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Biomedical subjects

M Maruyama

Publications and source records attributed to M Maruyama.

At least 127 records · Page 7Linked to original sources

A neurological disease caused by an expanded CAG trinucleotide repeat in the TATA-binding protein gene: a new polyglutamine disease?

To investigate whether the expansion of CAG repeats of the TATA-binding protein (TBP) gene is involved in the pathogenesis of neurodegenerative diseases, we have screened 118 patients with various forms of neurological disease and identified a sporadic-onset patient with unique neurologic symptoms consisting of ataxia and intellectual deterioration associated with de novo expansion of the CAG repeat of the TBP gene. The mutant TBP with an expanded polyglutamine stretch (63 glutamines) was demonstrated to be expressed in lymphoblastoid cell lines at a level comparable with that of wild-type TBP. The CAG repeat of the TBP gene consists of impure CAG repeat and the de novo expansion involves partial duplication of the CAG repeat. The present study provides new insights into sporadic-onset trinucleotide repeat diseases that involve de novo CAG repeat expansion.

Adolescent↗

Hepatocyte growth factor concentrations are elevated in peritoneal fluid of women with endometriosis.

The concentrations of hepatocyte growth factor (HGF) in peritoneal fluid (PF) from women with endometriosis (n = 36) and without endometriosis (n = 40) were measured. All of the PF samples examined contained detectable concentrations of HGF. The HGF concentrations in PF from women with stage III/IV endometriosis (0.906 ng/ml, 0. 561-1.185; median, interquartile range) were significantly higher (P < 0.0001) than those from women without endometriosis (0.315 ng/ml, 0.251-0.472). The HGF concentrations from women with stage I/II endometriosis (0.417 ng/ml, 0.310-1.023) appeared to be intermediate. There were no apparent variations detected among the HGF concentrations in women in the follicular or luteal phases regardless of the presence of endometriosis. Interestingly, HGF concentrations in PF from women on gonadotrophin releasing hormone analogues, independent of the presence of endometriosis, were comparable with those from untreated women. Given the known mitogenic property of HGF in human endometrial cells, these results suggest that HGF might play a role in the progression of endometriosis.

Adult↗

Tumor markers CEA, CA19-9 and CA125 in monitoring of response to systemic chemotherapy in patients with advanced gastric cancer.

BACKGROUND: To evaluate whether tumor markers can be used to assess response to systemic chemotherapy, we analyzed preliminarily the relationship between the response to chemotherapy based on serial imaging and on change in serum tumor marker level of CEA, CA19-9 and CA125. METHODS: We analyzed 26 patients with advanced gastric cancer in whom at least one of the tumor markers CEA, CA19-9 and CA125 was elevated before systemic chemotherapy with regard to the relationship between the change in serum tumor marker level and response assessment by imaging studies throughout the treatment course. A responder was defined as showing a > or = 50% drop in tumor marker level for more than 4 weeks. RESULTS: The sensitivity and negative predictive value of falling tumor marker level after chemotherapy for a partial response in imaging was 100%. When patients were categorized as responders or non-responders, a significant correlation was observed between the assessment of response by tumor markers and by imaging studies. The survival time of responders assessed by tumor markers was significantly longer than that of non-responders. CONCLUSIONS: The measurement of tumor markers might be useful in monitoring response and in predicting the prognosis of patients with advanced gastric cancer treated with systemic chemotherapy. Tumor markers may be used as a means of monitoring treatment in patients when in an imaging study it is difficult to assess response to chemotherapy in clinical practice. Further studies are required to confirm these findings.

Adult↗

Crystallization and preliminary X-ray diffraction studies of bleomycin-binding protein encoded on the transposon Tn5.

A bleomycin-binding protein, designated BLMT, encoded on the transposon Tn5 was crystallized using the vapour-diffusion method in a form suitable for X-ray diffraction analysis. Crystals were grown at pH 6.5 in 0.1 M sodium cacodylate and 0.2 M calcium acetate, using 25% PEG 6000 as a precipitant. They belong to the orthorhombic system, space group C2221, with unit-cell dimensions a = 81.56, b = 85.25, c = 78.91 A and one dimer in the asymmetric unit. The diffraction intensity data were collected on beamline 18B of the Photon Factory to 2.0 A resolution with a merging R value of 0.052. The diffraction data set is 91% complete.

