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Biomedical subjects

T Kajiwara

Publications and source records attributed to T Kajiwara.

At least 55 records · Page 3Linked to original sources
PubMed2000

Mixed-Valent Heptairon Complex with a Ground-State Spin Value of S=12/2 Constructed from a Triiron Cluster Ligand.

The anionic triiron(III) cluster ligand [Fe(III)(3)(µ(3)-O)(bpca)(2)Cl(4)(EtO)(2)](-) (1; Hbpca=bis(2-pyridylcarbonyl)amine) was prepared as a building block for constructing larger metal assemblies. This "metal cluster complex ligand" was used in the synthesis of the mixed-valent heptairon complex [Fe(II)(1)(2)(EtOH)(2)], which has a ground-state spin value of S=12/2.

Journal Article↗
PubMed2000

Allelic loss at 1p34-36 predicts poor prognosis in node-negative breast cancer.

Allelic losses of specific chromosomal regions in the DNA of tumor cells, which imply loss of tumor suppressor genes normally resident at those loci, may become useful postoperative prognostic indicators for breast cancers that have not yet metastasized to lymph nodes. To examine whether specific allelic losses might correlate with postoperative disease-free survival, we tested tumors from a cohort of 228 node-negative breast cancer patients for allelic losses at 18 microsatellite loci chosen to represent either a known tumor suppressor gene or a region where genetic alterations are frequent in breast tumors. We followed the patients clinically for 5 years or until death (if patient death occurred before completion of 5 years of follow-up). Patients whose tumors had lost an allele at 1p34-36 bore significantly higher risks of postoperative recurrence than those whose tumors retained both alleles of the markers in that region [the 5-year recurrence rate was 15% among patients with losses versus 2% among patients with retention (P = 0.001)]. Multivariate analysis demonstrated that allelic loss at 1p34-36 was an independent postoperative predictor of shorter disease-free survival (hazard ratio, 5.8; P = 0.0117). Thus, allelic losses at 1p34-36 in a tumor might have a potential to serve as a negative prognostic indicator to guide postoperative management of breast cancer patients, especially in the selection of high-risk women who will benefit from adjuvant chemotherapy and endocrine therapy.

Adult↗
PubMed2000

Molecular characterization of fatty acid alpha-hydroperoxide-forming enzyme (alpha-oxygenase) in rice plants.

Genes encoding an alpha-oxygenase, in Nicotiana tabacum and Arabidopsis thaliana, have been recently isolated. However, the reaction mechanism of the enzyme has not so far been elucidated. In this study, a cDNA encoding the fatty acid alpha-oxygenase gene in rice plants was isolated. The deduced amino acid sequence showed high similarity (63.6%) to that of N. tabacum. The gene was cloned into an expression vector system, pQE-30, and expressed in Escherichia coli as a host cell. Palmitic acid as a substrate was incubated with the lysate of the cells, and the products were analysed by HPLC. A compound formed predominantly by the recombinant enzyme was shown to be n-pentadecanal. By incubating the mixture at 0 degrees C, 2-hydroperoxypalmitic acid was detected as a primary product and little formation of n-pentadecanal was detected. Furthermore, uptake of molecular oxygen was observed with an oxygen electrode. This indicated that the gene in rice plants encodes the alpha-oxygenase.

Arabidopsis↗
PubMed2000

A lipid-hydrolysing activity involved in hexenal formation.

Short-chain aldehydes such as (3Z)-hexenal and n-hexanal are formed from lipids through sequential actions of lipid-hydrolysing, lipoxygenase and fatty acid hydroperoxide lyase activities. The aldehydes are formed upon wounding of plant tissues, and are reported to have bactericidal and fungicidal activities. Furthermore, it has been reported that the aldehydes can induce expression of a subset of genes involved in disease resistance and that they are involved in a defence response against insect herbivores. Although several genes encoding lipoxygenases and the lyases have been isolated, and characterized to some extent, only little is known about the enzyme accountable for the lipid-hydrolysing step. In this study, we tried to characterize the lipid-hydrolysing activity involved in the short-chain aldehyde formation in Arabidopsis. When Arabidopsis leaves were homogenized, (3Z)-hexenal was formed rapidly within a few minutes. During this time period, the amount of alpha-linolenic acid and C(16:3) rapidly decreased. Such a rapid increase of the aldehyde was repressed almost completely when the leaves were homogenized under a nitrogen stream, and instead free trienoic acids accumulated. A lipase inhibitor, quinacrine, successfully repressed the hydrolysis. It was revealed that trienoic acids in monogalactosyldiacylglycerol were predominantly hydrolysed during the formation of short-chain aldehydes. Collectively, it is suggested that the lipolytic enzyme involved in the short-chain aldehyde formation is a galactolipid-specific lipase.

