Biomedical subjects

T Segawa

Publications and source records attributed to T Segawa.

At least 37 records · Page 2Linked to original sources

PubMed2000

Antibodies to different peptides in osteopontin reveal complexities in the various secreted forms.

We have generated synthetic peptides corresponding to various portions of human osteopontin (OPN) and have immunized rabbits and mice with these peptides to generate polyclonal and monoclonal antibodies specific to human OPN. We then generated six distinct sandwich enzyme-linked immunoabsorbent assay (ELISA) systems by using different pairs of polyclonal and monoclonal antibodies against human OPN. These systems allowed us to detect not only various isoforms and truncated forms of recombinant OPN, but also the glycosylated form of native urinary OPN. Most importantly, tumor-derived OPN was differentially detected by the six ELISA systems. The ELISA systems that we have developed will be useful for clarifying the functional roles for OPN in vivo in various physiologic and pathologic conditions.

Adult↗

PubMed2000

Multivariate analysis of prognostic determinants after surgery for renal cell carcinoma at Himeji National Hospital.

A clinico-pathological study was performed retrospectively on 62 patients who underwent surgery for renal cell carcinoma between January 1992 and October 1998 at Himeji National Hospital to clarify the prognostic determinants for survival. The median follow-up period was 32 months and the cause-specific survival rates at 1, 3 and 5 years were 86.7, 81.3, 81.3%, respectively. Of the 62 patients, 11 (17.7%) patients died of renal cell carcinoma and 2 (3.2%) patients died of unrelated causes. Of the variables related to survival, presenting symptoms, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), alkaline phosphatase (ALP), tumor size, pathological tumor grade, infiltration pattern, pathological tumor stage, N classification and M classification were significant risk factors for survival by univariate analysis. However, ALP, N classification and M classification were significant for survival as determined by the step-wise procedure and M classification was the most significant factor according to Cox's proportional hazard model analysis.

Adult↗

PubMed2000

Clinicopathological significance of fragile histidine triad transcription protein expression in endometrial carcinomas.

Abnormalities in structure and expression of the fragile histidine triad transcription (FHIT) gene have been reported in a variety of cancers, including endometrial cancers. A good correlation between FHIT gene alteration and loss of Fhit expression was observed in endometrial cancers, although those are the selected cases. Therefore, we investigated the association of Fhit expression with clinicopathological features in 111 cases of endometrial cancer. Loss of Fhit expression was associated with high malignant potential, including extensive muscular invasion, advanced surgical stage, high histological grade, nonendometrioid types of adenocarcinoma, negative estrogen receptor status, and p53 overexpression. The presence of personal cancer history was also related to the loss of Fhit with a marginal significance. Survival curves determined by the Kaplan-Meier method and univariate analysis demonstrated that decreased expression of Fhit was associated with a poor outcome. However, multivariate analysis using the stepwise Cox proportional hazard model showed that whereas lymph node metastasis, advanced stage, and high tumor grade were related to poor survival rates, loss of Fhit expression was not. Consequently, loss of Fhit expression is associated with advanced surgical stage and does not appear to be an independent prognostic factor in endometrial cancers, although a still larger sample of patients will be required to asses this issue definitively.

Acid Anhydride Hydrolases↗

PubMed2000

Water fat separation using the single acquisition "sandwich" type 3-point Dixon method to optimize knee joint scans.

In this paper, we tried to evaluate the effect of water-fat separation on and to optimize the scan condition of the newly developed "Sandwiched" 3-point Dixon method at 0.35 Tesla (T), for knee joint imaging. Using a 0.35T superconductive open magnet system with a solenoid type knee coil, one male and two female normal volunteers (27-37 y.o.) underwent knee joint imaging. Each sequence provided good water-fat separated images. At 0.35T, the gradient echo provided a better contrast than the spin echo. Optimal cartilage-marrow and cartilage-fluid contrast could be obtained at a frip angle (FA) of 90 degrees. There was no significant correlation between cartilage-marrow, cartilage-fluid contrast and repetition time (TR) values within the tested range. Cartilage-fluid and cartilage-marrow contrast were both best at an FA of 90 degrees with the gradient echo sequence. TR from 350 ms to 650 ms did not cause any significant contrast difference in the fat suppressed images. This method is useful and could be the only practical choice for obtaining fat suppressed T1 weighted images for joint magnetic resonance (MR) imaging at 0.35T.

