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Biomedical subjects

T Saeki

Publications and source records attributed to T Saeki.

At least 91 records · Page 5Linked to original sources
PubMed1997

[A case of complete remission of gastric endocrine cell carcinoma with multiple bone metastasis by combination chemotherapy and high-dose chemotherapy with autologous peripheral blood stem cell transplantation].

A 31-year-old man was admitted to our hospital complaining of epigastric discomfort and severe lumbago. An upper gastrointestinal endoscopy revealed several submucosallike tumors. Histologic examination of biopsy specimens confirmed the presence of endocrine cell carcinoma. Gallium scintigraphy and CT revealed multiple bone metastasis. He was treated with 6 cycles of combination chemotherapy consisting of CDDP, etoposide, CPA, EPI and VCR. Both gastric tumors and bone metastasis completely disappeared. After 7 cycles of the chemotherapy, he was treated with HDCT with PBSCT. There was no severe complication. This result suggested that the combination of conventional chemotherapy and HDCT with PBSCT was useful in cancer patients with poor prognoses, such as advanced gastric endocrine cell carcinoma.

Adult↗
PubMed1996

Anti-atherosclerotic effect of E5324, an inhibitor of acyl-CoA:cholesterol acyltransferase, in Watanabe heritable hyperlipidemic rabbits.

E5324, n-butyl-N'-[2-[3-(5-ethyl-4-phenyl-1H-imidazol-1-yl)propoxy]-6- methylphenyl]urea, a novel and potent inhibitor of acyl-CoA:cholesterol acyltransferase (ACAT), was evaluated for its anti-atherosclerotic and lipid-lowering effects in Watanabe heritable hyperlipidemic (WHHL) rabbits. At 3 months of age, 40 male WHHL rabbits were divided into 4 groups. The rabbits were fed a standard rabbit chow (control group), or standard rabbit chow containing E5324 (0.1% or 0.02%) or 1% probucol for 16 weeks. Even the high dose of E5324 did not lower the plasma total cholesterol levels throughout the experiment. Probucol slightly reduced the plasma cholesterol levels, and showed anti-atherosclerotic activity, i.e., reductions of atherosclerotic plaque formation and cholesterol content in the aorta. Although E5324 did not lower plasma cholesterol, atherosclerotic plaque formation in the aortic arch and thoracic aorta was reduced (by about 34% and 41%, respectively, at the high dose; P < 0.05). Cholesterol content in the aortic arch and thoracic aorta was also reduced (by about 59% and 62% at the high dose, respectively) compared with the control. These results suggest that E5324 acts directly on the arterial wall through ACAT inhibition, and prevents the progression of atherosclerosis in WHHL rabbits.

Analysis of Variance↗
PubMed1996

High prevalence of serum apolipoprotein E4 isoprotein in rheumatoid arthritis patients with amyloidosis.

OBJECTIVE: To determine whether serum Apolipoprotein E (Apo E) type 4 isoprotein is a risk factor for the development of amyloidosis in patients with rheumatoid arthritis (RA). METHODS: Using isoelectric focusing, we studied Apo E phenotype expression and the corresponding allele frequencies (epsilon 2, epsilon 3, and epsilon 4) in 35 patients with RA and amyloidosis, 65 patients with RA and without amyloidosis, and 63 healthy controls. RESULTS: The Apo E3/4 phenotype was significantly more common in the group with amyloidosis (31.4%) than in the patients without amyloidosis (12.3%; P < 0.05) or in healthy controls (12.7%; P < 0.05). The frequency of the epsilon 4 allele was significantly greater in the group with amyloidosis (0.16) than in the patients without amyloidosis (0.07; P < 0.05) or in healthy controls (0.07; P < 0.05). CONCLUSION: The presence of Apo E4 isoprotein may be a risk factor for the development of amyloidosis in patients with RA.

Adult↗
PubMed1996

Proliferation of osteoclast-like giant cells in a metastatic bone tumor from stomach cancer: report of a case and analysis of the autopsy findings.

A 70-year-old man who had undergone esophagectomy with reconstructive surgery using a portion of the stomach 5 years earlier for esophageal cancer was admitted to our hospital after a routine endoscopy and histological examination of a biopsy specimen revealed poorly differentiated adenocarcinoma in the stomach. A gastrectomy and intrathoracic esophagojejunostomy was performed on January 20, 1993; however, the patient suffered a cerebral infarction and died of septic shock on April 9, 1993. At autopsy, metastatic tumors were macroscopically observed in various organs, including a bone tumor measuring 1.0 cm in diameter in the L4 vertebra. To clarify the origin of the bone tumor, we conducted histological and immunohistochemical examinations. Histological examination revealed a mixture of osteoclast-like giant cells (OGCs) and poorly differentiated adenocarcinoma cells, although no histologic features of OGCs were observed either in a primary site or in any of the multiple metastatic lesions. On immunohistochemistry, adenocarcinoma cells in the bone stained positively for the carcinoembryonic antigen (CEA), whereas no staining for CEA was observed in the OGCs which demonstrated negative staining for all the antigens of epithelial markers. These findings led us to conclude that this bone tumor had metastasized from the stomach cancer and that the OGCs may have originated from mesenchymal cells reacting to the adenocarcinoma cells.