Arabidopsis↗
PubMed1999

Correlation of Allelic Loss with Poor Postoperative Survival in Breast Cancer.

BACKGROUND: Allelic losses of tumor suppressor genes or the chromosomal regions harboring them in the DNA of tumor cells may become useful postoperative prognostic indicators. METHODS: To examine whether specific allelic losses correlate with postoperative survival in a five-year prospective follow-up, we tested tumors from a cohort of 504 breast cancer patients for allelic loss of 18 microsatellite markers representing either known tumor suppressor genes or regions where genetic alterations are frequent in breast tumors. RESULTS: Patients with allelic loss at 1p34, 3p25, 8p22, 13q12, 17p13.3, or 17q21.1 had a significantly higher risks of postoperative mortality compared withthose whose tumors retained both alleles at those loci (at 1p34, the 5-year mortality rate was 23% among patients with loss vs 10% with retention, p 0.0100; at 3p25, 22% vs 9%, p =0.0014; at 8p22, 24% vs 7%, p =0.0177; at 13q12, 19%vs 8%, p=0.0093; at 17p13.3, 19% vs 9%, p=0.0078; and at 17q21.1, 17% vs 10%, p =0.0475). CONCLUSION: Allelic losses at these loci can serve as negative prognostic indicators to guide post-operative management, especially in the selection of thosewho will benefit from intensive adjuvant therapies.

Journal Article↗
PubMed1999

Maximum Density of Tumor Staining Obtained by Preoperative IV-DSA as a Prognostic Indicator for Node-Negative Breast Cancer.

BACKGROUND: We previously demonstrated that the density of tumor enhancement by intravenous digital subtraction angiography (IV-DSA) is correlated with the number of tumor microvessels and that the incidence of distant metastasis is highin patients with breast cancer who show a high maximum density of tumor enhancement (MAX) on IV-DSA. In the present study, we evaluated the prognostic value ofMAX for node-negative breast cancer patients. Patients and METHODS: A total of 128 node-negative breast cancer patients underwent preoperative IV-DSA, and the region of interest (ROI) was set in the areas enhanced by IV-DSA of the breast. MAX was calculated by the time-density curve. Patients were divided into two subgroups: those with MAX >/= 9 (n=35) and those with MAX < 9 (n=93). RESULTS: Patients with recurrence had a significantly higher MAX value than those without recurrence (11.8 +/- 3.8 vs 7.1 +/- 3.0, p<0.01). The disease-free survival rate was significantly worse in patients with higher MAX values than in those with lower MAX values (p <0.001). Multivariate analysis showed that MAX was the strongest predictor of disease-free survival (p =0.026). CONCLUSIONS: These results suggest that the maximum density obtained by IV-DSA is a strong, independent prognostic indicator for node-negative breast cancer patients.

Journal Article↗
PubMed1999

Accelerated rejection of Fas ligand-expressing heart grafts.

The Fas/Fas ligand (FasL) system plays an important role in the induction of lymphoid apoptosis and has been implicated in the suppression of immune responses. Recently, there has been renewed interest in immune privilege, as it was shown that two privileged sites (the eye and testes) constitutively express FasL, which kills lymphoid cells that invade these areas. We have established murine FasL-transgenic mice (B6) under the control of the cardiac alpha-myosin heavy chain promotor, and transplanted FasL-expressing F1(B6 x C3H/HeJ) heart grafts into syngeneic (F1) and allogeneic (C3H/HeJ) recipients. FasL-expressing F1 heart allografts placed in C3H/HeJ recipients as well as FasL-expressing F1 isografts placed in nontransgenic and FasL-transgenic F1 were more rapidly rejected, and their survival was much shorter than that of nontransgenic control F1 allografts placed in C3H/HeJ. Native control and FasL-expressing hearts looked normal in mice up to 8 wk of age on hematoxylin-eosin staining. Control heart allografts undergoing ordinally acute rejection showed moderate focal lymphocyte infiltrates, while FasL-expressing F1 allografts and isografts showed massive hemorrhage, edema, and massive neutrophil infiltration as early as 1 day after transplantation. In conclusion, FasL expression and surgical procedure (ischemia/reperfusion) were synergistic in the induction of accelerated heart graft rejection, while allogenicity was not necessary. It may be necessary to find ways of controlling neutrophilic reaction/apoptosis in infiltrating lymphocytes to use FasL in clinical organ transplantation.

