Terminal deletion of chromosome 10q: clinical features and literature review.
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Abnormalities, Multiple↗
Biomedical subjects
T Satoh
Publications and source records attributed to T Satoh.
Analysis of prognostic factors related to primary superficial bladder cancer tumor recurrence in prophylactic intravesical epirubicin therapy.
PURPOSE: The aims of the present study were to examine the effects of intravesical instillation of epirubicin on tumor recurrence and to identify tumors that are at a high risk of recurrence. METHODS: Forty-five patients with primary superficial bladder cancer were treated with prophylactic intravesical epirubicin following transurethral resection of the bladder tumor (TUR-BT). Epirubicin (20 mg) was administered intravesically every second week for 4 months and then once a month or every 2 weeks for next 8 months. Patients were analyzed with respect to prognostic factors related to tumor recurrence. RESULTS: The overall recurrence-free rate, calculated using the Kaplan-Meier method, was 76.1 and 52.3% at 2 and 5 years after operation, respectively. These results were better than those reported for patients treated with TUR-BT alone. A univariate analysis demonstrated that high-grade, T1, sessile, large (> or = 2 cm) and multiple tumors were a significantly high risk for recurrence. A multivariate analysis performed by using the Cox proportional hazard model with stepwise selection showed that morphologic features (pedunculated or sessile) were the most prognostic factors for recurrence. This was followed by age and tumor size. The remaining four factors were not found to contribute significantly to recurrence. CONCLUSIONS: Epirubicin appears to be effective in preventing the recurrence of superficial bladder cancer. Morphologic features, patient age and size of the tumor were considered independent risk factors. The risk of recurrence for each tumor should be taken into consideration when the intravesical adjuvant therapy protocol is being selected.
Administration, Intravesical↗
CNS-specific prostacyclin ligands as neuronal survival-promoting factors in the brain.
Prostacyclin (PGI2) is a critical regulator of the cardiovascular system, via dilatation of vascular smooth muscle and inhibition of platelet aggregation (Moncada, S. 1982, Br. J. Pharmacol., 76, 3). Our previous studies demonstrated that a novel subtype of PGI2 receptor, which is clearly distinct from a peripheral subtype in terms of ligand specificity, is expressed in the rostral region of the brain, e.g. cerebral cortex, hippocampus, thalamus and striatum, and that (15R)-16-m-17,18,19,20-tetranorisocarbacyclin (15R-TIC) and 15-deoxy-16-m-17,18,19,20-tetranorisocarbacyclin (15-deoxy-TIC) specifically bind to the central nervous system (CNS)-specific PGI2 receptor. Here, we report that these CNS-specific PGI2 receptor ligands, including PGI2 itself, prevented the neuronal death. They prevented apoptotic cell death of hippocampal neurons induced by high (50%) oxygen atmosphere, xanthine + xanthine oxidase, and serum deprivation. IC50s for neuronal death were approximately 30 and 300 nM for 15-deoxy-TIC and 15R-TIC, respectively, which well correlated with the binding potency for the CNS-specific PGI2 receptor. 6-Keto-PGF1alpha (a stable metabolite of PGI2), peripheral nervous system-specific PGI2 ligands and other prostaglandins (PGs) than PGI2 did not show such neuroprotective effects. In vivo, 15R-TIC protected CA1 pyramidal neurons against ischaemic damage in gerbils. These results indicate that CNS-specific PGI2 ligands have neuronal survival-promoting activity both in vitro and in vivo, and may represent a new type of therapeutic drug for neurodegeneration.
Animals↗
Ultrastructural features of goat oviductal secretory cells at follicular and luteal phases of the oestrous cycle.
The aim of the present study was to investigate the ultrastructure of secretory cells in the various regions of the goat oviduct during the follicular and luteal phases of the oestrous cycle. During the follicular phase in the fimbriae, the secretory cells contained small secretory granules with electron-dense matrices. In the luteal phase, the secretory granules disappeared and cytoplasmic protrusions, extending beyond the luminal border of the ciliated cells and often containing the nucleus, were predominant. During the follicular phase in ampullary secretory cells, numerous secretory granules with moderately electron-dense matrices were present in the supranuclear cytoplasm and exocytosis of secretory granules was observed. The number of secretory granules was dramatically reduced in the ampullary secretory cells at the luteal phase. Conspicuous cytoplasmic protrusions of secretory cells were observed similar to those of the fimbrial epithelium. Isthmic cells were almost free of secretory granules and lysosome-like bodies were found both at the follicular and luteal phases. In conclusion, our ultrastructural observations of goat oviduct revealed marked cyclic changes in the ultrastructural features of secretory cells and the ultrastructural features and the numbers of secretory granules were distinctive for each particular segment.
