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Biomedical subjects

K Obata

Publications and source records attributed to K Obata.

At least 145 records · Page 8Linked to original sources

Prophylactic chemotherapy with intravesical instillation of adriamycin and oral administration of 5-fluorouracil after surgery for superficial bladder cancer. The Japanese Urological Cancer Research Group for Adriamycin.

The Japanese Urological Cancer Research Group for Adriamycin has conducted a series of clinical trials to investigate the efficacy and safety of prophylactic intravesical chemotherapy for superficial bladder cancer. In the third trial, reported herein, patients with recurrent bladder cancer or multiple primary cancer were selected and randomized to one of four groups using the envelope method after complete resection of the original tumors. Group A was given Adriamycin alone, group B received oral 5-fluorouracil (5-FU), group C was given Adriamycin and oral 5-FU, and group D served as the control group. Of the 544 patients registered, 331 were evaluable for the purpose of this study. The administration of 5-FU (group B) failed to prevent the recurrence of bladder tumors. Although group C (both Adriamycin and 5-FU) did not fare better than group A (Adriamycin only), Adriamycin was effective in preventing the recurrence of tumors, especially in high-risk patients with recurrent and multiple tumors. The risk of recurrence was reduced to 0.21 (95% confidence interval, 0.10-0.44) relative to the control group. There was no indication of a synergistic effect between 5-FU and Adriamycin. As side effects, cystitis syndrome was observed in 23%-30% of the patients in the Adriamycin groups and mild myelosuppression was observed in the 5-FU groups.

Administration, Intravesical↗

Intravenous digital subtraction angiography for the evaluation of renal artery blood flow following the removal of a neuroblastoma.

There have been several reports of acute renal failure following the resection of an abdominal neuroblastoma combined with ipsilateral nephrectomy as well as the atrophy or disappearance of an unresected kidney after tumor resection. Spasms or thrombosis of the renal artery during tumor excision are considered to be the major cause. Since 1989, intravenous digital subtraction angiography (IVDSA) has been used to evaluate the renal artery blood flow immediately following surgery in seven patients with abdominal neuroblastomas. IVDSA was performed using a central venous catheter inserted prior to surgery. In all seven patients, IVDSA provided clear images for the evaluation of renal artery blood flow. In one of the two patients whose kidneys briefly became cyanosed during tumor excision, IVDSA demonstrated an occlusion of the renal artery and prompt measures could be taken to reestablish the blood flow. No complications of IVDSA occurred in any of the seven patients. IVDSA using a central venous catheter was thus considered to be useful for evaluating the renal artery blood flow in patients with a suspected renal artery blood flow disturbance without any risk of complications, and this modality obviated the need for intraarterial angiography.

Abdominal Neoplasms↗

Detection of stromelysin in synovial fluid and serum from patients with rheumatoid arthritis and osteoarthritis.

Stromelysin levels were measured using a one-step sandwich immunoassay in synovial fluid (SF) obtained from 31 patients with rheumatoid arthritis (RA) (31 samples) and 13 patients with osteoarthritis (OA) (13 samples) and in serum from 81 patients with RA (106 samples), 12 with OA (14 samples), 12 with gouty arthritis (gout) (14 samples), and 8 with osteoporosis (OP) (14 samples) to identify differences in the levels in these diseases as well as correlations with clinical parameters in RA. SF stromelysin levels were significantly higher in RA than in OA, and rose with increasing joint destruction in the former. No significant correlations were found between the SF stromelysin level in RA and various clinical parameters, except for the volume of SF which showed a correlation. Serum levels of stromelysin were highest in RA, gout, OA, and osteoporosis in decreasing order, and in RA were correlated with the Steinbrocker Stage. A significant correlation was also found between the serum stromelysin level and number of swollen joints, and correlations with the Lansbury index, ESR, CRP, WBC and Plt. The stromelysin level in SF was thought to be a useful parameter of local joint involvement and that in serum of the severity of systemic joint inflammation.

Aged↗

Increase of tyrosine hydroxylase and its mRNA in the rat substantia nigra pars reticulata by diazepam and picrotoxin.