Animals↗
PubMed1999

CD95 ligand expression enhances growth of murine renal cell carcinoma in vivo.

The CD95/CD95 ligand (CD95L) system plays an important role in the induction of lymphoid apoptosis and has been implicated in the suppression of immune responses. In this system, two murine CD95L-transfected renca clones and a control renca clone transfected only with the vector were implanted into the subcapsule of the left kidney of Balb/c and Balb/c nude mice. Both CD95L-expressing and control renca clones formed macroscopic tumors in all of the Balb/c and Balb/c nude hosts 14 days after implantation. Growth of tumors of murine CD95L-transfected renca cells was significantly better than that of control renca cells in Balb/c mice, while the growth advantage of CD95L transfectants was not observed in Balb/c nude mice. Lymphocytes underwent apoptosis mainly in the periphery of the CD95L-expressing tumors but not in control tumors grown in Balb/c mice, while lymphocytes undergoing apoptosis were not observed in CD95L-expressing tumors or in control tumors grown in Balb/c nude mice. Neutrophilic recruitment was rarely observed in CD95L-expressing or control tumors. CD95L expressed on renca cells possibly suppressed immune responses against renca tumors by inducing apoptosis of the infiltrating lymphocytes. However, CD95L-expressing renca cells did not form tumors in the renal subcapsule of allogeneic C3H/HeJ mice.

Animals↗
PubMed1999

Phase II study of KRN8602, 3'-deamino-3'-morpholino-13-deoxo-10-hydroxycarminomycin hydrochloride, MX2 x HCl in patients with metastatic breast cancer.

PURPOSE: KRN8602 (3'-deamino-3'-morpholino-13-deoxo-10-hydroxycarminomycin hydrochloride, MX2 x HCl) is a newly developed anthracycline that has been found to be effective against multidrug-resistant tumor cells in vitro and in vivo. In order to clinically confirm these promising preclinical observations, we performed a phase II trial of KRN8602 in patients with anthracycline-resistant metastatic breast cancer. METHODS: Of 41 patients registered with metastatic breast cancer, 37 were eligible and were given at least two cycles of KRN8602 15 mg/m2 per day at 3-4 week intervals by intravenous bolus injection on days 1, 2, and 3. RESULTS: Of the 37 patients, 6 (16.2%, with a 95% confidence interval of 4.3-28.1%) had a partial response (PR). No complete responses (CRs) were observed. The difference between response rates according to prior history of anthracycline administration was not significant. Myelosuppression was moderately severe, with grade 3 or 4 leukopenia occurring in 65%. Severe nausea/vomiting was observed in 44% of the patients. CONCLUSIONS: The results indicate that KRN8602 has modest activity in refractory metastatic breast cancer and is associated with relatively severe toxicity. Furthermore, the preclinical finding that KRN8602 overcomes anthracycline resistance was not reliably reproduced in this clinical phase II trial.

Adult↗
PubMed1999

QT dispersion in patients with Duchenne-type progressive muscular dystrophy.

