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Biomedical subjects

K Miyazaki

Publications and source records attributed to K Miyazaki.

At least 271 records · Page 15Linked to original sources

[Intraarterial chemotherapy combined with radiation therapy for advanced cancer of the uterine cervix].

The results of intraarterial chemotherapy (IACT) combined with definitive radiation therapy for 23 advanced and bulky carcinomas of uterine cervix are reported. IA-CT with cisplatin 50 mg and doxorubicin 30 mg was administered by one shot method in bilateral internal iliac arteries. The protocol consisted of one to three treatment session every 3 weeks. Nine of eleven patients with clinical stage III achieved a complete local response (82%), and the 3- and 5-year survival in these cases were 72% and 72%, respectively. These results were superior to the response (58%), 3- and 5-year survivals (68%, 58%) obtained in 19 patients treated mainly with radiation therapy alone. The side effect of grade 2 and 3 for the intestine, such as ileus and hemorrhagic colitis, was noted in 3 patients (15%). In addition, 3 of 8 patients with radical surgery and postoperative radiation therapy after IA-CT developed insufficient fracture of pelvic bone. These complications accompanied by IA-CT combined with radiation therapy and/or surgery increased slightly, compared with that by the previous therapy without IA-CT, but were not critical. The results suggest that IA-CT following radiation therapy is effective to improve the prognosis of patients with Stage III cervical cancer.

Antineoplastic Combined Chemotherapy Protocols↗

Elevated expression of membrane-type 1 and 3 matrix metalloproteinases in rat vascular smooth muscle cells activated by arterial injury.

Matrix metalloproteinases (MMPs) play critical roles in tissue remodeling under various physiologic and pathologic conditions. We recently reported the expression of three membrane-type MMPs (MT-MMPs) by cultured vascular smooth muscle cells (SMCs) of rats (Shofuda et al, 1997). To investigate the roles of the MT-MMPs in the matrix remodeling of blood vessels, expression of MT1-MMP and MT3-MMP was examined in normal and balloon-injured rat carotid arteries by in situ hybridization and immunohistochemistry. Both MT-MMP mRNAs were detected in the intimal-dedifferentiated SMCs, but were negligible in the medial SMCs or in any of normal vascular cells. To elucidate the regulatory mechanism for the MT-MMPs expression, effects of various factors on cultured rat SMCs were also examined. MT1-MMP mRNA was constantly expressed at a high level, and its expression was weakly increased by treatment with interleukin-1beta or tumor necrosis factor-alpha. When the cells were incubated with type IV collagen, the MT1 -MMP expression was markedly decreased. On the other hand, expression of MT3-MMP mRNA was strongly increased by platelet-derived growth factor and fibronectin. These results suggest that type IV collagen may act as a negative regulator for the expression of MT1-MMP in the medial SMCs, whereas platelet-derived growth factor and fibronectin may up-regulate MT3-MMP expression under pathologic conditions. Furthermore, the elevated expression of MT1-MMP and MT3-MMP in SMCs was well associated with their dedifferentiated phenotype.

Animals↗

[Clinical efficacy and reduction effect on prostatic volume of chlormadinone acetate combined with tamsulosin hydrochloride in benign prostatic hyperplasia patients insufficiently treated with tamsulosin hydrochloride only].

Alpha adrenergic blocker has become the first choice in the medical treatment of benign prostatic hyperplasia (BPH). The efficacy of alpha adrenergic blocker has been suggested to be related to the prostatic tissue components, and to be ineffective in treating the clinical symptoms caused by BPH in some cases. The efficacy and prostate reduction of an anti-androgenic agent, chlormadinone acetate, combined with alpha adrenergic blocker, tamsulosin hydrochloride, were evaluated using 40-BPH patients insufficiently treated with tamsulosin hydrochloride alone. Fifty mg of chlormadinone acetate and 0.2 mg of tamsulosin hydrochloride were administered orally once a day for 16 weeks to patients with a prostate subjective symptoms score, I-PSS, of greater than 13 or a peak flow rate of less than 12 ml/s, even after the treatment with 0.2 mg of tamsulosin hydrochloride alone for more than four weeks. Total I-PSS decreased significantly after four weeks. The total irritative symptom score did not change for 16 weeks, but the total obstructive symptom score decreased significantly, as did the total I-PSS. In objective data, the estimated volume of both total prostate and the transition zone on transrectal ultrasonogram decreased significantly at the end of the treatment, and the peak flow rate decreased significantly after 12 weeks. These findings suggest that the addition of chlormadinone acetate may be a reasonable alternative in the treatment of BPH patients responding insufficiently to tamsulosin hydrochloride alone, and that combination therapy using chlormadinone acetate and tamsulosin hydrochloride may be useful for BPH patients with serious obstructive symptoms.