Adipose Tissue↗

PubMed1999

Androgen receptor CAG repeat length polymorphism in benign prostatic hyperplasia (BPH): correlation with adenoma growth.

BACKGROUND: The androgen receptor (AR) gene has a polymorphic CAG microsatellite encoding variable-length glutamine repeats in the AR protein. The purpose of this study was to evaluate the association between the growth of benign prostatic hyperplasia (BPH) and the AR gene CAG repeat length. METHODS: We determined CAG repeat lengths in 176 BPH patients who underwent simple prostatectomy and in 41 control subjects without benign prostatic enlargement (non-BPE group). RESULTS: A statistically significant (P < 0.02) trend for large adenoma size with short CAG repeat length was found among the adenoma quartiles. CAG repeat length in the fourth quartile (large adenoma, 21.5 +/- 2.7) was significantly shorter than in the first quartile (small adenoma, 23.3 +/- 2.1, P < 0.02). It tended to be shorter than in the non-BPE group (23.1 +/- 2.4), but CAG repeat lengths in the entire BPH (22.4 +/- 2.5) and non-BPE groups did not significantly differ. The relative risk of large BPH (the fourth quartile) was 2.75 (95% confidence interval, 1.05-7.24; P < 0.05) on comparing CAG repeats of < or = 22-> or = 23. CONCLUSIONS: Shorter CAG alleles may be a genetic factor that promotes the growth of BPH.

Aged↗

PubMed1999

Fragile histidine triad transcription abnormalities and human papillomavirus E6-E7 mRNA expression in the development of cervical carcinoma.

BACKGROUND: Human papillomaviruses (HPV) are the most important etiologic factor for cervical carcinoma. However, additional cellular events may be necessary for malignant progression in the cervix. Recently, the fragile histidine triad (FHIT) gene, which is frequently lost in many cancers, was identified as a candidate tumor suppressor gene at chromosome 3p locus 14.2. METHODS: Thirty-five invasive cervical carcinomas (ICC), 13 Grade 2-3 cervical intraepithelial neoplasia specimens (high grade CIN), and 21 normal cervices were examined for expression of the FHIT gene and oncogenic HPV E6-E7 mRNA by reverse transcription-polymerase chain reaction (RT-PCR), and all of these FHIT cDNA were directly sequenced. RESULTS: Fourteen of 35 ICC (40%) showed abnormal FHIT transcription, whereas none of the high grade CIN or normal cervices had FHIT abnormalities. FHIT abnormalities included 13 short transcripts that were variously truncated between exons 4 and 8, 3 short transcripts with unknown sequences inserted, and 1 with no transcription. FHIT abnormalities were observed in all the small cell carcinomas, 4 of 7 adenocarcinomas and adenosquamous cell carcinomas (57%), and 7 of 25 squamous cell carcinomas (28%). Small cell carcinoma appeared to express the aberrant transcripts more frequently than squamous cell carcinoma (P=0.037). Immunohistochemical analysis showed that four ICCs with abnormal FHIT transcription did not express FHIT protein, whereas five of six CIN and ICC with no FHIT abnormality did express it. When expression of HPV E6-E7 mRNA was examined in the samples positive for HPV-DNA, E6-E7 transcripts were expressed in 7 of 9 high grade CIN (78%) and 18 of 28 ICC (64%). There was no difference in the frequency of HPV E6-E7 expression between CIN and ICC. In contrast, HPV E6-E7 expression was repressed in 8 of 10 (80%) ICC with FHIT abnormalities and in 2 of 18 (11%) in ICC with no FHIT abnormalities. CONCLUSIONS: Although E6-E7 genes of oncogenic HPV are important for the development of CIN and ICC, they may not be required for the development of carcinoma cells that have abnormal FHIT genes.

Acid Anhydride Hydrolases↗

PubMed1999

Effects of intraocular or systemic administration of neutralizing antibody against vascular endothelial growth factor on the murine experimental model of retinopathy.

Vascular endothelial growth factor (VEGF), the strongest known angiogenic cytokine and also a potent enhancer of vascular permeability, is closely associated with diabetic ocular complications and other intraocular neovascular diseases. The therapeutic effect of VEGF-neutralizing antibody on oxygen-induced retinopathy in an experimental murine model of proliferative retinopathy was investigated. Intraocular and systemic injection of the antibody resulted in 46% and 18% reductions in the number of nuclei of newly formed vessels of this model, respectively. The results demonstrated that a neutralizing antibody against VEGF was highly effective in the treatment of intraocular neovascularization and suggested possible modes of therapy in human intraocular neovascular diseases, including diabetic proliferative retinopathy.

