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Biomedical subjects

M Kuroda

Publications and source records attributed to M Kuroda.

At least 109 records · Page 6Linked to original sources

Saundersiosides C-H, rearranged cholestane glycosides from the bulbs of Ornithogalum saundersiae and their cytostatic activity on HL-60 cells.

Six novel rearranged cholestane glycosides with a six-membered hemiacetal ring system, designated as saundersiosides C-H, were isolated from the bulbs of Ornithogalum saundersiae. Their structures were determined on the basis of spectroscopic analysis and the result of hydrolysis. The conformation of the six-membered hemiacetal ring of the rearranged cholestanes was shown to be almost a boat-form by molecular mechanics and molecular dynamics calculation studies. Among the isolated compounds, saundersioside E, F, G and H with an aromatic acid ester group at the glycoside moiety were found to be highly cytostatic to human leukemia HL-60 cells, showing IC50 values of 0.021, 0.019, 0.063 and 0.052 microM, respectively, which are as potent as those of the clinically applied anticancer agents, etoposide and methotrexate.

Antineoplastic Agents, Phytogenic↗

Cholestane rhamnosides from the bulbs of Ornithogalum saundersiae.

Phytochemical examination of the bulbs of Ornithogalum saundersiae yielded six cholestane rhamnosides, two of which had previously been isolated from the same plant material. However, detailed spectroscopic analysis of the aglycone led us to revise the configuration of the C-11 hydroxyl group of the latter two and reassign their structures as (22S)-cholest-5-ene-3 beta,11 alpha,16 beta,22-tetrol 16-O-alpha-L-rhamnopyranoside and (22S)-cholesta-5,24-diene-3 beta,11 alpha,16 beta,22-tetrol 16-O-alpha-L-rhamnopyranoside, respectively. The other four are new naturally occurring constituents and their structures were determined to be (22S)-cholest-5-ene-3 beta,11 alpha,16 beta,22-tetrol 16-O-(2,3-di-O-acetyl-alpha-L-rhamnopyranoside), (22S)-cholest-5-ene-3 beta,11 alpha,16 beta,22-tetrol 16-O-{2-O-acetyl-3-O-(3,4,5-trimethoxybenzoyl)-alpha-L-rhamnopyran oside}, (22S)-cholest-5-ene-3 beta,11 alpha,16 beta,22-tetrol 16-O-{2-O-acetyl-3-O-(p-methoxybenzoyl)-alpha-L-rhamnopyranoside} and (22S)-cholesta-5,24-diene-3 beta,11 alpha,16 beta,22-tetrol 16-O-(2,3-di-O-acetyl-alpha-L-rhamnopyranoside), respectively. The isolated compounds were evaluated for their cytostatic activity against leukemia HL-60 cells.

Carbohydrate Conformation↗

Steroidal glycosides from the bulbs of Allium jesdianum.

Phytochemical analysis of the fresh bulbs of Allium jesdianum yielded four steroidal glycosides, (22S)-cholest-5-ene-1beta,3beta, 16beta,22-tetrol 1,16-di-O-beta-D-glucopyranoside (1), (22S)-cholest-5-ene-1beta,3beta,16beta,22-tetrol 1-O-alpha-L-rhamnopyranosyl 16-O-beta-D-glucopyranoside (2), (25R)-5alpha-spirostane-2alpha,3beta-diol 3-O-[O-beta-D-glucopyranosyl-(1-->2)-O-[beta-D-xylopyranosyl-(1-->3)] -O-beta-D-glucopyranosyl-(1-->4)-beta-D-galactopyranoside] (F-gitonin) (3), and (25R)-5alpha-spirostane-2alpha,3beta, 6alpha-triol 3-O-[O-beta-D-glucopyranosyl-(1-->2)-O-[beta-D-xylopyranosyl-(1-->3)] -O-beta-D-glucopyranosyl-(1-->4)-beta-D-galactopyranoside] (4). Compound 2 is a new natural product, and 4 is a new spirostanol saponin. Compound 3 was found to exhibit cytostatic and cytotoxic activities against several malignant tumor cells.