Adrenergic alpha-Antagonists↗

[A case of advanced gastric carcinoma with disappearance of cancer cells by neoadjuvant chemotherapy].

A 74-year-old man was diagnosed by preoperative X-ray and endoscopy with biopsy as having type 2 advanced gastric carcinoma (poorly differentiated adenocarcinoma) in the antrum. CT scan revealed swelling of the paraaortic lymph nodes, which was considered to be metastasis from the gastric carcinoma. As the cancer was judged to be stage IV and too advanced for a curative surgical resection, a neoadjuvant chemotherapy was initiated. One course of the regimen consisted of 10 mg of CDDP (day 1-5, drip) and 300 mg of UFT (day 1-7, oral), and the patient underwent the regimen three times in succession. After the chemotherapy, the swelling of para-aortic lymph nodes disappeared on CT scan. A distal gastrectomy with D2 lymph nodes dissection and sampling of the para-aortic lymph nodes was performed. Histopathological examination revealed that the cancer cells had completely vanished both in the primary tumor and lymph nodes. The effect of this neoadjuvant chemotherapy was judged to be Grade 3 histopathologically.

Adenocarcinoma↗

Single-step isolation method for six glycoforms of human alpha1-acid glycoprotein by hydroxylapatite chromatography and study of their binding capacities for disopyramide.

A single-step isolation method for the glycoforms of human serum alpha1-acid glycoprotein (AAG) using a hydroxylapatite column under a gradient elution program was developed. The concentrations of N-acetylneuraminic acid and monosaccharides (fucose, N-acetylglucosamine, galactose and mannose) of six AAG glycoforms were determined by the pulsedamperometric detection method. For each AAG glycoform, significant sex-related differences in carbohydrate content have been observed only for AAG glycoforms two and six, and not for each AAG glycoform. The relationship between the extent of the branch in the glycan chain and the binding capacity to disopyramide were examined. Female AAG contained highly sialylated AAG glycoforms compared to male glycoforms. Conversely, male AAG was rich in the lower sialylated AAG glycoform. Furthermore, it was found that the drug binding capacity decreases with increasing branching of the glycan chain. This suggests that the binding sites of AAG are hindered by a relatively large carbohydrate moiety, such as tetraantennary structures.

Adult↗

Induction of thioredoxin in human lymphocytes with low-dose ionizing radiation.

Induction of the expression of the thioredoxin (TRX) gene, producing a key protein in regulating cellular functions through redox reaction as well as being a radioprotector, was followed after ionizing irradiation of lymphocytes from human donors. The TRX mRNA level increased to a peak, 5.7-fold higher than the control at maximum, 6 h after irradiation, and then decreased. The optimum radiation dose for enhancement of induction of the TRX mRNA was 0.25 Gy. The TRX protein also increased to a peak, a 3-fold increase at maximum, with the same timing as that for TRX mRNA.

Blotting, Northern↗

Separation methods for glycoprotein analysis and preparation.