Adenocarcinoma↗
PubMed1996

Mechanisms of satigrel (E5510), a new anti-platelet drug, in inhibiting human platelet aggregation. Selectivity and potency against prostaglandin H synthases isozyme activities and phosphodiesterase isoform activities.

Satigrel (E5510, 4-cyano-5,5-bis(4-methoxyphenyl)-4-pentenoic acid) is a potent inhibitor of platelet aggregation. Like cyclooxygenase/prostaglandin H synthase (PGHS) inhibitors such as aspirin, which suppress platelet aggregation by inhibiting thromboxane A2 production, satigrel inhibits collagen- and arachidonic acid-induced aggregation of human platelets. In contrast to other PGHS inhibitors, satigrel, like cyclic nucleotide phosphodiesterase (PDE) inhibitors such as cilostazol, shows inhibitory activity against thrombin-induced platelet aggregation. To investigate the mechanism of the anti-platelet activity of satigrel, we examined the selectivity and potency of satigrel against PGHS isozyme activities and PDE isoform activities. Two isozymes of PGHS are known; constitutive enzyme (PGHS1) and inducible enzyme (PGHS2). Satigrel showed inhibitory activity against PGHS1 (IC50: 0.081 microM) and PGHS2 (IC50: 5.9 microM), suggesting the selective inhibition of PGHS1. Indomethacin, which is a selective inhibitor of PGHS1, showed similar selectivity against PGHS isozymes (IC50: 0.12 microM and 1.4 microM, respectively). These results support that satigrel suppresses thromboxane A2 production by inhibiting PGHS1. It is known that three isozymes of PDE exist in human platelets: Type V, which specifically hydrolyzes guanosine 3',5'-cyclic monophosphate (cGMP), Type III, which mainly hydrolyzes cAMP, and Type II, which hydrolyzes both cGMP and cAMP. We separated these three isozymes from human platelets and examined the inhibitory activity of satigrel against each enzyme. Of the three isozymes, the inhibitory activity of satigrel was the most potent against Type III PDE (IC50: 15.7 microM). The IC50 value for Type III corresponded with that for thrombin-induced platelet aggregation. Type V and Type II were also inhibited by satigrel (IC50: 39.8 and 62.4 microM, respectively). In human platelets, satigrel increased both cAMP and cGMP levels in a dose-dependent manner (100, 300 microM). In conclusion, satigrel inhibits collagen- and arachidonic acid-induced platelet aggregation through preventing thromboxane A2 synthesis by selective inhibition of the target enzyme, PGHS1, which exists in platelets. The anti-aggregating activity of satigrel against thrombin-induced aggregation may be due to elevation of the cyclic nucleotide levels through the inhibition of PDE isozymes.

Blood Platelets↗
PubMed1996

Adrenocorticotropin-independent bilateral macronodular adrenocortical hyperplasia: immunohistochemical studies of steroidogenic enzymes and post-operative course in two men.

We treated two men with Cushing's syndrome due to adrenocorticotropin (ACTH)-independent bilateral macronodular adrenocortical hyperplasia (AIMAH). In both patients, plasma ACTH was low and plasma cortisol was not suppressed by a high dose of dexamethasone (8 mg) but was remarkably responsive to exogenous ACTH. The adrenal glands were extremely enlarged and contained multiple nodules composed of large clear cells and small compact cells. The immunoreactivity of P-450(17) alpha was predominant in the small compact cells, while that of 3 beta-hydroxysteroid dehydrogenase (3 beta-HSD) was observed exclusively in the large clear cells. Among various adrenocortical disorders, differential expression of 3 beta-HSD and P-450(17) alpha in clear and compact cells has heretofore been demonstrated only in AIMAH. Total adrenalectomy was done for one patient, and partial adrenalectomy for the other. In the former patient, the normal diurnal rhythm of plasma ACTH was restored 11 months postoperatively. In the latter patient, the normal dynamics in the hypothalamic-pituitary-adrenal axis became evident 15 months after surgery. Thus AIMAH is apparently a primary adrenocortical disorder and is not due to abnormalities of the hypothalamus or pituitary.