An involvement of GABAA receptors in the regulation of tyrosine hydroxylase (TH) gene expression in the substantia nigra pars reticulata (SNr) was investigated using immunohistochemistry (IMHC) and nonradioactive in situ hybridization histochemistry (ISH). The number of TH-positive cells was increased for both ISH and IMHC 8 h after a single administration of benzodiazepine diazepam, which facilitates GABAA-receptor-mediated transmission and reduces dopamine release in the substantia nigra (SN). Such increase in TH staining was suppressed when a dopamine D2 receptor agonist quinpirole was administered 10 min after diazepam. Co-administration of diazepam with a dopamine antagonist haloperidol did not further elevate, but rather, reduced haloperidol-induced increases in TH labeling. These results suggest that haloperidol and diazepam regulate TH gene expression in the SNr commonly by depressing dopaminergic transmission, and that diazepam activates TH expression in a group of SNr neurons which express this gene after haloperidol treatment. Moreover, a GABAA receptor antagonist, picrotoxin, activated TH gene expression in the SNr, and diazepam antagonized picrotoxin effects. Since picrotoxin increases neuronal activity, additional mechanisms will operate on TH gene expression. In conclusion, GABAergic substances will activate TH gene expression in SNr neurons (1) through decreasing spontaneous somato-dendritic dopamine release in the substantia nigra and/or (2) by increasing the activity of these neurons.

Animals↗

The toxic effect of Alzheimer amyloid protein precursor overexpressed in the neuroblastoma cell line NB-1 on neurite outgrowth.

The neuroblastoma cell line NB-1 is induced to start neurite outgrowth by dibutyryl cyclic AMP (Bt2cAMP). To study the function of Alzheimer amyloid protein precursor (APP), a stable cell line overexpressing APP was established by cDNA transfection. The APP cDNA was driven by the cytomegalovirus early gene promoter. The transformant underwent degeneration as well as neurite outgrowth in the presence of Bt2cAMP, which also increased the amount of APP mRNA and protein. The expressed APP was mainly processed in the secretory pathway and few amyloidogenic fragments were observed. Hence, not only the beta/A4 protein but also the overexpressed APP itself might be neurotoxic.

Amyloid beta-Protein Precursor↗

[Systematic diagnosis and treatment method for temporomandibular disorders--new chart for primary diagnosis and treatment].

In this study, the classification of temporomandibular disorders of Japanese Society for Temporomandibular Joint was subdivided into ten types for the purpose of connecting directly with treatment, then a new chart for primary diagnosis and treatment were expressed. Ten types, i.e. type I (masticatory muscle disorders), type II (micro traumatic synovitis), type IIIc- (disk disorders except internal derangement; open lock, eminense click and crepitus), type IIIc+ (internal derangement; disc anterior displacement with reduction), type III L (internal derangement; disc anterior displacement without reduction, type IVo (osteoarthrosis with no TMJ symptoms), type IVp (osteoarthrosis with TMJ pain and no disc disorders), type IVc- (osteoarthrosis with crepitus, eminense click and open lock), type IVc+ (osteoarthrosis with internal derangement; disc anterior displacement with reduction), type IV L (osteoarthrosis with internal derangement; disc anterior displacement without reduction) 605 patients who visited our clinic from January 1994 to June 1994 were classified by the new chart for primary diagnosis; type I: 37 cases, type II: 142 cases, type IIIc-:56 cases, type III c+: 215 cases, type III L: 82 cases, type IVo: 8 cases, type IVp: 11 cases, type IVc-: 10 cases, type IV+: 19 cases, type IVL: 25 cases.

Clinical Protocols↗

[Dose intensity in M-VAC chemotherapy with rG-CSF for metastatic transitional urothelial cancer].

The effect of M-VAC (methotrexate, vinblastine, adriamycin and cisplatin) chemotherapy supported recombinant human granulocyte stimulating factor (rG-CSF) was studied in 18 patients with metastatic urothelal cancer. The mean age of the patients was 66 years. Of the patients 6 had lung metastasis and 12 had distant lymph node metastasis. In this study recombinant human granulocyte stimulating factor was administered therapeutically at 100 to 250 micrograms subcutaneously after the white blood cell count was less than 3,000/mm. Relative dose-intensity (RDI) was 0.88 +/- 0.11 and 0.72 +/- 0.19 for 11 patients with rG-CSF and 7 without rG-CSF, respectively. The relative dose regardless of the interval of the cycle of M-VAC chemotherapy (%Dose) was 0.95 +/- 0.06 and 0.86 +/- 0.09 for the patients with rG-CSF and those without rG-CSF, respectively. Of seven patients without rG-CSF 3 patients responded (response rate 42%, mean survival period 7.4 months). Of 11 patients treated with rG-CSF 3 patients responded (response rate 72.7%, mean survival period 20.0 months). Although rG-CSF increased the RDI of M-VAC chemotherapy, the correlation of response with RDI was not clearly demonstrated. The therapeutical administrations of rG-CSF fail to improve the mean white blood cell nadir and to prevent the decrease of the platelet and reticulocyte count.