Acetyltransferases↗

Reactive oxygen intermediates stimulate interleukin-6 production in human bronchial epithelial cells.

Reactive oxygen intermediates (ROIs) play an important role in the initiation and progression of lung diseases. In this study, we investigated whether ROIs were involved in the induction of interleukin (IL)-6 in human bronchial epithelial cells. We exposed normal human bronchial epithelial cells as well as a human bronchial epithelial cell line, HS-24, to ROIs. We measured the amount of IL-6 in the culture supernatants using ELISA and the IL-6 mRNA levels using RT-PCR. Superoxide anions (O-2), but not hydrogen peroxide (H2O2), increased IL-6 production. To examine whether it is a cell type-specific mechanism of airway epithelial cells, the experiments were also performed in human lung fibroblasts, WI-38-40. In WI-38-40 cells, neither O-2 nor H2O2 increased IL-6 production. In contrast, tumor necrosis factor (TNF)-alpha (200 U/ml) induced IL-6 at the protein and mRNA levels in both airway epithelial cells and lung fibroblasts. This cytokine-induced IL-6 production was significantly suppressed by several antioxidants, including dimethyl sulfoxide (DMSO), in airway epithelial cells. In WI-38-40 cells, DMSO was not able to suppress IL-6 production induced by TNF-alpha. Pretreatment with DMSO recovered the TNF-alpha-induced depletion of intracellular reduced glutathione in HS-24 cells. These findings indicate that oxidant stress specifically induces IL-6 production in human bronchial epithelial cells and that in these cells ROIs may be involved in IL-6 production after stimulation with cytokines such as TNF-alpha. Presumably, ROIs participate in the local immune response in lung diseases via IL-6 release from bronchial epithelial cells.

Antioxidants↗

Immunocytochemical localization of prolactin-releasing peptide in the rat brain.

A hypothalamic peptide that stimulates PRL release has recently been found as a ligand of an orphan receptor and named PRL-releasing peptide (PrRP). PrRP and its receptor were mainly detected in the hypothalamus and pituitary gland, respectively. Its characteristics suggested PrRP to be a novel hypophysiotropic peptide that stimulates the anterior pituitary PRL cell; however, this remained to be confirmed morphologically. We therefore performed an immunocytochemical study to locate PrRP in the rat brain using the region-specific monoclonal antibodies, P2L-1C and P2L-1T, which recognize the C-terminal and the internal sequence of PrRP, respectively. Our results clearly show that dense immunoreactive nerve fiber networks are present in the paraventricular hypothalamic nucleus, supraoptic nucleus, paratenial thalamic nucleus, basolateral amygdaloid nucleus, and bed nucleus of the stria terminalis. A small number of PrRP nerve fibers was also observed in the neural lobe of the hypophysis. However, no immunopositive fiber was observed in the external region of the median eminence, which is known to be the release site of the classical hypophysiotropic hormones. Also, the distribution of PrRP was not changed during the estrous cycle. We therefore concluded that PrRP probably differs from classical hypothalamic releasing hormones. We found the immunoreactive cell bodies to be mainly in the caudal portion of the dorsomedial hypothalamic nucleus and solitary nucleus. A double immunocytochemical procedure revealed that some PrRP-positive neurons showed synaptic contact with oxytocin-positive cell bodies in the paraventricular hypothalamic nucleus, which suggests that PrRP regulates the function of oxytocin neurons. This is the first report to demonstrate the localization of the novel hypothalamic peptide, PrRP, and we therefore suggest that it takes part in a variety of brain functions. However, it is not yet known how PrRP is transported to the pituitary gland, which is the site that contains the greatest concentration of receptors to this new peptide. Therefore, additional work will be required to resolve this discrepancy between ligand and receptor site location.

Animals↗

Analysis of carbohydrate residues on recombinant human thyrotropin receptor.