3-Hydroxysteroid Dehydrogenases↗
PubMed1996

Analysis of local recurrences after breast conserving therapy using postoperative radiotherapy.

One hundred and ninety-one breast cancer patients had breast conserving therapy (lumpectomy and postoperative radiotherapy) at the Shikoku Cancer Center Hospital between July 1989 and December 1994. Seven patients developed recurrence, two of them experienced recurrence in the treated breast after a median follow-up of 27 months. One of the two patients with the local recurrence had an inflammatory cancer-like change in the treated breast which consisted of a diffuse induration in the breast and thick overlying skin with redness. It was very difficult to distinguish local recurrence from the local change due to radiation. Her primary tumor showed prominent lymphatic vessel involvement, although the surgical margins were negative histologically. We believe that the possible lymphatic retention after axillary dissection facilitated this type of progression of the residual tumor cells within the lymphatic vessels. Although this type of local recurrence is quite rare, it could cause distant metastases. Reanalysis of surgical treatment and postoperative adjuvant therapy for the patients with breast cancer showing prominent lymphatic vessel involvement is required.

Adult↗
PubMed1996

[Intrahepatic arterial infusion chemotherapy for the colon cancer patients with liver metastases--a comparison of arterial embolization chemotherapy versus continuous arterial infusion chemotherapy].

To compare the prognostic benefit between arterial embolization chemotherapy (AEC) and continuous arterial infusion chemotherapy (CAIC), we clinicopathologically examined 32 colorectal cancer patients with liver metastases. Seventy patients were treated with AEC, and 15 patients with CAIC. In the AEC regimen, either ADR or CDDP dissolved in Lipiodol was infused by the implanted reservoir every one to two months. Otherwise, for the CAIC regimen, 360 mg/m2/day of 5-FU was continuously infused by the reservoir for 14 days. Subsequently, on day 22 after the initial 5-FU infusion, 180 mg/m2/day of 5-FU was continuously infused for 7 days. After a 7-day interval without infusion, 180 mg/m2/day of 5-FU was infused for 7 days. This 7-day infusion/7-day no-infusion cycle was repeated. The efficacy of the AEC was 6% (1 PR + 7 NC + 9 PD), CAIC (6 PR + 4 NC + 5 PD), suggesting that CAIC provides the better response rate. With regard to prognosis, the 1- and 2-year survival rates of AEC were 63% and 19%, respectively. The median survival time was 415 days. Otherwise, the 1- and 2-year survival with CAIC was 54% and 40%, respectively, and the median survival time was 470 days. No significant difference between the AEC and the CAIC was observed in the colorectal cancer patients with liver metastases.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1996

[The genomic organization of the mouse adrenocorticotropin receptor].

As a step for analysis of the transcriptional regulation of the adrenocorticotropin (ACTH) receptor gene, I have made an attempt to obtain a full length cDNA and determined the genomic organization of the mouse ACTH receptor. Using the 5'-RACE (rapid amplification of cDNA ends) method, a 374bp sequence upstream of the translation start codon ATG of the receptor was obtained. By comparison of the 374bp sequence with the 1.8kb genomic sequence within the phage clone, lambda mCTR8, containing the mouse ACTH receptor coding region as described previously, a 95bp sequence of the 5'-RACE-generated cDNA was found to locate from the position of -1 to -95 from the ATG, and a 113bp sequence of the 5'-RACE-generated cDNA was found in the genomic sequence approximately 1.6kb upstream of the ATG. Because of the absence of a 166bp sequence, -209 to -374, in lambda mCTR8, further screening of a mouse genomic library was performed. By analysis of two positive clones, a 109bp and a 57bp sequence, -266 to -374 and -209 to -265, respectively, were located approximately 6.0kb away from each other in the phage clones which were not overlapped with lambda mCTR8. The 3'non-coding region of the mouse ACTH receptor cDNA obtained by 3'-RACE method was contiguous to the coding region by comparing it with the 1.4kb genomic sequence downstream of the ATG. The polyadenylation signal AATAAA was located at the position of 1291 from the ATG. Taken together, the mouse ACTH receptor gene consists of at least 4 exons and three of the exons encoded 5'-untranslated sequences. Moreover, two mRNAs in the presence and absence of the 57bp putative exon 2 generated by alternative splicing were determined by reverse transcription/polymerase chain reaction between putative exon 1 and 4. Finally, the longest cDNA of this gene determined from this experiment was 1707bp while northern analysis revealed approximately 1.8kb mRNA in mouse adrenal gland. It awaits further investigation to clarify the significance of 5'-untranslated non-coding exons and alternative splicing in this receptor gene.