Several chromatographic methods have been developed for the isolation and characterization of glycoproteins. In these methods, affinity chromatography, a single-step method, or combined use with general chromatographic methods have now become essential for the purification of many biologically important glycoproteins, including alpha1-acid glycoprotein, immunoglobulins, ceruloplasmin and erythropoietin. On the other hand, almost all glycoproteins exhibit polymorphism associated with their glycan moieties. This feature is wide-spread and has been observed in natural as well as in recombinant DNA glycoproteins. Recently, several sophisticated techniques--such as electromigration method (high-performance capillary electrophoresis) and chromatographic methods (two-dimensional polyacrylamide gel electrophoresis, high-pH anion-exchange chromatography with pulsed-amperometric detection)--have been introduced for qualitative or quantitative estimation of the microheterogeneity of glycoproteins. For gaining further insight into the structure-function relations for microheterogeneity, preparative chromatographic techniques that can yield sufficient quantities of glycoprotein variants must be developed.

Carbohydrate Sequence↗

Expression of matrilysin in vascular endothelial cells adjacent to matrilysin-producing tumors.

Matrilysin is believed to play important roles in tumor progression and metastasis. In the present study, we analyzed matrilysin-producing cells in various human cancer tissues by immunohistochemistry and in situ hybridization. Tumor cells in colorectal carcinomas, pancreatic carcinomas, transitional-cell carcinomas of the kidney and small-cell lung carcinomas were frequently positive for matrilysin. In addition, we found that endothelial cells of arterioles and venules adjacent to matrilysin-positive tumors expressed matrilysin mRNA and protein. The endothelial cells adjacent to matrilysin-negative tumors and those in normal tissues were negative for matrilysin. Furthermore, analyses by casein zymography, Western blotting and RT-PCR showed that matrilysin was weakly expressed by cultured human umbilical vein endothelial cells. Our results suggest that the expression of matrilysin in vascular endothelial cells and in tumor cells may be regulated by common soluble factors, and that endothelial cell-derived matrilysin may contribute to tumor angiogenesis and tumor metastasis.

Animals↗

Expression of trypsin in vascular endothelial cells.

Proteinases produced by vascular endothelial cells are expected to play important roles in many biological processes. Here we report that human vascular endothelial cells express trypsinogen-2 mRNA and its protein product in culture. The trypsinogen production was stimulated by a tumor promoter and associated with cell growth. In situ hybridization analysis showed that the trypsinogen gene was significantly expressed in vascular endothelial cells around gastric tumors and in patients with disseminated intravascular coagulation (DIC). These results suggest the possible roles of endothelial cell-derived trypsin in tumor angiogenesis and abnormal blood coagulation.

Cells, Cultured↗

Expression of three membrane-type matrix metalloproteinases (MT-MMPs) in rat vascular smooth muscle cells and characterization of MT3-MMPs with and without transmembrane domain.

Matrix metalloproteinases (MMPs) produced by rat smooth muscle cells (SMCs) were investigated. SMCs expressed three kinds of membrane-type MMP, MT1-MMP, MT2-MMP, and MT3-MMP, and the MT-MMP expression was stimulated by the presence of serum. MT3-MMP was characterized further by cloning its cDNA. A rat MT3-MMP cDNA encoding 607 amino acids and a cDNA for its transmembrane domainless variant MT3-MMP-del were cloned from a rat SMC cDNA library; a human MT3-MMP cDNA was cloned from a fetal brain cDNA library. Human brain MT3-MMP was similar but not identical to the previously reported human placenta MT3-MMP (94.4% homology). When the MT3-MMP cDNA was expressed in COS-7 cells, endogenous progelatinase A was processed to the mature form. The transfection of rat MT3-MMP-del efficiently converted progelatinase A to the intermediate form but not to the mature one, indicating that the transmembrane domain is important for the complete processing of progelatinase A to maturation. Both MT3-MMP-del and MT3-MMP hydrolyzed gelatin and casein, indicating their broad substrate specificity. Results of experiments with a synthetic MMP inhibitor suggested that MT3-MMP-del and MT3-MMP are rapidly degraded immediately after maturation. The present study suggests that multiple forms of MMPs including MT3-MMP are involved in the matrix remodeling of blood vessels.

Amino Acid Sequence↗

Assignment of human membrane-type matrix metalloproteinase-2 (MT2-MMP) gene to 16q12 by FISH and PCR-based human/rodent cell hybrid mapping panel analysis.

