roles in the generation and regulation of immune responses. Since high expression of CD86 on T cells was detected much earlier than the appearance of clinical features and a high titer of anti-DNA antibody, it may be a useful parameter for predicting the flare of SLE.

Adult↗
PubMed1999

Overexpression of the p21 sdi1 gene induces senescence-like state in human cancer cells: implication for senescence-directed molecular therapy for cancer.

Normal cells in a culture enter a nondividing state after a finite number of population doubling, which is termed replicative senescence, whereas cancer cells have unlimited proliferative potential and are thought to exhibit an immmortal phenotype by escaping from senescence. The p21 gene (also known as sdi1), which encodes the cyclin-dependent kinase inhibitor, is expressed at high levels in senescent cells and contributes to the growth arrest. To examine if the p21sdi1 gene transfer could induce senescence in human cancer cells, we utilized an adenoviral vector-based expression system and four human cancer cell lines differing in their p53 status. Transient overexpression of p21sdi1 on cancer cells induced quiescence by arresting the cell cycle at the G1 phase and exhibited morphological changes, such as enlarged nuclei as well as a flattened cellular shape, specific to the senescence phenotype. We also showed that p21sdi1-transduced cancer cells expressed beta-galactosidase activity at pH 6.0, which is known to be a marker of senescence. Moreover, the polymerase chain reaction-based assay demonstrated that levels of telomerase activity were significantly lower in p21sdi1-expressing cells compared to parental cancer cells. These observations provide the evidence that p21sdi1 overexpression could induce a senescence-like state and reduce telomerase activity in human cancer cells, suggesting that these novel p21sdi1 functions may have important implications for anticancer therapy.

Adenoviridae↗
PubMed1999

Early carcinoma of the distal second part of the duodenum treated by wedge resection.

A case of early carcinoma of the distal second part of the duodenum, in a 74-year-old man, is presented. Endoscopic retrograde cholangiopancreatography was performed for diagnosis of a common bile duct stone. During this procedure, small elevated lesions were found incidentally in the distal second part of the duodenum, and the histologic examination of a biopsy specimen showed adenocarcinoma. The lesions were removed by wedge resection, and pathologic examination revealed duodenal carcinoma limited to the lamina propria. Although carcinoma of the duodenum, other than of the ampulla of Vater region, is very rare, it is sometimes possible to detect asymptomatic early tumors. However, this requires careful observation of the entire duodenal mucosa, including that of the distal duodenum, at duodenoscopy.

Adenocarcinoma↗
PubMed1999

Persistent infection of hepatitis C virus in the elderly: a clinical and quantitative pathological study of autopsy cases.

AIMS/BACKGROUND: The entire spectrum of persistent infection by hepatitis C virus (HCV) is still unknown. METHODS: A total of 37 autopsy cases, positive with second generation anti-HCV ELISA, were analyzed. The cases comprised 15 males and 22 females, the average ages being 76.5 in males and 81.1 in females. Twenty-one cases were found to be asymptomatic, while 16 were symptomatic. RESULTS: Based on two pathological parameters of hepatic fibrosis and inflammation, the cases were divided into five groups; group A (non-inflammatory group without significant fibrosis; 11 cases), group B (inflammatory group without significant fibrosis; 9 cases), group C (non-inflammatory group with significant fibrosis; 1 case), group D (inflammatory group with significant fibrosis; 11 cases) and group E (undetermined inflammatory index; 5 cases). All cases in group A and seven cases in group B were asymptomatic. Group A included 6 cases with normal liver. All cases in groups C and D were symptomatic. All examined cases of the inflammatory groups were positive for serum HCV-RNA. CONCLUSION: Anti-HCV-positive elderly autopsy patients include many asymptomatic cases. The two pathological parameters of hepatic fibrosis and inflammation can be used to divide the cases into five groups with each group being well correlated with clinical and virological features.

Adult↗
PubMed1999

Pharmacological effects of a novel recombinant hirudin, CX-397, in vivo and in vitro: comparison with recombinant hirudin variant-1, heparin, and argatroban.