Animals↗
IL-4 inhibits the migration of human Langerhans cells through the downregulation of TNF receptor II expression.
The migration of Langerhans cells is an initial event in the sensitization phase of contact sensitivity. Langerhans cells travel from the epidermis to the regional lymph node, and can be variously modulated in the skin where many cytokines are released from epidermal cells, dermal cells, T helper (Th) cells, and other inflammatory cells during the sensitization and elicitation phase of contact dermatitis, and thus induce an altered inflammatory skin reaction. The modulatory effect of the cytokines released in the skin, such as IL-1beta, GM-CSF, and TNF-alpha as epidermal cytokines, IL-2, IL-12, and IFN-gamma as Th1 type cytokines, and IL-4 and IL-10 as Th2 type cytokines, was analyzed using the chemotactic chamber method in this study. Both GM-CSF and TNF-alpha induced the migration of human Langerhans cells in vitro, whereas IL-1beta, IL-2, IL-10, IL-12, and IFN-gamma had no effect on Langerhans cell migration. In contrast, IL-4 inhibited Langerhans cell migration in a dose dependent manner. The inhibitory activity of IL-4 was reversed by both anti-human IL-4 monoclonal antibody and anti-human IL-4 receptor monoclonal antibody. IL-4 inhibited the Langerhans cell migration induced by both TNF-alpha and GM-CSF. Furthermore, anti-TNF-RII monoclonal antibody inhibited both random migration and the migration induced by TNF-alpha, but not that induced by GM-CSF. A reverse-transcriptase-polymerase chain reaction and fluorescence-activated cell sorter analysis revealed that TNF-alpha up-regulated and IL-4 downregulated the TNF receptor II (TNF-RII) expression of Langerhans cells at both the mRNA and the protein levels. The pretreatment of Langerhans cells with TNF-alpha enhanced the migration of Langerhans cells and the expression of TNF-RII. After pretreating Langerhans cells with TNF-alpha, IL-4 inhibited both the migration of Langerhans cells and the expression of TNF-RII in a time dependent manner. These results indicate that IL-4 inhibits the migratory activity of Langerhans cells by downregulating the expression of TNF-RII in human Langerhans cells and thereby modulates the immune response in the skin.
Antibodies, Monoclonal↗
Cutaneous angiosarcoma with thrombocytopenia.
Thrombocytopenia was observed in 3 patients with cutaneous angiosarcoma of the scalp and face. A sudden decrease in the platelet count occurred in association with rapid enlargement of primary or metastatic lesions. Neither antiplatelet antibody nor platelet-associated IgG was detected. Increased serum levels of beta-thromboglobulin and platelet factor 4 indicated that platelets were destroyed and consumed within the vascular bed of the tumor. Prominent PECAM-1 expression on tumor cells may be involved in intratumoral platelet aggregation and consumption. We suggest that the sudden development of profund thrombocytopenia in patients with angiosarcoma may suggest either rapid growth of the primary tumor or herald the development of metastatic disease.
Aged↗
Mammosomatotrophs develop within mammotroph clusters in bovine adenohypophysis.
The existence and distribution of mammosomatotrophs (MS cells) containing growth hormone (GH) and prolactin (PRL) in bovine adenohypophysis were detailed by a combined method of mirror sections and immunohistochemical staining. MS cells always occurred in bovine adenohypophysis but their number was low. In the midsagittal plane, the cells were observed in the hind dorsal, hind ventral and fore ventral region abundant in GH and PRL cells. Whereas, in the zona tuberalis where GH and PRL cells were less frequent, MS cells were not detected. MS cells were invariably solitarily distributed within mammotroph (PRL cell) clusters but not within somatotroph (GH cell) clusters. The proportion of MS cells declined as the ages proceeded and the appearance was spatially related to the arrangement of PRL cells. These findings indicated that, in bovine adenohypophysis, MS cells were differentially distributed and occurred in PRL cell clusters. The results strongly suggest that MS cells originate in GH cells pre-existed within PRL cell clusters with special reference to the functional activation of PRL cells.
Age Factors↗
A case of advanced esophageal cancer showing a long-term complete response with chemotherapy with nedaplatin alone.