Animals↗
PubMed1996

[Chemotherapy for peritoneal dissemination in gastric cancer under ureteral catheterization].

The treatment of peritoneal dissemination of gastric cancer is mainly chemotherapy, but it use is often limited by ileus, hydronephrosis and jaundice. We employed a ureteral catheter for 6 patients with hydronephrosis due to peritoneal dissemination. Chemotherapy (CDDP + ADM + 5-FU or MTX + 5-FU) was administered in 5 patients. After ureteral catheterization, renal function was kept within normal ranges, so chemotherapy was performed safely. One of five patients became CR and the effect of the treatment was satisfactory (PR: 1, NC: 2). Thus, chemotherapy after ureteral catheterization may be effective for patients with peritoneal dissemination and hydronephrosis.

Adenocarcinoma↗
PubMed1995

Structure-activity relationships of cyclic pentapeptide endothelin A receptor antagonists.

Analogues of the natural product endothelin A (ETA) receptor antagonists cyclo(-D-Trp1-D-Glu2-Ala3-D-Val4-Leu5-) (1) and cyclo(-D-Trp1-D-Glu2-Ala3-D-alloIle4-Leu5-) (2) were prepared and tested for inhibitory activity against [125I]endothelin (ET-1) binding to protein ETA receptors. The DDLDL chirality sequence of the natural products appeared to be critical for inhibitory activity because conversion of either D-Trp or D-Glu (or both) in 1 to the corresponding L-isomer(s) abolished this property. Systematic modifications at each position of the natural products clarified the structure-activity relationships and led to highly potent and selective ETA receptor antagonists. Most replacements of D-Trp1 and Leu5 with other amino acids caused a significant loss of inhibitory activity. In contrast, replacement of D-Glu2 with D-Asp2 enhanced the activity. With regard to the Ala3 position, all analogues with imino acids, independent of being cyclic or acyclic, showed higher affinities than did the amino acid analogues. In addition, most replacements with amino acids, which had various functional groups in their side chains, did not significantly modify ETA binding affinity. The D-Val4/D-alloIle4 position was very important for inhibitory activity, and a beta-position branched D-amino acid or a D-heteroarylglycine was preferable at this position. Among synthesized cyclic pentapeptides, compound 36 (BQ-518) was the most potent ETA receptor antagonist, with a pA2 of 8.1 against ET-1-induced vasoconstriction in isolated porcine coronary arteries. This compound also showed the greatest selectivity between ETA and ETB receptors (IC50 for human ETA = 1.2 nM, IC50 for human ETB = 55 microM). In contrast, compound 8 (BQ-123) is a highly soluble, potent, and selective ETA receptor antagonist (pA2 = 7.4, IC50 for human ETA = 8.3 nM, IC50 for human ETB = 61 microM). The sodium salt of 8 is practically freely soluble in saline. These compounds are useful tools for not only in vitro but also in vivo pharmacological studies.

Amino Acid Sequence↗
PubMed1995

Significance of myeloperoxidase in rapidly progressive glomerulonephritis.

Antineutrophil cytoplasmic autoantibodies (ANCAs) are found in the sera of patients with systemic vasculitis and crescentic glomerulonephritis. We developed monoclonal antibodies against myeloperoxidase (MPO), which is a major perinuclear-ANCA antigen, and examined the presence of MPO in renal tissue from patients with rapidly progressive glomerulonephritis (RPGN) using these monoclonal antibodies. Myeloperoxidase was found in the glomeruli in four of five cases of perinuclear ANCA-positive RPGN, and the distribution pattern was different from that of immunoglobulin G. In perinuclear ANCA-negative crescentic glomerulonephritis, MPO also was detected in two of three cases. Myeloperoxidase was not detected in the capillary walls or mesangium in other nephropathies, such as minimal change disease, membranous nephropathy, and mesangial proliferative glomerulonephritis, or in normal controls. Myeloperoxidase activity was elevated and inversely correlated with the titer of MPO-ANCAs in the sera of perinuclear ANCA-associated RPGN. These data suggest that MPO plays an important role in the glomerular injury of RPGN.

Adult↗
PubMed1995

Electrophysiological demonstration and activation of mu-opioid receptors in the rabbit sinoatrial node.