BACKGROUND: A high degree of QT dispersion is a risk factor for arrhythmic sudden death in patients with myocardial infarction and cardiomyopathy. Duchenne-type progressive muscular dystrophy (DMD) is also associated with the development of ventricular arrhythmias. The purpose of this study was to determine the relationship between QT interval dispersion and ventricular arrhythmias in patients with DMD. METHODS: Sixty-seven patients with DMD were studied. Standard 12-lead electrocardiograms and 24-hour Holter electrocardiograms were recorded, and the QT interval was determined in every lead of the standard electrocardiogram to determine the QT dispersion. QT dispersion was compared with the frequency of ventricular arrhythmias and the severity of skeletal muscle damage on the basis of the Swinyard and Deaver 8-stage scale. RESULTS: QT dispersion in all 67 patients averaged 54 +/- 18 ms. The QT dispersion was 49 +/- 16 ms in stage 5 patients, 61 +/- 22 ms in stage 6 patients, 52 +/- 17 ms in stage 7 patients, and 56 +/- 17 ms in stage 8 patients. Ventricular arrhythmias of Lown grade III or higher were observed in 3 of 35 patients with QT dispersion <60 ms and in 14 of 32 patients with QT dispersion >/=60 ms. Logistic regression analysis demonstrated that QT dispersion is an independent risk factor for ventricular arrhythmias of grade III or higher in patients with DMD. CONCLUSIONS: The incidence of ventricular arrhythmias of Lown grade III or higher was greater in patients with QT dispersion >/=60 ms than in patients with QT dispersion >60 ms. QT dispersion therefore is a risk factor for serious ventricular arrhythmias in patients with DMD.

Adolescent↗
PubMed1999

The expression of variant exon v7-v8 CD44 antigen in relation to lymphatic metastasis of human breast cancer.

The purpose of this prospective study was to evaluate the expression of CD44 splice variant epitopes in human breast cancer and their potential as prognostic indicators. Invasive breast cancer tissues obtained from 91 patients were examined for expression of the standard CD44 antigen and variant CD44 antigens (v5, v6, v7, v7-v8, and v8-v10) by immunohistochemical staining to investigate the relations of these antigens to clinicopathological factors and prognosis. The expression of standard CD44 antigen was detected in 54.9% of 91 patients with primary human breast cancer. The variant epitopes of CD44 examined, i.e., v5, v6, v7, v7-v8, and v8-v10, were expressed in 54.9%, 54.9%, 0%, 34.1%, and 0%, respectively. There was a significant difference in tumor size, lymph nodal status, and degree of lymphatic permeation between patients who were positive for exon v7-v8 and those negative for this variant (p < 0.01). Prognosis was also significantly worse in patients positive for CD44 v7-v8 than in those negative for this variant. However, multivariate analysis with the three prognostic indicators tumor size, lymph nodal status, and the degree of lymphatic invasion, has shown that the expression of CD44 v7-v8 antigen in breast carcinoma was not a significant independent prognostic factor and was closely dependent on lymphatic invasion and nodal status. Fourteen of 31 patients who were positive for CD44 v7-v8 experienced recurrences. The mode of recurrence was lymphatic metastasis in 10 out of these 14 patients. Breast cancer cells expressing v7-v8 CD44 antigen have an extremely high affinity for lymph nodes and lymphatic vessels, and are likely to metastasize to distant lymph nodes even at a very early stage in the progression of this disease. This suggests that not only the anatomical factors but also organ affinity plays an important role in the establishment of lymph nodal metastasis of breast cancer.

Adult↗
PubMed1999

Prognostic significance of MIB1-determined proliferative activities in intraductal components and invasive foci associated with invasive ductal breast carcinoma.

The prognostic significance of the proliferative activities in intraductal components and invasive foci was investigated using 157 cases of invasive ductal breast carcinoma in which intraductal components predominated. Proliferative activity was expressed as the number of MIB1-positive nuclei per 1000 cancer cells in the most active areas of intraductal components (MLI-DCIS) or invasive foci (MLI-INV). MLI-DCIS correlated closely with MLI-INV (r = 0.710, 95% confidence interval, 0.623-0.780; P < 0.0001). Both MLI-DCIS and MLI-INV were related to oestrogen receptor (ER) (P = 0.0006, P = 0.0028 respectively), grade of invasive tumour (P < 0.0001, P < 0.0001 respectively) and classification of intraductal components (P < 0.0001, P < 0.0001 respectively). In the univariate disease-free survival analysis, both MLI-DCIS and MLI-INV were found to be significant (P < 0.0001, P = 0.0003 respectively). However, in node-negative cases, only MLI-DCIS was significant (P = 0.0416). Multivariate analysis revealed that MLI-DCIS was significant not only in all cases, but also in node-negative cases (P = 0.0223, P = 0.0426 respectively), whereas MLI-INV was not. These findings indicate that MIB1-determined proliferative activity of intraductal components is a significant prognostic determinant of invasive ductal breast carcinoma in which intraductal components predominate.