Allium↗

Triterpene saponins and lignans from the roots of Pulsatilla chinensis and their cytotoxic activity against HL-60 cells.

Two new triterpene saponins (8 and 9) and seven previously reported triterpene saponins (1-7) based upon oleanolic acid or hederagenin, along with two known lignans, (+)-pinoresinol (10) and beta-peltatin (11), were isolated from a saponin fraction prepared from the MeOH extract of the roots of Pulsatilla chinensis. The structures of the new saponins were determined by spectroscopic analysis, including 2D NMR spectroscopic techniques, and the results of hydrolytic cleavage. The isolated compounds and some derivatives were evaluated for their cytotoxic activity against HL-60 human leukemia cells.

Antineoplastic Agents, Phytogenic↗

Two-dimensional electrophoresis of Malassezia allergens for atopic dermatitis and isolation of Mal f 4 homologs with mitochondrial malate dehydrogenase.

The yeast Malassezia furfur is a natural inhabitant of the human skin microflora that induces an allergic reaction in atopic dermatitis. To identify allergens of M. furfur, we separated a crude preparation of M. furfur antigens as discrete spots by 2-D PAGE and detected IgE-binding proteins using sera of atopic dermatitis patients. We identified the known allergens, Mal f 2 and Mal f 3, and determined N-terminal amino acid sequences of six new IgE-binding proteins including Mal f 4. The cDNA and genomic DNA encoding Mal f 4 were cloned and sequenced. The gene was mitochondrial malate dehydrogenase and encoded Mal f 4 composed of 315 amino acids and a signal sequence of 27 amino acids. We purified Mal f 4, which had a molecular mass of 35 kDa from a membrane fraction of a lysate of cultured cells. Thirty of 36 M. furfur-allergic atopic dermatitis patients (83.3%) had elevated serum levels of IgE to purified Mal f 4, indicating that Mal f 4 is a major allergen. There was a significant correlation of the Phadebas RAST unit values of Mal f 4 and the crude antigen, but not between Mal f 4 and the known allergen Mal f 2.

Allergens↗

Primary low-grade gastric mucosa-associated lymphoid tissue (MALT) lymphoma with polypoid appearance. Polypoid gastric MALT lymphoma: A clinicopathologic study of eight cases.

In the current study, we report eight cases with primary low-grade gastric mucosa-associated lymphoid tissue (MALT) lymphoma endoscopically characterized by polypoid lesions in order to highlight their clinicopathologic significance. Four patients were male, their ages ranging from 40 to 78 years old. The resected specimens revealed a histology of low-grade MALT lymphoma characterized by dense lymphocytic infiltration predominantly in the submucosa and a relatively monotonous proliferation of centrocyte-like cells with reactive follicles and infrequent lymphoepithelial lesions. The tumor cells were of CD5-, CD10-, CD20+, BCL2+ and cycline D1- phenotype, and showed a monoclonal rearrangement of immunoglobulin heavy chain genes in the five of six cases examined. Interestingly, Helicobacter pylori (H. pylori) was detected in three (37.5%) of the eight patients, which was significantly lower than previous reports. Two of the H. pylori-positive cases initially underwent H. pylori eradication, but showed no change in their lymphomas after the cure of H. pylori infection. The clinicopathologic findings of the present cases appeared to closely resemble those of colorectal MALT lymphoma with a polypoid appearance and few association of H. pylori infection in their pathogenesis. These gastric polypoid cases may merit separate consideration because of the therapeutic problems they pose.

Adult↗

Breast cancer with choriocarcinomatous features: A case report with cytopathologic details.

A case of breast cancer with choriocarcinomatous features (BCCF) is reported. The patient was a 38-year-old Japanese female with a long history of schizophrenia. Her nursing staff noticed a palpable mass in her right breast, which showed rapid growth. Following cytopathologic confirmation of a malignant breast tumor, she underwent mastectomy with ipsilateral axillary lymph node dissection. Histologic examination revealed BCCF, which was positive for placental alkaline phosphatase and human chorionic gonadotropin (HCG) by immunohistochemistry. The serum HCG level was high. She died 7 months postoperatively, with multiple metastases of BCCF to the chest wall, lung and liver.