Aged↗

[Assessment of the pleural cavity with ultrasound and pleurography].

High resolution ultrasonography and ultrasonography guided needle aspiration (UGNA) are useful for the evaluation of pleural lesions. We applied the technique of UGNA for pleurography and were able to see the configuration of the pleural surface and space under physiological conditions. Here we show how these newly developed methods of pleurography and ultrasonography can be used to evaluate changes in pleural configuration and pleural involvement of bronchogenic carcinoma. Newly developed pleurography: A catheter was inserted into the narrow pleural space without making a pneumothorax. After infusion of contrast medium (0.5-1 ml/kg), pleural indentation, adhesions, bullous changes, and partial fusion of lobes were clearly visible. This pleurography is especially useful for the diagnosis of tumor invasion into the pleura and chest wall when the tumor is adjacent to the pleura. Detection of latent malignant pleurisy: Small effusions were detected by ultrasonography in 10% of patients with bronchogenic carcinoma who had no pleural effusion on chest roentgenogram. After UGNA, malignant cells were found in 35% in these tiny effusions (4% of the total). To more accurately assess latent malignant pleurisy, we now perform lavage of the pleural space with 50 ml of saline during pleurography before deciding on surgical treatment.

Adult↗

[A resected case of esophageal leiomyoma with 15 cm in long diameter, diagnosed by transesophageal ultrasonic endoscopy].

A 28-year-old man whose chest X-ray film showed a mass on the right upper mediastinum was admitted. Preoperative examination, including CT, MRI, esophagogram, did not make it possible to determine clinically from which organ the tumor originated. On diagnosing with transesophageal ultrasonic endoscopy (TUE) the tumor was found to originate in the esophageal submucosa, with no involvement of the mediastinal organ apparent. Esophageal sub-mucosal tumor enucleation was performed. The resected tumor was 15 cm in long diameter and weighed 125 g. We therefore believe that TUE is clinically useful in diagnosing the tumor originating in the esophageal wall or adjoining esophageal wall.

Adult↗

Excess of metalloproteases over tissue inhibitor of metalloprotease may contribute to cartilage degradation in osteoarthritis and rheumatoid arthritis.

BACKGROUND: In an attempt to identify the factor(s) involved in the modulation of the degradative pathway of articular cartilage, we previously reported a possible imbalance between the levels of biologically active forms of metalloproteases and tissue inhibitor of metalloprotease (TIMP) in osteoarthritis (OA) cartilage. EXPERIMENTAL DESIGN: We extended our analysis on the protein level and the synthesis of stromelysin-1, collagenase, TIMP-1, and TIMP-2 in normal, OA, and RA cartilages, and provided information on the synthesis pattern of these proteins in respect to the action of interleukin-1 (IL-1). These protein concentrations were determined by specific sandwich EIA assays. RESULTS: This study allowed us to establish that the concentration of stromelysin-1 and collagenase is elevated in both OA and rheumatoid arthritis (RA) cartilages when compared with normal, with significantly higher levels of collagenase found in OA (p < 0.0003) and RA (p < 0.0001), and of stromelysin-1 in RA (p < 0.02). In all cases, the level of stromelysin-1 significantly exceeded (a few 100-fold) the collagenase level. The cartilage TIMP-1 level was notably enhanced only in RA, whereas TIMP-2 was increased in both OA and RA cartilage. RA patients with active disease had a higher level of metalloproteases and TIMP than those patients with inactive disease. Moreover, patients taking steroids alone or in combination with methotrexate had a markedly lower metalloprotease level without any changes in the TIMP-1 level. In culture cartilage explants, the synthesis of stromelysin-1 was enhanced in RA cartilage, whereas the level of collagenase was increased both in OA and RA explants. When compared with normal patients, the TIMP-1 synthesis was essentially unchanged in arthritic explants, whereas the level of TIMP-2 was decreased in RA explants when compared to OA. IL-1 induced a statistically significant increased synthesis of metalloproteases with the highest level found in arthritic explants. IL-1 also significantly decreased the TIMP-1 synthesis in OA and RA explants, and the TIMP-2 synthesis in OA. CONCLUSIONS: This study demonstrates that stromelysin-1 is the predominant metalloprotease synthesized in human articular cartilage and that both TIMP-1 and TIMP-2 are present in this tissue. The differential regulation of metalloprotease and TIMP syntheses by IL-1 suggests that this cytokine, during inflammatory conditions, may promote cartilage degradation by creating an imbalance between the level of these enzymes and their inhibitors.