Adult↗
PubMed1999

Clinical evaluation of endoscopic injection sclerotherapy using n-butyl-2-cyanoacrylate for gastric variceal bleeding.

BACKGROUND: Emergency endoscopic injection sclerotherapy (EIS) has been applied to the initial treatment of gastric variceal bleeding and various methods have been attempted. METHODS: Emergency EIS was performed on 38 patients with gastric variceal bleeding using either the ethanolamine oleate (EO) method or n-butyl-2-cyanoacrylate (Histoacryl) method and the outcome was compared. RESULTS: Complete haemostasis was defined as continuous haemostasis lasting for 14 days or more. Complete haemostasis was achieved in 52.4% of patients in the EO method versus 100% of those treated with the Histoacryl method, a significant difference, suggesting that the Histoacryl method was superior for achieving haemostasis in an emergency. The cumulative non-bleeding rate was also significantly higher in patients treated with Histoacryl, indicating the durability of haemostasis. There were no serious complications in patients who received either method of sclerotherapy. Post-EIS surgery was required in 42.8% of patients treated with EO, while no surgery was required in those treated with Histoacryl, supporting the greater haemostatic effect of Histoacryl. Although there was no significant difference in the cumulative survival rates of patients treated by these two methods, death from haemorrhage was avoided by using Histoacryl. CONCLUSIONS: Based on these results, the Histoacryl method is thought to be the initial treatment of choice for gastric variceal bleeding, because it achieved superior haemostasis compared with EO and death by haemorrhage was avoided.

Emergencies↗
PubMed1999

Effect of Bcl-2 overexpression in human prostate cancer cells in vitro and in vivo.

BACKGROUND: Cancer cells often develop mechanisms to resist apoptosis and the extent of such anti-apoptotic ability has been shown to parallel tumor progression in various malignancies. Among various molecules implicated in regulating apoptosis pathway, bcl-2 and its family members are best characterized. METHODS: To investigate the effect of bcl-2-mediated anti-apoptotic ability on tumor growth and progression in prostate cancer, a cell line overexpressing bcl-2 (LNCaP/bcl-2) was established by genetically engineering a prostate cancer cell line LNCaP. Tumor growth of LNCaP/bcl-2 was compared with the parental cell line in vitro and in vivo. RESULTS: LNCaP/bcl-2 cells show resistance to apoptosis caused by nutrient deprivation and did not arrest when cultured in serum-free or androgen-free medium, while parental LNCaP cells or LNCaP cells transfected with the vector only (LNCaP/control) underwent extensive apoptosis on nutrient deprivation and sustained growth suppression in serum-free or androgen-free medium. When injected subcutaneously into nude mice, tumors deriving from LNCaP/bcl-2 cells grew faster compared with LNCaP/control for about 3 weeks (P = 0.02), but this effect was not evident after 5 weeks. Upon castration, the control tumors regressed but LNCaP/bcl-2-derived tumors showed resistance, as was previously reported. CONCLUSIONS: These data confirm the notion that anti-apoptotic function of bcl-2 is oncogenic and confers resistance to androgen deprivation and also indicate that it may also play a critical role in earlier stages of tumorigenesis.

Androgens↗
PubMed1999

Molecular cloning and expression of Arabidopsis fatty acid hydroperoxide lyase.

Fatty acid hydroperoxide lyase (HPOL), an enzyme of the octadecanoid pathway that forms carbon-6 aldehydes such as n-hexanal or (Z)-3-hexenal, was cloned from Arabidopsis thaliana as a full-length cDNA. The HPOL activity obtained by expressing the cDNA in Escherichia coli formed n-hexanal from linoleic acid 13-hydroperoxide, whereas linoleic acid 9-hydroperoxide was not a substrate for the enzyme. The HPOL mRNA is expressed at low level in leaves; however, its accumulation can be found in the inflorescence. Wounding or methyl jasmonate treatments increase the mRNA level in leaves. These results indicate that the HPOL gene is up-regulated in leaves in response to wounding and that the enzyme may be an active component of the octadecanoid defense response.

Aldehyde-Lyases↗