Animals↗

PubMed1999

Insulin-induced hypoglycemia activates a chemokinergic neuronal pathway in the hypothalamo-pituitary system.

Recently, we found the presence of cytokine-induced neutrophil chemoattractant (CINC) neuronal pathway in the hypothalamo-pituitary system. This observation prompted us to investigate the effect of insulin-induced hypoglycemia on CINC neuronal pathway in the hypothalamo-pituitary system. An insulin injection decreased the plasma glucose level, which followed a prompt rise in plasma ACTH level and an increase in serum CINC level. Before the insulin injection, the signal for CINCmRNA was undetectable in the paraventricular hypothalamic nucleus (PVN). The hypoglycemic challenge induced strong hybridization signals of CINC mRNA in the parvocellular and magnocellular subdivision of the PVN within 30 min, and reached the peak within 3 h. No change was observed in the supraoptic nucleus after the hypoglycemic challenge. These studies demonstrate the presence of a hypoglycemia-sensitive chemokinergic neuronal pathway in the hypothalamo-neurohypophysial system and this newly described pathway will provide novel information for understanding pathophysiology of hypoglycemia.

Acute Disease↗

PubMed1999

Vascular endothelial growth factor and osteopontin in stage I lung adenocarcinoma.

Tumor growth and metastasis are angiogenesis-dependent processes initiated and regulated by a number of cytokines. Vascular endothelial growth factor (VEGF) is a potent angiogenic protein with a selective mitogenic effect on vascular endothelial cells. Osteopontin (OPN) induces endothelial cell migration and upregulates endothelial cell migration induced by VEGF. To clarify the cooperative role of VEGF and OPN in tumor angiogenesis, we stained VEGF, OPN, and CD34 immunohistochemically in 87 cases of stage I non-small cell lung cancer (adenocarcinoma, 55, and squamous cell carcinoma, 32). Of the 87 patients studied, 27 patients had postoperative relapse and 60 patients did not. VEGF was found in 34 of 55 cases of adenocarcinomas and 14 of 32 squamous cell carcinomas, and OPN was found in 30 of 55 adenocarcinomas and 10 of 32 squamous cell carcinomas. In adenocarcinoma, microvessel counts of VEGF-positive and OPN-positive tumors were significantly higher than VEGF-negative and OPN-negative tumors, respectively, whereas in squamous cell carcinoma they were not. More importantly, patients with VEGF- and OPN-positive stage I lung adenocarcinoma had significantly worse prognosis as compared with other groups. Cooperation of OPN is important in VEGF-mediated tumor angiogenesis in stage I lung adenocarcinoma.

Adenocarcinoma↗

PubMed1998

Effect of a topically applied neutralizing antibody against vascular endothelial growth factor on corneal allograft rejection of rat.

BACKGROUND: Studies in corneal transplant rejection remain important because acute immunologic rejection continues to be the leading cause of human corneal transplant failure. As the permeability of vessels and the neovascularization induce cells infiltration into the graft, we considered the possibility that vascular endothelial growth factor (VEGF), a potent permeability-increasing factor and angiogenesis-mediating factor, could participate in the immune response. METHODS: As the established corneal transplant model for rejection, the corneal transplant between Lewis and Fisher rats has been reported. First, we evaluated VEGF production in the graft by immunohistochemical method in the animal model. Next, we tried to neutralize the effect of VEGF by topical administration of anti-VEGF antibody. We administered anti-VEGF antibody as eye drops for 10 days just after the transplantation of the established animal corneal transplant model. RESULTS: VEGF was strongly produced from the infiltrative cells into the graft. Anti-VEGF antibody significantly suppressed the acute rejection compared with saline or rabbit IgG. CONCLUSIONS: The inhibition of VEGF by topically applied neutralizing antibody is a new potential therapeutic strategy for the treatment of corneal transplantation.

Administration, Topical↗

PubMed1998

Prostate-specific amplification of expanded polyglutamine expression: a novel approach for cancer gene therapy.