The novel recombinant hirudin analog CX-397 was investigated with respect to its pharmacological activity and antithrombin profiles in vivo and in vitro. In three different types of thrombosis models in rats, including stasis and thrombin-induced venous, glass surface-activated arterio-venous shunt, and ferric chloride-induced arterial thrombosis models, CX-397 and rHV-1 elicited potent antithrombotic effects, where the minimum effective doses of rHV-1 tended to be higher than those of CX-397 in the arterio-venous shunt and arterial thrombosis models. The hemorrhagic risk of CX-397 in template bleeding in rats was not higher than that of rHV-1, indicating that CX-397 is superior to rHV-1 for treating the platelet-dominant type of thrombosis. However, no differences were detected between CX-397 and rHV-1 in their effects on in vitro coagulation times and thrombin-induced platelet aggregation, suggesting the possibility that some unknown mechanisms other than simple thrombin inhibition are also involved in their antithrombotic actions.

Amino Acid Sequence↗
PubMed1999

[A clinical trial of acetazolamide for SCA6].

Spinocerebellar ataxia type 6 (SCA 6) is an allelic disorder of episodic ataxia type 2 (EA 2) and is caused by a small CAG repeat expansion in the gene encoding the alpha 1A-voltage-dependent-Ca channel subunit (CACNA 1 A) on chromosome 19p13.1. The disorder starts at adulthood with progressive cerebellar ataxia, and the symptoms often fluctuate at early stage. These clinical features overlap with those of EA 2, which has been known as acetazolamide-responsive ataxia. On this background, we studied the clinical effectiveness of acetazolamide for SCA 6 in 9 consecutive patients. Their clinical severity was serially evaluated by ARS (ataxia rating scale) and gravimetric test, over 32 weeks of oral administration of acetazolamide (250-500 mg/day). Consequently, a significant improvement was observed in ARS and postural sway. Our results indicate that acetazolamide is temporally effective for ameliorating the symptoms of SCA 6. However, its effects for the disease progression need to be examined in more large scales in number and duration.

Acetazolamide↗
PubMed1999

Induction of differentiation-dependent apoptosis in human esophageal squamous cell carcinoma by adenovirus-mediated p21sdi1 gene transfer.

When keratinocytes withdraw from the cell cycle, they migrate from the basal to the superficial layers of the epidermis and undergo morphological and biochemical changes during the process of terminal differentiation. These differentiation features of keratinocytes are known to be altered or reduced in esophageal cancer cells. Therefore, we examined the effects of transferring the cyclin-dependent kinase inhibitor p21sdi1 gene into human esophageal cancer cell lines as well as normal keratinocytes using an adenovirus vector system. Ectopic expression of p21sdi1 protein resulted in cell cycle arrest at the G1 phase and produced morphological changes, such as enlarged nuclei and a flattened cellular shape, changes specific to the differentiated phenotype. The human involucrin protein is a specific product of keratinocyte differentiation, which is selectively expressed in the suprabasal epidermal layers. Western blot analysis and immunohistochemical staining demonstrated that involucrin expression was 3- to 5-fold enhanced by the forced expression of p21sdi1 in esophageal cancer cells, whereas only a mild up-regulation up to 1.2-fold occurred in normal keratinocytes. We also found that exogenous introduction of the p2sdi1 gene transcriptionally activated the upstream promoter function of the involucrin gene. These stimulatory effects on involucrin expression were not observed when another cyclin-dependent kinase inhibitor gene, p16(INK4a), was transduced. Moreover, p21sdi1 expression in esophageal cancer cells transduced with p21sdi1 led to a rapid apoptotic cell death after a transient dormant phase, although keratinocytes transduced with p21sdi1 survived longer by terminally withdrawing from the cell cycle. These results may have an important implication for understanding the biology of differentiation-dependent apoptosis in human esophageal squamous cell carcinoma.