An investigation of the sugar groups on recombinant human TSH receptors (TSHR) expressed in CHO-K1 cells and solubilized with detergents is described. Western blotting studies with TSHR monoclonal antibodies showed that the receptor was present principally as two bands with approximate molecular masses of 120 and 100 kDa. Further blotting studies using lectins and/or involving treatment with different glycosidases indicated that the 100-kDa band contained about 16 kDa of high mannose-type sugars, and the 120-kDa band contained about 33 kDa of complex-type sugars. It was possible to separate the 120- and 100-kDa components of the TSHRs by lectin affinity chromatography. In particular, Galanthus nivalis lectin, which binds high mannose-type sugars, bound the 100-kDa band, but not the 120-kDa band, whereas Datura stramonium lectin, which binds complex-type sugars, bound the 120-kDa band, but not the 100-kDa band. 125I-Labeled TSH binding studies with the various lectin column fractions showed that TSH-binding activity was principally associated with the complex-type sugar containing the 120-kDa form of the receptor rather than the high mannose-containing 100-kDa form. During peptide chain glycosylation, high mannose-type sugar residues are attached first and then modified by the formation of complex type structures to form the mature glycoprotein. Our data suggest that in the case of the TSH receptor, this type of posttranslational processing has an important role in forming the TSH-binding site.

Animals↗

Preparation and characteristics of antibacterial sepiolite containing povidone-iodine as a useful pharmaceutical product for patient care.

Povidone-iodine (PVP-I), an antibacterial medicine, was infiltrated in sepiolite (SPL). The available iodine content in this new pharmaceutical product, a sepiolite preparation containing povidone-iodine (PVP-I-SPL), was retained at 98.9 and 98.3% during storage at 40 degrees C for 3 and 6 months, respectively. The effective removal of various gasses, including ammonia, hydrogen sulfide, ethylmercaptan and acetaldehyde, was achieved by use of PVP-I-SPL. Especially, the concentration of ammonia gas was reduced more than half after 30 min of exposure, suggesting that PVP-I-SPL has excellent ability to adsorb ammonia gas. The satisfactory antibacterial effect of PVP-I-SPL was also obtained by testing its minimum bactericidal concentration (MBC). No irritation reactions to the rabbit auricle or ophthalmic mucosa or to human skin were observed by the skin irritation test. The PVP-I-SPL preparation has bactericidal activity and gas-adsorbing ability; therefore, this pharmaceutical product should be useful for the prevention of infections and deodorization in hospital rooms and houses, as well as in nursing homes for elderly people.

Absorption↗

Intestinal blockage by carcinoma and Blastocystis hominis infection.

We detected heavy infections of Blastocystis hominis in four individuals with intestinal obstruction due to cancerous growths. After surgery, the infections spontaneously resolved, without specific chemotherapy. It appears that the B. hominis infection was coincidental and not related to the neoplastic growth. We suggest that intestinal obstruction and concomitant stool retention, plus hemorrhage from cancerous lesions, may have permitted the more abundant growth of B. hominis. This is the first report of a possible relationship between intestinal obstruction and a concomitant B. hominis infection.

Adolescent↗

[Experimental study on intraperitoneal administration of 5-fluorouracil for liver metastasis in comparison with intravenous administration].

We studied the effects of 5-fluorouracil intraperitoneal administration using mouse liver metastasis model. We inoculated 50 microliters Colon26 cell suspension into the spleen and resected it 15 min after cell inoculation under general anesthesia with Ketamine. Control group (n = 7) had no treatment. The intraperitoneal (i.p.) group (n = 8) and intravenous (i.v.) group (n = 7) underwent the treatment on the 2nd and 4th day after the operation. Experimental chemotherapies consisted of 1.5 ml 5-fluorouracil solution (50 mg/kg) for i.p. group and 0.2 ml 5-fluorouracil solution (50 mg/kg) for i.v. group. On the 14th day after the cell implantation, necropsies were performed. Deposits on mouse livers were counted and the mouse livers weighted. Counting of metastatic liver deposits revealed the number of deposits in the control group was 25.6 +/- 12.9, against 2.9 +/- 1.9 and 16.0 +/- 15.6, in the i.p. and i.v. group, respectively. Significant differences in the number of liver deposits were obtained between the control group and i.p. group, and between i.p. group and i.v. group (p < 0.05). The mean liver weight (mg)/mouse body weight (g) were 76.3 +/- 24.7 in the control group, 54.3 +/- 4.7 in the i.p. group and 60.0 +/- 12.7 in the i.v. group. A significant difference was observed only between the control group and the i.p. group (p < 0.05). I.p. administration of 5-fluorouracil was superior to i.v. administration for control of the liver metastasis. Moreover, the side effect by 5-fluorouracil i.p. treatment was milder than by i.v. therapy. We confirmed the effectiveness of 5-fluorouracil intraperitoneal chemotherapy for the potential liver metastasis and liver micrometastasis. Intraperitoneal chemotherapy is also useful for peritoneal seeding. We think intraperitoneal chemotherapy is a recommendable administration route for gastrointestinal malignancies.