We describe a case of advanced esophageal cancer treated successfully by chemotherapy with nedaplatin alone. A 60-year-old male with type 2 advanced esophageal cancer, which was located in the upper part of the esophagus and had invaded adjacent organs, was treated with nedaplatin 150 mg/body (100 mg/m2) given intravenously every 4 weeks from January 6, 1991. He achieved a partial response (PR) and was discharged in March 1991. Subsequently, he received nedaplatin 75 mg/body in an out-patient setting almost every month until August 1992. Toxicities were tolerable and included mild thrombocytopenia and nausea/vomiting. From serial evaluation in October 1993, the esophageal tumor was not observed. After 7 years since initial chemotherapy was administered, he still survives without the disease.
Antineoplastic Agents↗
Primary structure, expression, and site-directed mutagenesis of inorganic pyrophosphatase from Bacillus stearothermophilus.
The complete primary structure of inorganic pyrophosphatase [EC 3.6. 1.1] from Bacillus stearothermophilus (ATCC 12016) was determined at the amino acid level by automated Edman degradation. The subunit of the enzyme consists of 164 amino acid residues with a calculated molecular mass of 18,796. The amino acid sequence of the enzyme is almost identical to that of thermophilic bacterium PS-3. Based on the determined primary structure, a PCR-amplified semi-synthetic gene was constructed and expressed in Escherichia coli JM109. The recombinant Bst. PPase showed the same characteristics and activity as the authentic enzyme, and exhibits higher thermostability than the E. coli enzyme. Furthermore, we prepared tyrosine-substituted variants by site-directed mutagenesis to elucidate the role of two highly conserved tyrosines (Y46 and Y130). As a result, two variants, Y46F and Y130F, lost most of their enzyme activity, whereas their conformations were unaffected. However, the wild-type and two variants exhibited different thermostability behaviors in the presence or absence of Mg2+. Therefore, these tyrosines may contribute to the structural integrity of the active site of the enzyme.
Amino Acid Sequence↗
Hydrophobic interactions of Val75 are critical for oligomeric thermostability of inorganic pyrophosphatase from Bacillus stearothermophilus.
To determine the role of Val75 in the oligomeric structure of trimeric inorganic pyrophosphatase (PPase) [EC 3.6.1.1] from Bacillus stearothermophilus (Bst.), we used site-directed mutagenesis to prepare variants in which Val75 was replaced by Ala, Phe, Leu, Ile, Lys, Gln, and Asp. As a result, the variants in which valine is replaced by hydrophobic residues such as Ala, Phe, Leu, and Ile (V75A, F, L, and I) show almost the same level of enzyme activity and thermostability as the wild type enzyme, whereas variants with hydrophilic residue replacements such as Lys, Gln, and Asp (V75K, Q, and D) showed gross reductions in enzyme activity and thermostability. The dissociation of V75K and V75D from trimer to monomers occurred rapidly as the temperature rose, while V75F, V75L, and V75I dissociated more slowly than the wild type. There was no particular effect of heat treatment on the dissociation of V75A or V75Q, but these variants were slightly dissociated even in the native state. Thus, we conclude that Val75 may locate at the interface between the monomers and its hydrophobic interactions with its surroundings may play a key role in the thermostability and oligomeric subunit interactions of the enzyme.
Enzyme Stability↗
Site-directed mutagenesis of a possible type 1 copper ligand of bilirubin oxidase; a Met467Gln mutant shows stellacyanin-like properties.
In our previous paper, we reported a mutant of recombinant Myrothecium verrucaria bilirubin oxidase, in which the Met467 residue was replaced by Gly [Shimizu, A. et al. (1999) Biochemistry 38, 3034-3042]. This mutant displayed a remarkable reduction in enzymatic activity and an evident decrease in the intensity of the absorption band around 600 nm (type 1 charge transfer transition). In this study, we report the preparation of three Met467 mutants (Met467Gln, Met467His, and Met467Arg) and characterize their enzymatic activities, midpoint potentials, and absorption and ESR spectra. Met467His and Met467Arg show no enzymatic activity and a great reduction in the intensity of the absorption band around 600 nm. Furthermore, their ESR spectra show no type 1 copper signal, but only a type 2 copper signal; however, oxidation by ferricyanide caused the type 1 copper signal to appear. On the other hand, Met467Gln as expressed shows both type 1 and type 2 copper signals in its ESR spectrum, the type 1 copper atom parameters being very different from usual blue copper proteins but very similar to those of stellacyanin. The enzymatic activity of the Met467Gln mutant for bilirubin is quite low (0.3%), but the activity for potassium ferrocyanide is similar (130%) to that of the wild type enzyme. These results indicate that Met467 is important for characterizing the features of the type 1 copper of bilirubin oxidase.