Adult↗

Intraoperative hemodynamic predictors of mortality, stroke, and myocardial infarction after coronary artery bypass surgery.

UNLABELLED: Evidence that intraoperative hemodynamic abnormalities influence outcome is limited. The purpose of this study was to determine whether intraoperative hemodynamic abnormalities were associated with mortality, stroke, or perioperative myocardial infarction (PMI) in a large cohort of patients undergoing coronary artery bypass grafting. Risk factors and outcomes were queried from a state-mandated cardiac surgery reporting system at two hospitals in New York, NY. Intraoperative hemodynamic abnormalities were derived from computerized anesthesia records by assessing the duration of exposure to moderate or severe extremes of hemodynamic variables. Multivariate logistic regression identified independent predictors of perioperative mortality, stroke, and PMI. Among 2149 patients, there were 50 mortalities, 51 strokes, and 85 PMIs. In the precardiopulmonary bypass (pre-CPB) period, pulmonary hypertension was a predictor of mortality (odds ratio [OR] 2.1, P = 0.029), and bradycardia and tachycardia were predictors of PMI (OR 2.9, P = 0.007 and OR 2.0, P = 0.028, respectively). During CPB, hypotension was a predictor of mortality (OR 1.3, P = 0.025). Post-CPB, tachycardia was a predictor of mortality (OR 3.1, P = 0.001), diastolic arterial hypertension was a predictor of stroke (OR 5.4, P = 0.012), and pulmonary hypertension was a predictor of PMI (OR 7.0, P < 0.001). Increased pulmonary arterial diastolic pressure post-CPB was a predictor of mortality (OR 1.2, P = 0.004), stroke (OR 3.9, P = 0.002), and PMI (OR 2.2, P = 0.001). Rapid intraoperative variations in blood pressure and heart rate were not independent predictors of these outcomes. These findings demonstrate the prognostic significance of intraoperative hemodynamic abnormalities, including data from pulmonary artery catheterization, to adverse postoperative outcomes. It is not known whether interventions to control these variables would improve outcome. IMPLICATIONS: Intraoperative hemodynamic abnormalities, including pulmonary hypertension, hypotension during cardiopulmonary bypass, and postcardiopulmonary bypass pulmonary diastolic hypertension, were independently associated with mortality, stroke, and perioperative myocardial infarction over and above the effects of other preoperative risk factors.

Blood Pressure↗

The hsp operons are repressed by the hrc37 of the hsp70 operon in Staphylococcus aureus.

The heat-shock proteins are coded for the polycistronic operons hsp70 and hsp60 in Staphylococcus aureus. The hsp70 operon is comprised of five genes, hrc37, hsp20, hsp70, hsp40 and orf35, and the hsp60 is comprised of two genes, hsp10 and hsp60. The hsp70 operon transcribed five different sizes of mRNA from three promoters: P1, the most active promoter, transcribed 6.0 and 3.6 kb mRNAs; P2 transcribed a single 1.8 kb mRNA; and P3 transcribed 4.2 and 2.4 kb mRNAs. The hsp60 operon transcribed a single 2.1 kb transcript from only one promoter, P1. Both operons had a common structure of inverted repeat element (CIRCE, Controlling Inverted Repeat of Chaperon Expression) at the promoter region. All of the transcripts were heat (46 C) inducible. One of the unidentified genes, hrc37, was characterized. The disruptant of the hrc37 in the hsp70 operon enhanced the transcription of both operons at 37 C (derepression). Complementation of the disruptant with the cloned hrc37 plasmid recovered the repression of the transcription of both operons at 37 C. The product of hrc37, Hrc37, was found to bind to the CIRCE element. These findings indicated that Hrc37 from the hsp70 operon repressed the transcription of both the hsp70 and hsp60 operons by binding to the CIRCE element located at the promoter region.

Base Sequence↗

Chromosome-determined zinc-responsible operon czr in Staphylococcus aureus strain 912.