Aged↗

Prostaglandins E2 and E1 inhibit cytokine-induced metalloprotease expression in human synovial fibroblasts. Mediation by cyclic-AMP signalling pathway.

BACKGROUND: Cytokine modulated matrix metalloprotease (MMP, i.e., collagenase and stromelysin) synthesis may be associated etiologically with osteoarthritic diseases. The aim of this study was to investigate the mode of action by which interleukin-1 beta (IL-1 beta) induced collagenase and stromelysin mRNA expression and synthesis in normal human synoviocytes and to explore mechanisms of suppression of these proteolytic enzymes by prostaglandins (PG). EXPERIMENTAL DESIGN: Collagenase and stromelysin expression and synthesis were induced in cultured human synoviocytes with rhIL-1 beta in the absence or presence of either chemical inhibitors of protein kinase (PK) A and C, PGE2 or PGE1, or cAMP mimetics. We used enzyme immunoassays to determine MMP antigen levels in spent culture medium and Northern hybridization to measure steady-state MMP mRNA expression. RESULTS: Dose-response experiments revealed that 10 pg/ml of interleukin-1 beta was an effective sub-saturating concentration for the induction of collagenase and stromelysin expression in normal human synovial fibroblasts. The rate of collagenase synthesis and expression peaked at 18 to 24 hours after rhIL-1 beta stimulation, whereas stromelysin output increased steadily within the experimental time frame (72 hours). Protein kinase C inhibitors, H-7 and staurosporine, prevented the rhIL-1 beta induction of MMP mRNA expression and protein synthesis. Pretreatment of synoviocytes with phorbol myristate acetate for 18 hours abrogated the ability of rhIL-1 beta to induce MMP synthesis. Prostaglandins E2 and E1 potently inhibited in a dose-dependent fashion rhIL-1 beta induced MMP synthesis: PGE2, IC50, collagenase, 2.3 ng/ml; stromelysin, 21.2 ng/ml; PGE1, IC50, collagenase, 2.5 ng/ml; stromelysin, 13.4 ng/ml. MMP mRNA steady-state levels were suppressed in a fashion similar to that of the protein synthesis. Forskolin, dibutyryl cAMP, and 3-isobutyl-1-methyl xanthine mimicked the effects of the prostaglandins (PGs). [N-(2-methyl-amino)-5-isoquinoline-sulfonamide dihydrochloride] (H-8), an inhibitor of PKA activity, could reverse to a large extent, the suppressive effects of the PGs as did cycloheximide when preincubated with PGE2 before rhIL-1 beta activation of synoviocytes. CONCLUSIONS: We conclude that IL-1 beta stimulates MMP synthesis by activating PKC but not PKA, and that the synthesis of collagenase and stromelysin is discoordinate on a temporal and quantitative basis. PGs inhibit rhIL-1 beta-induced MMP expression and synthesis by virtue of their ability to increase cAMP intracellular levels and subsequent activation of signal transduction mechanisms involving PKA. Homeostasis may be maintained in acute episodes of joint inflammation through feedback processes involving locally produced eicosanoids.

Alprostadil↗

Red blood cell membrane and density changes under ambient and hypoxic conditions in transgenic mice producing human sickle hemoglobin.