For cancer gene therapy, it is of primary importance to develop a system to sufficiently and selectively express therapeutic genes in cancer cells. In this study, we showed that an approximately 5.3-kb promoter region of the prostate-specific antigen (PSA) gene can replicate the endogenous expression pattern, although its expression is very weak. We then developed a novel two-step transcriptional activation system in which the PSA promoter drives an artificial transcriptional activator, GAL4-VP16 fusion protein, and it in turn activates transgene expressions under the control of GAL4-responsive elements. By using this system, transgene expressions can be greatly augmented while maintaining prostate-specific expression. Finally, we applied this system to drive an expanded polyglutamine, a potent proapoptotic molecule, to induce apoptosis selectively in PSA-positive prostate cancer cells. This novel system would provide an ideal approach for cancer gene therapy applicable not only to prostate cancer but to other cancers as well.

Apoptosis↗

PubMed1998

Structure-cytotoxic activity relationship for the toad poison bufadienolides.

The toad poison bufadienolides including natural and derivatized compounds were tested for their cytotoxic effects on primary liver carcinoma cells PLC/PRF/5 and their structure-cytotoxic activity relationships were studied. For this study, a ligand-binding model was developed by using a pharmacophore mapping program, Distance Comparisons (DISCO). The structural features that are common to the 3D structures of active bufadienolides were identified to provide approach to a 3D QSAR method by using Comparative Molecular Field Analysis (CoMFA) study and to correlate the steric and electrostatic fields of the molecules to their activities. A valuable model which enables prediction of their activities was obtained from the CoMFA analysis, which may be employed for the drug designs of new bufadienolide analogues.

Antineoplastic Agents↗

PubMed1998

Dopamine releases endothelium-derived relaxing factor via alpha 2-adrenoceptors in canine vessels: comparisons between femoral arteries and veins.

1. We investigated the role of vascular smooth muscle alpha-adrenoceptor subtypes in the vasoconstrictor response of femoral arteries and veins to dopamine and whether the vasoconstriction is modified by endothelium-dependent relaxation mediated via the activation of alpha 2-adrenoceptors in ring preparations of femoral arteries and veins from mongrel dogs. 2. Dopamine contracted both arteries and veins in a dose-dependent manner and this contraction was inhibited by pretreatment with phentolamine or prazosin. Pretreatment with yohimbine shifted the dose-response curve for dopamine to the right in femoral veins, but not in arteries. 3. Phenylephrine contracted femoral arteries and veins in a dose-dependent manner and this contraction was inhibited by pretreatment with prazosin. 4. Clonidine produced a bell-shaped dose-response curve in femoral veins and this curve was shifted upwards by pretreatment with NG-nitro-L-arginine (L-NNA). In contrast, femoral arteries were not affected by clonidine. NG-Nitro-L-arginine potentiated contractile responses to dopamine in both veins and arteries. This potentiation was inhibited by yohimbine or by the removal of the endothelium in both arteries and veins. 5. These results suggest that dopamine contracts femoral arteries via stimulation of alpha 1-adrenoceptors and contracts femoral veins via stimulation of both alpha 1- and alpha 2-adrenoceptors and that these contractions are attenuated by the vasodilator action of dopamine via alpha 2-adrenoceptor-mediated release of endothelium-derived relaxing factor.

Adrenergic alpha-Agonists↗

PubMed1998

[Combination therapy of daily intramuscular injection of interferon-alpha and oral administration of fluorouracil for advanced renal cell carcinoma].

BACKGROUND: To achieve optimum drug delivery of Interferon-alpha in treatment of renal cell carcinoma, a regimen consisting of its daily intramuscular administration, in combination with oral fluorouracil, was designed and carried out. Its efficacy is examined retrospectively. METHODS: In our department 7 patients with disseminated renal cell carcinoma were treated with daily intramuscular injection of interferon-alpha (3 x 10(6) IU) and daily oral administration of fluorouracil. All patient was nehprectomized before initiation of the regimen. RESULTS: Two patients achieved complete, and three patients achieved partial response radiographically (Overall response rate 71%). Metastatic sites of responders were lung (4) and pleura (2). The time required until response was 3.9 (median 5.4) months. In two responders, new lesions appeared in other organs despite durable response in initial pulmonary metastatic sites. There were two no-responders, one patient is alive with stable disease and the other patient died for progression of the disease. In all, two patients died of disease, one died for other cause, one surviving without evidence of disease, and three are surviving with disease. No significant side effect was noted in these seven patients. CONCLUSIONS: This regimen can be carried out on outpatient basis and considerable response can be expected for pulmonary and pleural lesions.