Amino Acid Sequence↗
Deletion of Ala144-Lys145 in Thermus thermophilus inorganic pyrophosphatase suppresses thermal aggregation.
The regions contributing to the thermostability of inorganic pyrophosphatase (PPase, EC 3.6.1.1) from Thermus thermophilus (Tth) were deduced in our previous study by random chimeragenesis, one of them being estimated to be Ala144-Lys145 [Satoh, T., Takahashi, Y., Oshida, N., Shimizu, A., Shinoda, H., Watanabe, M., and Samejima, T. (1999) Biochemistry 38, 1531-1536]. Therefore, we investigated the contributions of these two residues in Tth by preparing a deletion mutant (del.144-145 mutant) of Tth PPase. We examined its thermostability in terms of the CD and fluorescence spectra, and the thermal change in the enzymatic activity. The thermostability of the enzymatic activity of the del.144-145 mutant was similar to that of the wild type Tth PPase, whereas this mutant was more stable against heating. Furthermore, we compared the thermal aggregation of the wild type with that of the del.144-145 mutant. We found that the thermal aggregation of the mutant was reduced relative to that of the wild type. Moreover, the molecular weight of the mutant after heating at 90 degrees C was higher than that of the unheated one, whereas the wild type aggregated under the same conditions. Therefore, we can conclude that although the Ala144-Lys145 residues in Tth PPase may partly cause thermal aggregation, the deletion of these residues may stabilize the Tth PPase molecule structurally against heating and suppress thermal aggregation.
Alanine↗
Regulation of reactive oxygen species by nerve growth factor but not Bcl-2 as a novel mechanism of protection of PC12 cells from superoxide anion-induced death.
Although neurotrophins protect PC12 cells and neurons from oxidative stress-induced death, the molecular mechanism of this effect is largely unknown. Xanthine (XA)+xanthine oxidase (XO) increased the production of the superoxide anion (O2-) and hydrogen peroxide (H2O2), and the death of PC12 cells. Catalase but not superoxide dismutase (SOD) nor a NO scavenger protected PC12 cells from death, indicating that H2O2 is the main effector responsible for this cell death. Both nerve growth factor (NGF) and Bcl-2 protected PC12 cells from O2--induced toxicity. NGF enhanced the production of O2- and suppressed that of H2O2, suggesting that it inhibits the conversion of O2- to H2O2, while Bcl-2 had no such effect. These results suggested that NGF protected the cells from oxidative stress by altering the composition of the reactive oxygen species (ROS) without affecting their total level.
Animals↗
A new UV method for serum gamma-glutamyltransferase assay using recombinant 4-aminobenzoate hydroxylase as a coupling enzyme.
4-aminobenzoate hydroxylase (4ABH) is a flavin-dependent monooxygenase that catalyzes the decarboxylative hydroxylation of 4-aminobenzoate to 4-hydroxyaniline. For use as a clinical reagent, the gene encoding 4ABH from Agaricus bisporus was cloned by the RACE method. Also, the cDNA encoding 4ABH was expressed in Escherichia coli cells as a fusion protein with glutathione S-transferase (GST). The expressed GST-4ABH fusion protein (recombinant 4ABH) in the soluble fraction exhibits decarboxylative hydroxylation and additional NADH oxidation activities.We investigated a new ultraviolet spectrometric method for determining serum gamma-glutamyltransferase (gamma-GT) using recombinant 4ABH as a coupling enzyme. The principle of the method is as follows. Using gamma-glutamyl-3-choloro-4-aminobenzoate (L-gamma-glu-PAClBA) and glycylglycine as the donor and acceptor substrates, 3-choloro-4-aminobenzoate (PAClBA) is formed by the catalysis of serum gamma-GT. PAClBA is stoichiometrically converted to 3-choloro-4-hydroxyaniline (PHClA) and NAD(+) by 4ABH and NADH. However, NADH oxidation results in a high reagent blank, which is considered as a drawback for use as a clinical reagent. Using recombinant 4ABH, we examined the effects of pH and detergents on these two activities, and found that several detergents suppress the additional NADH oxidation activity with little or no effect on hydroxylation activity. The results indicate a promising approach to establishing an ultraviolet spectrophotometric method for determining serum gamma-GT activity using L-gamma-glu-PAClBA as the donor substrate and recombinant 4ABH as a coupling enzyme.