Animals↗

[Estimation of antibacterial activity of various antibiotics against Pseudomonas aeruginosa by score method].

Antibacterial activity of various antibiotics against Pseudomonas aeruginosa isolated from each hospitals depends on the variety or amount of antibiotics used in each hospital. The antibiotic, which is effective to P. aeruginosa in a certain hospital is not always effective to that in other hospital. The excellent antibiotics in antibacterial activity have low MIC and hard to progress in resistance, and such antibiotics may be effective against P. aeruginosa isolated from any hospitals. Therefore we thought that the antibiotic, which was progress to resistance, would show a great difference in MIC among hospitals, and we investigated MIC and difference of MIC of various antibiotics against P. aeruginosa isolated from six hospitals. Furthermore, we converted the data of MICs and difference of MIC among six hospitals into the score, and tried to estimate antibacterial activity of various antibiotics by using those scores. From the results of analysis in this report, we think the antibiotics actually surpass in antibacterial activity may be imipenem, cefozopran, cefsulodin and amikacin. New analytical method proposed in this report will become one of potential methods to estimate antibacterial activity of antibiotics against bacteria isolated from inpatient with bacterial infections.

Anti-Bacterial Agents↗

[Experimental study on intraperitoneal and intravenous administration of anti-tumor agents for liver metastasis].

Intraperitoneal chemotherapy has been the treatment for peritoneal seedings. Most of the anti-tumor agent administered intraperitoneally is absorbed from visceral peritoneum, gets into the portal vein system and reaches the liver. Theoretically, intraperitoneal administration of anti-tumor agents must show equivalent effects on the liver metastasis to portal vein infusion. We compared the efficacy of intraperitoneal and intravenous administration of 5-FU, CDDP and CPT-11, using colon 26 mouse liver metastasis model. Intraperitoneal administration of 5-FU or CPT-11 was statistically superior to intravenous administration to diminish the liver metastatic deposits. CDDP experiment did not show a statistical difference, but the superiority intraperitoneal administration was recognized. Intraperitoneal administration of anti-tumor agents is more effective for not only peritoneal seedings but also liver metastases than intravenous administration. Intraperitoneal chemotherapy might be an effective adjuvant chemotherapy for gastrointestinal malignancies.

Animals↗

[Pharmaco-dynamic study of methotrexate (MTX) during intraperitoneal MTX/5-FU sequential therapy after gastric surgery].

A pharmaco dynamic study of Methotrexate (MTX) during intraperitoneal MTX/5-FU sequential therapy was carried out after gastric surgery. A comparative study of the route of MTX administration and its dose was also done. 1) Comparative study of the serum concentration of MTX between i.p. and i.v. administration revealed a similar MTX concentration except immediately after administration. 2) A comparative study of the serum concentration of MTX administered i.p. between patients with and without malignant ascites was conducted. Immediate elevation of the serum concentration of MTX was observed in patients without malignant ascites. On the other hand, the MTX concentration was slowly elevated and washed out in patients with malignant ascites. 3) The MTX concentration in the intraperitoneal fluid was compared between patient with and without malignant ascites. In patients without malignant ascites, MTX disappeared quickly from the intraperitoneal fluid. However, the MTX concentration lasted long in the malignant ascites cases. These results were similar with a low-dose MTX (30 mg/body) or moderate dose (100 mg/body). MTX/5-FU sequential i.p. therapy can thus be an effective treatment for patients after gastric surgery, though clearance of MTX was slow in cases with malignant ascites.

Combined Modality Therapy↗

[Intrabiliary administration of doxorubicin for pancreaticobiliary cancer].

UNLABELLED: The effect and drug absorbtion of intrabiliary chemotherapy with Doxorubicin for pancreaticobiliary cancer with PTCD was investigated. Doxorubicin (DXR: 20 mg) was administered intrabiliary for 3 hours by PTCD catheter. Radiographic evaluation of the bile duct before and after chemotherapy and measurement of DXR concentration in the serum and bile were carried out. RESULTS: Intrabiliary administration of DXR was completed without any significant complications other than epigastric pain. Radiographic study of the bile duct of a patient with pancreatic cancer who could successfully complete DXR administration showed improvement of bile duct passage. The placement of biliary stent could be achieved. Concentration of DXR in the serum after administration was below the lowest determinable level while those in the bile maintained a considerably high concentration 4 hours after the administration. With negligible absorption from bile, intrabiliary chemotherapy with DXR was thought to be an acceptable palliative treatment for pancreaticobiliary cancer.