Administration, Oral↗

PubMed1998

[Intravesical bacillus Calmette-Guerin instillation for patients over 80 years old].

To study the efficacy and the safety of intravesical bacillus Calmette-Guerin (BCG) therapy for very elderly patients with superficial bladder cancer, we retrospectively compared patients over 80 years old who had received BCG therapy at our department between 1991 and 1996 (Group A; 10 patients 11 courses), with those below 80 years old (Group B, 17 patients 18 courses). In these patients, skin test reactivity to purified protein derivative showed a significant negative correlation with age (p = 0.016). No irreversible complications were observed in any patient. Persistence of acid-fast bacilli for more than one month after the termination of the course was observed in two patients in group A, and one in group B. A comparison of the cases undergoing eradicational BCG therapy in the two groups, grade 2 transitional cell carcinoma (TCC) was significantly more predominant than grade 3 TCC in group A (p = 0.004). (None of the tumors in group A were of grade 3) The disease-free rate was significantly lower in group A (p < 0.05), but 5 of the 10 patients in this group were finally disease-free. From these results, we conclude that intravesical BCG instillation therapy can be performed in patients over 80 years old, although a relatively lower disease-free rate is expected and special attention should be taken with regard to persistent BCG infection. The lower disease-free rate could be attributable to either diminished cellular immunity or a difference in tumor grade, although a definite conclusion could not be obtained here.

Administration, Intravesical↗

PubMed1998

[Vascular endothelial growth factor levels in the aqueous and serum in diabetic retinopathy with or without neovascular glaucoma].

We determined the levels of vascular endothelial growth factor/vascular permeability factor (VEGF/VPF) in the aqueous and serum in non-insulin dependent diabetic patients with proliferative retinopathy (n = 12) and neovascular glaucoma (n = 11). The aqueous levels of PEGF/VPF were significantly higher in both groups than in 10 diabetics without such complications. The levels were very high in patients with neovascular glaucoma, suggesting that VEGF/VPF is involved in the pathogenesis and progression of diabetic neovascular glaucoma. The serum levels were not significantly related to the presence or the stage of retinopathy. The findings suggest the possibility of treatment of neovascular glaucoma using anti- VRGF/VFP preparations.

Adult↗

PubMed1997

Successful endoscopic injection sclerotherapy for bleeding from bile duct varices.

A 66-year-old man who had undergone hepatic resection and choledochojejunostomy for intrahepatic stones was admitted with dark bloody stools. An endoscopic examination failed to detect the origin of bleeding in the esophagus, stomach, duodenum, or colon. Angiography showed an obstruction of the main trunk of the portal vein and marked cavernous formation of the collateral veins in the hepatoduodenal ligament. The patient was finally found to have variceal bleeding arising from the common bile duct; this was revealed by an endoscopic examination done through a jejunocutaneous fistula created later on. Thereafter, endoscopic injection sclerotherapy was successfully used to treat the hemobilia.

Aged↗

PubMed1997

Ocular vascular endothelial growth factor levels in diabetic rats are elevated before observable retinal proliferative changes.

Vascular endothelial growth factor (VEGF) is a potent angiogenic factor. VEGF levels in ocular tissue of 6-, 12-, 18- and 28-week-old Goto-Kakizaki (GK) rats, a well-known model of non-insulin-dependent diabetes, were evaluated by highly sensitive ELISA. VEGF concentrations in the GK rat as well as in non-diabetic Wistar rat significantly decreased from the age of 6 weeks to 18 weeks. However, although VEGF concentrations in the Wistar rat continued to fall significantly from 18 to 28 weeks of age, the levels were maintained between 18 and 28 weeks of age in GK rats. Levels were significantly different between the GK and Wistar rats at 28 weeks of age. Results of immunohistochemical studies of the eyes of Wistar and GK rats at 28 weeks of age suggest diffuse distribution of this cytokine in cells of neural origin. Weak to moderate VEGF immunoreactivity was exhibited mainly in the ganglion cell layer, inner plexiform layer and inner/outer nuclear layers in rats with and without diabetes. However, in the retinal optic nerve fiber layer, retinal pigment epithelium and choroid, strong VEGF immunoreactivity was noted only in the GK rat. In conclusion, increased VEGF production in certain ocular tissue, similar to that in humans, is observed quite early, at least before the appearance of observable retinal changes in the diabetic GK rat. This also suggests that the GK rat can be used as a model of initial or latent phase diabetic retinopathy.

Aging↗