Adenoviruses, Human↗
PubMed1998

Phenotype variation correlates with CAG repeat length in SCA2--a study of 28 Japanese patients.

Spinocerebellar ataxia-2 (SCA2) is an autosomal dominant ataxia caused by an abnormal CAG repeat expansion in a novel gene on chromosome 12q24.1. The size of the mutant allele is unstable during transmission, and correlates inversely with age at onset. We studied eight Japanese SCA2 families, including 28 patients, to assess the effect of repeat length on the phenotype features of SCA2. Frequencies of slow eye movements (SEM), reflex activity, dementia, choreiform movements, and axial tremor correlated significantly with CAG repeat size. Parkinsonism was seen in a man homozygote for SCA2 mutation. The clinical variety of SCA2 is apparently influenced by the size of the mutant allele, as is the case in other CAG repeat disorders.

Adolescent↗
PubMed1998

The significance of oligoclonal bands in multiple sclerosis in Japan: relevance of immunogenetic backgrounds.

We compared clinical and demographic features, MRI findings, and HLA profiles of 57 Japanese patients with multiple sclerosis (MS) between groups with and without oligoclonal IgG bands (OCB) in the cerebrospinal fluid (CSF). Patients with the optic-spinal form of MS (OpS-MS) or acute transverse myelopathy (ATM), which are distinctive and relatively common in Japanese MS, were excluded in this study. The OCB-positive rate was only 56.1% (32/57) among these 57 'conventional' MS patients, of whom clinical features were similar to those of Western MS patients. The demographic features, clinical course, disability, and cerebral abnormalities seen on MRI were similar in the OCB-negative and OCB-positive patient groups. HLA-DR2 antigen, which has been confirmed to be associated with MS in many populations, was more common in the OCB-positive than in the OCB-negative and control groups. Furthermore, DR4 antigen was statistically more common in the OCB-negative patient group. These results raise the possibility that the presence of OCB is related to the immunogenetic background of the patient, and that there may be at least two subpopulations in Japanese patients with 'conventional' MS from the viewpoint of immunogenetics. In one subpopulations, MS is associated with the DR2 antigen, and shows a stronger humoral immune response in the CSF, while in the other MS is associated with DR4, which has a milder humoral response. Further investigations involving more patients are warranted.

Adult↗
PubMed1998

Apoptosis of lymphocytes induced by glucocorticoids and relationship to therapeutic efficacy in patients with systemic lupus erythematosus.

OBJECTIVE: Glucocorticoids (GCs) are the drugs of first choice for treatment of systemic lupus erythematosus (SLE). However, the disease in some patients is resistant to these agents. This study evaluated the possibility of a relationship between response to GC treatment and the rate of apoptosis in vitro, and also analyzed Bcl-2 and Fas expression on peripheral blood mononuclear cells (PBMC) from patients with SLE in relation to GC-induced apoptosis. METHODS: Twenty-seven SLE patients and 13 normal controls were studied. Disease activity scores were determined before and after treatment and used to divide patients into 2 groups: GC-resistant and GC-responsive. Isolated PBMC were stimulated with anti-CD3 monoclonal antibodies, cultured with various concentrations of GC, and analyzed by alamar blue assay to determine the LC50, defined as the concentration of GC lethal to 50% of the cells. We measured the expression of CD4, CD8, Fas, and Bcl-2 by FACStar plus flow cytometry. RESULTS: Lymphocytes in the GC-resistant group of SLE patients showed a significantly lower percentage of GC-induced apoptotic cells than did lymphocytes from the responsive group or from normal controls. The LC50 in the resistant group was significantly higher than that in normal controls or the responsive group. The lymphocytes remaining in the resistant group after GC treatment were mainly CD8+, with a high expression of Bcl-2. There was no significant difference in Fas expression between the GC-responsive and GC-resistant groups. CONCLUSION: Determination of the LC50 may be useful in predicting the efficacy of GC treatment in SLE patients, and may be of use in considering other treatment options. CD8 and Bcl-2 double-positive lymphocytes that are insensitive to the apoptotic effect of GCs may play a role in the resistance to these agents in SLE patients.