Aged↗

[Experimental trials of temporary insertion of removable catheter into artery for postoperative prophylactic hepatic arterial infusion chemotherapy].

We often experience hepatic metastases after resections for advanced gastrointestinal cancers. Various methods such as resection and hepatic arterial infusion chemotherapy are used when a metastatic tumor is detected on imagings. We have considered postoperative prophylactic hepatic arterial infusion chemotherapy for the prevention of heterochronous hepatic metastases. For this purpose, we conducted experimental trials of temporary insertion of a catheter, which we would be able to remove safely in the near future, into an artery. Laparotomy was done on rabbits under general anesthesia, and a 16 G catheter was inserted into the left renal artery. The proximal site of the artery and the catheter were ligated together with Elastik, and the catheter was fixed with coated VICRYL RAPIDE distal of the insertion point. Upon insertion of the catheters, there was no bleeding, and neither occlusion nor dislocation of the catheter occurred. Two weeks later, the catheters were easily removed without bleeding under laparotomy. At a second-look laparotomy after 2 more weeks, there were no abnormal findings such as hematomas. Therefore, we concluded that our method would be acceptable for the temporary catheter insertion into an artery which could be removed safely and easily when the chemotherapy was finished.

Animals↗

[Liver concentration of CPT-11, SN-38 and SN-38 GLU in intraperitoneal and intravenous administration of CPT-11].

Our previous mouse experiment showed intraperitoneal administration of CPT-11 was more effective not only for peritoneal seeding but for liver metastases than intravenous administration of CPT-11. We studied tissue concentrations of the liver when CPT-11 was administered intraperitoneally or intravenously for ICR mice. Mice liver was resected at 15 min, 1, 2, 4, 8 and 26 hours after intraperitoneal or intravenous administration of 40 mg/kg CPT-11. CPT-11, SN-38 and SN-38 GLU were measured with HPLC. The liver concentration of CPT-11 at 15 min after intravenous administration was higher than after intraperitoneal administration. A higher liver CPT-11 concentration was prolonged in the intraperitoneal administration group. No differences were demonstrated in the concentrations of SN-38 and SN-38 GLU between i.p. and i.v. groups.

Animals↗

[Hemodynamics at hepatoarterial infusion of 5-FU in a chronic renal failure patient maintained by hemodialysis].

The authors studied the hemodynamics of 5-FU hepatoarterial infusion in a colorectal cancer patient with multiple liver metastases, who had chronic renal failure maintained by hemodialysis. Under weekly high dose 5-FU hepatoarterial infusion (1,000 mg/m2, 5 hours), on a non-dialysis day, serum 5-FU concentration was 1,090 ng/ml just after the 5 h infusion, 391 ng/ml at 15 min, 217 ng/ml at 30 min, 47 ng/ml at 60 min, and < 4 ng/ml at 120 min after infusion. On a dialysis day it was 1,500 ng/ml just after infusion, 41 ng/ml at 15 min, 5 ng/ml at 30 min, and < 4 ng/ml at 60 and 120 min after infusion. A control group (n = 4), who had liver metastases from colorectal cancers and normal renal functions, showed 5-FU serum concentration of 987 +/- 384 ng/ml just after infusion, 226 +/- 117 ng/ml at 15 min, 18.5 +/- 5.8 ng/ml at 30 min, < 4 ng/ml at 60 and 120 min after infusion. The serum 5-FU concentration of the patient was maintained higher on non-dialysis days, while it decreased more rapidly on dialysis days than that of the control group. There were no clinical complications due to the weekly high dose 5-FU hepatoarterial infusion. Under the treatment of continuous 5-FU hepatoarterial infusion (500 mg/day), the serum 5-FU concentration of this patient was kept under 115 ng/ml. After hemodialysis, the concentration decreased. The serum 5-FU concentration of the control group (n = 4) was under 66 ng/ml. There were no side effects under the protocol of continuous 5-FU hepatoarterial infusion. 5-FU hepatoarterial infusion for liver metastasis was a safe treatment for a renal failure patient with hemodialysis.

Aged↗