Red blood cells (RBC) from patients with sickle cell disease (SCD) are characterized by membrane lesions caused by cell sickling and oxidative damage due to denatured hemichromes. We have developed three lines of transgenic human sickle hemoglobin (Hb S) mice, which produce 30, 50, and 80% human beta sickle globin (h beta S), by crossing transgenic progeny with nonthalassemic, heterozygous, or homozygous beta-thalassemic mice, respectively. Transgenic mice that produce Hb A, developed in a similar fashion, were used as controls. RBC from each transgenic line were examined for pathologic changes. RBC from 50 and 80% h beta S mice sickle upon deoxygenation in vitro while RBC from 30% h beta S mice and all Hb A mice do not. Density gradients of RBC from each Hb S line, including those from 30% h beta S that do not sickle, show broad distributions with increased dense fractions, similar to those of patients with SCD. RBC from Hb S lines exhibit elevated membrane-associated denatured hemoglobin (MADH) levels (0.250 +/- 0.080%) when compared to RBC from nontransgenic (0.073 +/- 0.021%) and transgenic Hb A (0.062 +/- 0.033%) mice. Elevated MADH levels in RBC from the 30% h beta S line suggest that membrane changes occur even though these cells do not sickle. These Hb S-dependent pathologic changes suggest that transgenic Hb S lines may be useful for the study of not only RBC sickling in vivo but also membrane oxidative damage and other chronic changes attributed to abnormal properties of both oxygenated and deoxygenated Hb S.

Anemia, Sickle Cell↗

A facile enzymatic synthesis of cellooligosaccharide derivatives using beta-lactosyl fluoride.

A convenient method for the preparation of cellooligosaccharide derivatives has been developed that uses beta-lactosyl fluoride as the glycosyl donor. The reaction consists of the following enzymatic processes; (1) a cellulase-catalyzed regio- and stereo-selective lactosylation of a beta-cellobioside as the glycosyl acceptor, utilizing the transglycosylating ability of an enzyme-substrate complex formed from beta-lactosyl fluoride and cellulase; (2) beta-D-galactosidase-catalyzed regioselective cleavage of the terminal D-galactose unit from the lactosylated product, giving rise to a beta-cellotrioside derivative. A cellotetraoside derivative has successfully been prepared in a stereo- and regio-selective manner by repeating these enzymatic reactions and using the resulting beta-cellotrioside as starting material.

Carbohydrate Conformation↗

Clinico-pathological studies on a transitional type between extrahepatic biliary atresia and paucity of the interlobular bile ducts.

Among the neonatal and infantile cases of obstructive jaundice seen at Niigata and Yamagata University Hospitals between 1976 and 1990, extrahepatic bile ducts were visualized in 19 cases by either preoperative endoscopic retrograde cholangiopancreaticography (ERCP) or intraoperative cholangiography. Neonatal hepatitis was diagnosed in 3 of these cases by clear images of the bile duct system extending from the common bile duct to the intrahepatic bile duct. In 7 cases, the common bile duct was able to be seen, while the common hepatic duct was only slightly visualized. Four of these 7 cases were consistent with paucity of the interlobular bile ducts (PILBD) based on hepatic histology, while the remaining 3 showed fibrosis, bile ductular proliferation, and many bile plugs in the bile ductuli of the portal areas, concurrent with histological changes in extrahepatic biliary atresia (EHBA), not PILBD. In 9 cases, only the common bile duct was visualized while the common hepatic duct was not seen, 7 of these 9 cases being consistent with type III-a1 EHBA. In 2 cases, neither fibrosis nor proliferation of the bile ductuli was observed in the portal areas, and portal areas without any bile ductuli were also seen, in accordance with findings for PILBD. Three cases which showed similar hepatic histological findings to EHBA despite the presence of patent extrahepatic bile ducts, and 2 cases which had obstructed extrahepatic bile ducts and hepatic histological findings similar to PILBD, were thought to be of a transitional type between EHBA and PILBD.(ABSTRACT TRUNCATED AT 250 WORDS)

Bile Duct Diseases↗

Effects of dietary proteins on linoleic acid desaturation and membrane fluidity in rat liver microsomes.