Adolescent↗
PubMed1998

SCA6 mutation analysis in a large cohort of the Japanese patients with late-onset pure cerebellar ataxia.

Spinocerebellar ataxia type 6 (SCA6) is caused by small CAG repeat expansion in the gene encoding the alpha1A-voltage-dependent-calcium channel subunit (CACNLIA4) on chromosome 19p13, and is a subgroup of the late-onset pure cerebellar ataxia (ADCA III). To investigate the prevalence of SCA6 in the Japanese, we analyzed this mutation in 23 families and 12 probands with ADCA III. The specificity and stability of the CAG repeat were examined in additional individuals and families with other miscellaneous dominant SCAs. The CAG expansion of SCA6 gene was exclusively observed in 12 of 23 families (52%) and 12 proband cases with ADCA III, but not in others. The CAG repeat was 21-33 in the disease-associated alleles (n=56), and 4-18 in normal alleles (n=1148). Expanded alleles were stable during transmission, and a significant inverse correlation for CAG repeat number with age at onset was noted. Our results indicate that SCA6 shares approximately half of the ADCA III in the Japanese, and that gene mutations causing the remaining, have yet to be identified.

Adult↗
PubMed1998

Extreme right lobar atrophy of the liver: a rare complication of autoimmune hepatitis.

Lobar atrophy is a rare morphologic change of the liver. We describe a 73-year-old woman with mild liver dysfunction and history of Sjögren's syndrome who had right hepatic lobar atrophy. Serum biochemistry levels were as follows: albumin, 4.5 g/dl; total bilirubin, 1.0 mg/dl; alanine aminotransferase, 25 international units/l; aspartate aminotransferase, 27 international units/l; alkaline phosphatase, 333 international units/l; and gamma-glutamyl transpeptidase, 332 international units/l. Serological data were as follows: rheumatoid factor, 27.9; anti-nuclear antibody, 1:640; and antismooth muscle antibody, 1:80. Viral markers for hepatitis B were all negative. Anti-hepatitis C virus (anti-c-100) was negative. Portal hypertension developed thereafter, and the patient died of hepatic failure at age 76. Postmortem examination revealed autoimmune hepatitis with moderate fibrosis, portal vein thrombus, and complete obstruction of the right hepatic duct due to hepatolithiasis. Terminal hepatic failure resulted from combination of decreased hepatic volume due to the right lobar atrophy, exacerbation of autoimmune hepatitis in the remnant left hepatic lobe, decreased portal venous blood flow due to thrombosis, portal hypertension, and cholangitis with hepatolithiasis. This is the first reported case of hepatic lobar atrophy due to autoimmune hepatitis. From a clinical standpoint, patients with hepatic lobar atrophy, even if asymptomatic, should be followed up with careful attention to progression of liver diseases, portal hypertension, and biliary complications.

Aged↗
PubMed1998

[Immunization with one dose of inactivated influenza vaccine].

In the winter of 1996, a total of 71 working adults from 20 to 60 (m = 37.3) years of age were immunized with one or two doses of inactivated influenza vaccine formulated in Japan. The reciprocal geometric mean hemagglutination inhibition antibody titers [mean HI] and the percentage with a hemagglutination inhibition titer of > or = x 128 [percent > or = x 128], against A/ Yamagata/32/89 (H1N1), A/Uhan/359/95 (H3N2), and B/Mie/1/93 were significantly elevated by either doses. The pre-/post-vaccination mean HI of H1N1 were 61.5/668.4 with one dose, and 85.7/637.3 with two doses. The percent > x 128 were 36.5/96.2 with one dose, and 47.4/94.7 with two doses. No significant differences were apparent between one and two doses. Similarly, nonsignificant differences were observed for the other two antigens contained in the vaccine. We observed the sufficient immune response to only one dose of inactivated influenza vaccine, which emphasizes the merit of one dose method of influenza immunization.