A new group of matrix metalloproteinase with a potential membrane domain was reported as membrane-type matrix metalloproteinases (MT-MMPs), and the gene coding for one of them, MT2-MMP was recently cloned from a human lung cDNA library. To predict its physiological functions by the relation to the genetic disorders mapped on the chromosomes, the chromosomal location of the human MT2-MMP gene was examined by fluorescence in situ hybridization (FISH) and PCR-based analysis with human/rodent hybrid cell mapping panels, and it was assigned to 16q12.

Animals↗

Degradation and utilization of xylans by the rumen anaerobe Prevotella bryantii (formerly P. ruminicola subsp. brevis) B(1)4.

Freshly harvested whole cells from cultures of P. bryantii B(1)4 grown with oat spelt xylan (OSX) as an energy source showed less than 25% of the enzyme activity against OSX, and less than 15% of the activity against birchwood xylan (BWX) and carboxymethylcellulose, that was detectable in sonicated cell preparations. This indicates that much of this hydrolytic activity is either periplasmic, membrane-associated or intracellular and may be concerned with the processing of transported oligosaccharides.P. bryantii B(1)4 cultures were able to utilise up to 45% and 51% of the total pentose present in OSX and BWX, respectively, after 24 h, but could utilize 84% of a water-soluble fraction of BWX. Analysis of the xylan left undegraded after incubation with P. bryantii showed that while xylose and arabinose were removed to a similar extent, uronic acids were utilized to a greater extent than xylose. Predigestion of xylans with two cloned xylanases from the cellulolytic rumen anaerobe Ruminococcus flavefaciens gave little increase in overall pentose utilization suggesting that external P. bryantii xylanases are as effective as the cloned R. flavefaciens enzymes in releasing products that can be utilised by P. bryantii cells. The xylanase system of P. bryantiiis able to efficiently utilise not only xylo-oligosaccharides but also larger water-soluble xylan fragments.

Journal Article↗

Experimental replacement of the thoracic inferior vena cava with a high-porosity expanded polytetrafluoroethylene graft wrapped in an omental pedicle flap.

We examined the patency and healing of a high-porosity expanded polytetrafluoroethylene (ePTFE) graft implanted as an interposition graft in the thoracic inferior vena cava (IVC) and wrapped in an omental pedicle flap. High-porosity ePTFE grafts of 60 microns fibril length, with an internal diameter of 10 mm and a length of 4 cm, were implanted in 12 mongrel dogs. In 6 dogs, the grafts were wrapped in omental pedicle flap, and in the remaining 6 the grafts were unwrapped. The animals were killed 4 weeks after the replacement and the grafts were removed for examination. Patency of the graft in both groups was 100%; however, the thrombus-free area in the omentum-wrapped group was significantly larger (P < 0.05) than that in the unwrapped group. Light microscopy revealed the marked infiltration of cells and capillaries within the graft interstices in the omentum-wrapped group. These findings suggest that encapsulation of the high-porosity ePTFE graft is promoted by an omental pedicle flap.

Anastomosis, Surgical↗

Polypoid adenomyoma of the gallbladder.

We describe a distinctive polypoid lesion of the gallbladder (16 mm in diameter) at the fundus, associated with a granulomatous mass in the liver adjacent to the gallbladder fossa, in a 64-year-old Japanese woman. Preoperatively, the lesion was diagnosed as advanced gallbladder cancer infiltrating the liver, and hepatopancreato-duodenectomy was performed. In the resected specimen, the polyp was round and pedunculate in shape, and, microscopically, it consisted of a mixture of small glandular and surrounding muscular elements, but atypia was not noted. The constituent elements were identical with those of adenomyoma, but the polypoid appearance was unusual. The hepatic lesion proved to be a foreign body granuloma containing multiple barium fragments and giant cells. A deep gastric ulcer, which penetrated into the gallbladder fossa, was also noted, near the granuloma. The histologic features indicate that the polypoid appearance of the tumor was due to a secondary modification of pre-existing adenomyoma by hepatic granuloma. To our knowledge, this is the second reported case of an adenomyomatous lesion of the gallbladder with a polypoid appearance.

Adenomyoma↗