To investigate the presence of opioid receptors and their physiological role in cardiac pacemaker cells, we studied electrophysiological effects of fentanyl citrate, an activator of the mu-opioid receptors, on the spontaneous action potential (AP) and membrane currents, using small preparations (0.2 x 0.2 x 0.1 mm) of rabbit sinoatrial (SA) node (SAN). Fentanyl (0.1-3 microM) progressively decreased the AP amplitude (APA), maximal rate of depolarization (MRD), and spontaneous firing frequency (SFF) and prolonged the AP duration (APD) and diastolic interval in a concentration-dependent manner. At 1 microM, the spontaneous activity ceased in two of the eight preparations. These actions were blocked by a mu-opioid receptor antagonist, beta-funaltrexamine (beta-FNA), but were not modified by either kappa-opioid receptor antagonist nor-binaltorphimine (nor-BNI), or delta-opioid receptor antagonist ICI-174864. In voltage-clamp experiments using double microelectrode techniques, 1 microM fentanyl reduced the Ca2+ current (ICa) obtained on step depolarization from -40 to 0 mV by 19.9 +/- 9.3% (p < 0.05, n = 5), the fast and slow components of the delayed rectifying K+ current (IKfast, IKslow) tail obtained on repolarization from 10 to -60 mV by 54.7 +/- 4.7 and 41.4 +/- 2.4% (p < 0.05, n = 4), and the hyperpolarization-activated inward current at -90 mV by 12.6 +/- 0.5% (p < 0.05, n = 7), respectively. The gating kinetics of ICa and IKslow were not altered.(ABSTRACT TRUNCATED AT 250 WORDS)

Action Potentials↗
PubMed1995

Coexpression of TGF alpha, epidermal growth factor receptor, and P-glycoprotein in normal and benign diseased breast tissues.

Twenty-four normal or benign breast tissues were examined for the expression of transforming growth factor-alpha (TGF alpha), epidermal growth factor receptor (EGFR), and P-glycoprotein, the product of the mdr-1 gene. Specific staining for all three proteins was observed in the majority of the samples. P-glycoprotein staining was present in most (88%), and confined to the lumenal surface of the ductal epithelium. Membranous EGFR expression was observed in epithelial cells in 92% of the specimens and 42% displayed both myoepithelial and epithelial cell staining. TGF alpha staining was intense and uniformly distributed through the cytoplasm (96%). Coexpression of EGFR, TGF alpha, and P-glycoprotein in normal human breast tissues suggests a role for each of those proteins in normal breast physiology. An interaction may be present in normal breast tissue between the EGF receptor pathway and P-glycoprotein.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1995

[Clinical study of photodynamic therapy for laryngeal cancer].

Photodynamic therapy (PDT) is an innovative treatment involving the use of a photosensitizer and low powered laser to selectively destroy tumor cells. In the head and neck, its application to laryngeal papilloma, metastatic tumor and oral cancer have been reported but our report on PDT for laryngeal cancer is the only clinical report in Japan. At present, we treat laryngeal cancer by PDT using argon and excimer dye lasers such as the HpD. In the present study, we assessed the utility and safety of PDT and investigated long-term prognosis after this therapy. The subjects were 12 patients with laryngeal cancer who underwent PDT between February 1988 and October 1993. Among them, ten with cancer of the vocal cords underwent PDT as the primary treatment and two underwent PDT because of recurrence after radiotherapy. Under local anesthesia, PDT was performed using a video endoscope (Pentax EB2000). The optimal dose from an argon dye laser was set at 200-500 mW/cm2 of continuous waves for 20 minutes and that from the excimer dye laser was set at 200 J/cm2 of pulse waves (3-4 mJ/pulse, 30-40 Hz). The argon dye laser used was the Fujinon PDT developed by Fuji Photo Optical Co., Ltd. The excimer dye laser used was a product of Hamamatsu Photonics Co., Ltd. 1) Effect of PDT The effect of PDT as a primary treatment for ten patients was classified as CR in eight and PR in two cases, the CR rate being 80.0%. When evaluated only for T1 patients, the results were classified as CR in eight and PR in one. The patient whose response was classified as PR had refused repeated PDT. CR was maintained for five and 13 months in the two patients who underwent PDT as a secondary treatment after radiotherapy. CR was obtained in 83.3% of all patients studied. 2) Duration of the effect of PDT and long-term prognosis The patients were followed up for 14 to 71 months. The longest duration of CR achieved by PDT monotherapy was 65 months. Among the patients who underwent PDT as a primary treatment, one developed local recurrence and underwent radiotherapy. However, the prognosis was uneventful in all other patients. CR after PDT monotherapy was maintained for 42 months in one T3 patient. Two patients with a history of previous treatment thereafter relapsed and underwent total laryngectomy. The larynx could be conserved in 83.3% of all patients. However, it could be conserved in 100% of patients who underwent PDT as a primary treatment.(ABSTRACT TRUNCATED AT 400 WORDS)

Aged↗