The effect of dietary protein, casein (CAS) and soybean protein (SOY), on linoleic acid desaturation in liver microsomes was studied in rats. The activity of delta 6 desaturase in total and rough endoplasmic reticula (ER and RER) was significantly higher in the CAS group than in the SOY group. In ER and smooth endoplasmic reticulum, the steady-state fluorescence anisotropy of 1,6-diphenyl-1,3,5-hexatriene, when incorporated into the membrane, was decreased in the SOY group and accompanied by a reduction in the cholesterol/phospholipid (CHOL/PL) ratio, consistent with an increase in membrane fluidity. In a separate study, the effect of varying dietary proteins, CAS, milk whey protein, egg albumin, SOY, potato protein and wheat gluten, on the relationship between the delta 6 desaturase activity and microsomal membrane fluidity was also examined. The results indicated that the dietary protein-dependent change in the liver microsomal CHOL/PL ratio affected membrane fluidity, and subsequently the activity of delta 6 desaturase in liver microsomes. However, since dietary protein influenced the delta 6 desaturase activity in RER without influencing membrane fluidity, it is possible that some regulation might have taken place at the level of enzyme synthesis.

Animals↗

Molecular cloning of a developmentally regulated brain protein, chicken drebrin A and its expression by alternative splicing of the drebrin gene.

Drebrins are developmentally regulated proteins found in the chicken brain and are classified into three forms, E1, E2 and A. Previously we isolated two cDNAs corresponding to the embryonic drebrin mRNAs from a chick embryo cDNA library. They differed in that an internal 129-nucleotide sequence, designated ins1, was inserted in the cDNA encoding drebrin E2 and was deleted in the other cDNA encoding drebrin E1. To search for the cDNA clone encoding drebrin A, a cDNA library of 1-day-old chick brains was screened using embryonic drebrin cDNA fragments as probes. Consequently, a novel cDNA was isolated, the sequence of which was entirely identical with that of drebrin E2 except for the insertion of a 138-nucleotide sequence, designated ins2, in the 5' direction immediately upstream from ins1. Since the translation product of the entire coding region was similar to that of drebrin A, this cDNA should correspond to the mRNA for drebrin A. Sequencing analysis of three drebrin cDNAs clearly indicated that the heterogeneity of chicken drebrins was caused by the insertion or deletion of the two sequences, ins1 and ins2. The amino-terminal half region including ins2 and two short sequences in the carboxyl-terminal region of the predicted drebrin A were highly evolutionarily conserved. Cloning and sequencing of the drebrin gene revealed that ins1 and ins2 were independently encoded by separate exons and three drebrin isoforms were thought to arise by alternative splicing from a single drebrin gene. The difference in the time course of expression and tissue distribution of each drebrin suggests that the machinery of alternative splicing site selection of the drebrin gene is regulated in a developmental stage-dependent and tissue-specific manner.

Alternative Splicing↗

Increased levels of calbindin-D in serum and urine from patients treated by extracorporeal shock wave lithotripsy.

Calbindin-D 28 kDa. is a vitamin D-dependent calcium binding protein that is found mainly in the distal renal tubules and central nervous tissue in humans. Calbindin-D was measured in the serum and urine before, and immediately, 2 hours or 24 hours after extracorporeal shock wave lithotripsy (ESWL*) in 83 consecutive patients. ESWL was performed with the Siemens Lithostar device in 61 patients and with the Dornier MPL9000 lithotriptor in 22. The serum 28 kDa. calbindin-D level was undetectable (less than 20 pg./ml.) in many samples, whereas urinary 28 kDa. calbindin-D could be detected in every sample. The serum 28 kDa. calbindin-D level was usually elevated after ESWL and the concentration in patients treated with the MPL9000 device was greater than in those treated with the Lithostar instrument. Urinary 28 kDa. calbindin-D levels were elevated significantly immediately and at 2 hours after ESWL, and they decreased to the baseline level within 24 hours after ESWL in the Lithostar group but remained consistently significantly elevated after ESWL in the MPL9000 group. This fact may be because the MPL9000 lithotriptor produces a stronger shock wave than does the Lithostar device during ESWL. These results suggest that 28 kDa. calbindin-D is released from damaged distal renal tubule cells into the serum and urine during ESWL and that 28 kDa. calbindin-D is a specific marker for renal damage by ESWL. To our knowledge this is the first clinical study using a sensitive enzyme immunoassay for human 28 kDa. calbindin-D to estimate renal damage during ESWL.

Adult↗