Amino Acid Sequence↗
Molecular cloning, enhancement of expression efficiency and site-directed mutagenesis of rat epidermal cystatin A.
A rat cystatin A cDNA clone was isolated from a lambda ZAP library representing newborn rat skin mRNA by screening with a synthetic oligonucleotide designed from amino acid sequence 15-23 of the cysteine proteinase inhibitor. The obtained clone contained a partial coding region of the inhibitor, lacking the 5'-untranslated region and coding sequence for the NH(2)-terminal 13 residues. The amino acid sequence deduced from the base sequence, Glu14-Phe103, coincided with that determined at the amino acid level. To obtain the recombinant cystatin A protein, the DNA was fused with a synthetic linker encoding its missing N-terminal 17 residues and introduced into an expression vector, pMK2. In Escherichia coli, however, the expression level of the semi-synthetic gene was low, 0. 5 mg of the purified recombinant protein per 1 liter culture being produced. Changing of the codon usage of the N-terminal region in a pET-15b expression system led to an increase in the yield depending on the instability of the putative secondary structure around an initiation codon of the mRNA. The expressed cystatin A showed identical characteristics with the authentic form except for the absence of the N-terminal acetyl blocking group. Using the expression system, two kinds of point mutation, the conservative Val54 in the first loop QxVxG region being changed to Lys and Glu, were introduced, but there was almost no effect on the inhibitory activity toward papain. This suggests that the conserved Val in the reactive site is not restricted and that the hydrophobicity of the position is not essential for the activity of rat cystatin A.
Amino Acid Sequence↗
Differential light regulation of the rbcS gene expression in two cell lines of the liverwort Marchantia paleacea var. diptera.
A cDNA of the small subunit of ribulose-1,5-bisphosphate carboxylase/oxygenase (RuBisCO) gene (rbcS) was isolated from cells of the liverwort Marchantia paleacea var. diptera. The rbcS was expressed light-independently in a green line, but light-dependently in a yellow line. The accumulation of the large subunit of RuBisCO was regulated cooperatively with that of the small subunit.
Amino Acid Sequence↗
Prevention by methylprednisolone of increased circulating tumor necrosis factor-alpha levels and lung injury associated with systemic inflammatory response syndrome due to intraperitoneal hyperthermia.
UNLABELLED: We previously demonstrated that intraperitoneal hyperthermic perfusion (IPHP), which is performed clinically as a treatment for patients with advanced gastrointestinal cancer, can lead to increased serum tumor necrosis factor-alpha (TNF-alpha), systemic inflammatory response syndrome (SIRS), and acute lung injury. Glucocorticoids inhibit the production and actions of TNF-alpha. We investigated whether pretreatment with methylprednisolone (MPS) may modulate serum TNF-alpha and lung injury in patients subjected to IPHP. Serum TNF-alpha was not detected in the patients pretreated with MPS, whereas serum TNF-alpha increased in the control patients (45.7 +/- 8.3 pg/mL, mean +/- SEM) after IPHP. Postoperative lung injury scores were significantly lower in patients pretreated with MPS than in the control patients (P < 0.001). IMPLICATIONS: Pretreatment with methylprednisolone attenuates the increase in circulating tumor necrosis factor-alpha and prevents lung injury in this systemic inflammatory syndrome due to intraperitoneal hyperthermic perfusion.
Adult↗
Primary hepatic lymphoma associated with primary biliary cirrhosis.
We report a case of primary hepatic lymphoma in a 55-yr-old female patient with primary biliary cirrhosis and Sjögren's syndrome. On July 1994, a tumor measuring 11 mm in diameter was detected in the right lobe of the liver by abdominal ultrasonography. A needle biopsy specimen showed the lesion to contain small- and medium-sized lymphoid cells without obvious atypia, and a provisional diagnosis of pseudolymphoma was made. About 2 yr later, the tumor increased to 15 mm in diameter, necessitating a second needle biopsy. Histological and genetic examinations confirmed non-Hodgkin's lymphoma of diffuse, mixed small and large cell, B-cell type. However, the size of the tumor remained almost stable (16 mm in diameter) over a period of 7 months after diagnosis, without any treatment for lymphoma, indicating a low grade malignancy. We document hepatic lymphoma as an additional complication of primary biliary cirrhosis.
Adult↗