Administration, Oral↗
PubMed1998

Real-time evaluation of the effectiveness of microwave coagulation therapy for hepatocellular carcinoma using color Doppler imaging.

Percutaneous microwave coagulation therapy (PMCT) is a new technique for the treatment of hepatocellular carcinoma (HCC). However, it is difficult to distinguish those lesions in which necrosis has been induced from the viable residual lesions during the procedure, because the margin of the tumor becomes unclear during PMCT. We determined the area of necrotic lesions during the procedure using color Doppler imaging. PMCT was performed on 10 patients (17 lesions) with recurrent HCC. The electrode of the microwave delivery system was moved around the tumor and the surrounding area until color mosaic images disappeared from the entire area of the tumor. The areas in which necrotic tissue was indicated by color Doppler imaging were later confirmed by other modalities such as angiography or contrast-enhanced computed tomography. This leads us to believe that real-time, effective evaluation of PMCT is possible with color Doppler imaging.

Aged↗
PubMed1998

[Initial symptoms and mode of neurological progression in spinocerebellar ataxia type 6 (SCA6)].

Spinocerebellar ataxia type 6 (SCA6) is genetically defined as a group of SCA characterized by late-onset pure cerebellar ataxia clinically and by a small CAG repeat expansion in the gene encoding the alpha 1A-voltage-dependent-Ca channel subunit (CACNL1A4) on chromosome 19p13.1 genetically. We analyzed the initial symptoms and the mode of progression in this disorder on 25 genetically verified patients. The initial symptoms were recurrent episodes of transient vertigo (72%) or unsteady gait (28%). Neurologically, they showed apparent gaze-evoked nystagmus (92%), transient positional nystagmus (83%), and periodic alternating nystagmus (4%), in addition to cerebellar ataxia. In addition to these episodic symptoms, all patients developed progressive cerebellar ataxia over years. These fluctuating symptoms at the initial stage of the illness were clearly different from those of other SCA, rather overlapping with those of episodic ataxia type 2 (EA2), an allelic disorder of SCA6. The clinical similarity indicates that there might be a common mechanism at least in part causing these two disorders. The mode of progression and their neurological features were also presented.

Adult↗
PubMed1997

Erythropoietin and interleukin-3 activate tyrosine phosphorylation of CBL and association with CRK adaptor proteins.

Transformation of hematopoietic cells by the Bcr-abl oncoprotein leads to constitutive tyrosine phosphorylation of a number of cellular polypeptides that function in normal growth factor-dependent cell proliferation. Recent studies have shown that the CrkL adaptor protein and the Cbl protooncoprotein are constitutively tyrosine phosphorylated and form a preformed complex in cells expressing Bcr-abl. In the current study, we have examined cytokine-dependent tyrosine phosphorylation of Cbl and its association with Crk proteins. Erythropoietin (EPO) and interleukin-3 induced a dose and time-dependent tyrosine phosphorylation of Cbl in both EPO-dependent Ba/F3 and DA-3 transfectants, and the erythroid cell line HCD-57. Furthermore, once phosphorylated, Cbl associated with Crk adaptor proteins. Of the three Crk isoforms expressed in hematopoietic cells (CrkL, CrkII, and CrkI), tyrosine phosphorylated Cbl binds preferentially to CrkL and CrkII. The amount of Cbl associated with CrkL and CrkII exceeded the fraction of Cbl associated with Grb2 indicating that unlike other receptor systems, the Cbl-Crk association represents the dominant complex of Cbl in growth factor-stimulated hematopoietic cells. In factor-dependent hematopoietic cell lines, CrkL constitutively associated with the guanine nucleotide release factor, C3G, which is known to interact via Crk src-homology 3 (SH3) domains. Our data suggest that the inducible Cbl-Crk association is a proximal component of a signaling pathway downstream of multiple cytokine receptors.

Adaptor Proteins, Signal Transducing↗