A novel operon, czrAB (zinc-responsible genes), was identified in the chromosome of Staphylococcus aureus. The operon consists of two genes, czrA and czrB. The czrA gene, coding for an 11.5 kDa protein, was homologous to cadC, arsR of S. aureus plasmid pI258 and smtB of Synechococcus PCC7942. The czrB, coding for a 36 kDa membrane spanning protein, was homologous to the czcD gene, cobalt, zinc and the cadmium-resistant factor of Bacillus subtilis and Alcaligenes eutrophus. In the presence of zinc (0.1-10 mM), the transcription of czrAB was enhanced in a concentration-dependent manner. Other heavy metals, such as cobalt, copper, manganese and nickel showed no effect on czrAB expression. The disruptant of the czrB gene became sensitive to zinc ion (MIC, 2 mM; MBC, 10 mM), and the complementation with the plasmid recovered the resistance to zinc at the same concentration as a parental strain (MIC, 5 mM; MBC, 20 mM). The disruptant accumulated intracellular zinc up to 0.4 mg per g dry weight of the organism, while that of the parental strain was 0.25 mg per g dry weight. The findings indicated that the novel operon czrAB should play a role in the transportation of zinc across the cell membrane to maintain the proper intracellular concentration.

Amino Acid Sequence↗

CHOP-Dependent stress-inducible expression of a novel form of carbonic anhydrase VI.

CHOP (also called GADD153) is a stress-inducible nuclear protein that dimerizes with members of the C/EBP family of transcription factors and was initially identified as an inhibitor of C/EBP binding to classic C/EBP target genes. Subsequent experiments suggested a role for CHOP-C/EBP heterodimers in positively regulating gene expression; however, direct evidence that this is the case has so far not been uncovered. Here we describe the identification of a positively regulated direct CHOP-C/EBP target gene, that encoding murine carbonic anhydrase VI (CA-VI). The stress-inducible form of the gene is expressed from an internal promoter and encodes a novel intracellular form of what is normally a secreted protein. Stress-induced expression of CA-VI is both CHOP and C/EBPbeta dependent in that it does not occur in cells deficient in either gene. A CHOP-responsive element was mapped to the inducible CA-VI promoter, and in vitro footprinting revealed binding of CHOP-C/EBP heterodimers to that site. Rescue of CA-VI expression in c/ebpbeta-/- cells by exogenous C/EBPbeta and a shorter, normally inhibitory isoform of the protein known as LIP suggests that the role of the C/EBP partner is limited to targeting the CHOP-containing heterodimer to the response element and points to a preeminent role for CHOP in CA-VI induction during stress.

3T3 Cells↗

Steroidal saponins from the bulbs of Allium karataviense.

Chemical examination of the bulbs of Allium karataviense led to the isolation of five new spirostanol saponins (7-11) and a new furostanol saponin (12), together with a known steroidal sapogenin (1) and five known saponins (2-6). The structures of the new saponins were determined by detailed analysis of their spectral data, including two-dimensional NMR spectroscopy. The steroidal saponins produced by A. karataviense, except for 5 and 6, were found to be based upon (25R)-5 alpha-spirostane-2 alpha,3 beta,5,6 beta-tetrol (alliogenin) and contain a beta-D-glucopyranosyl moiety with the formation of an O-glycoside linkage to C-2 of the polyhydroxylated steroidal skeleton as the common structural feature. The isolated compounds were evaluated for cytostatic activity against human promyelocytic leukemia HL-60 cells.

Allium↗

The results of radiotherapy for T1 glottic cancers; influence of radiation beam energy.

We analyzed the influence of various parameters on the results of radiotherapy for T1 glottic cancer by assessing the outcomes of 60 patients with this cancer who received definitive radiotherapy between 1985 and 1994. Seven patients were treated with a cobalt-60 unit, and the other 53 with a linear accelerator (26 patients at 3-MV, 10 at 6-MV, and 17 at 10-MV). Of the 17 patients treated at 10-MV, 4 also received part of their treatment with a cobalt-60 unit. The total radiation dose ranged from 56 Gy to 70 Gy (mean, 61 Gy). The total radiation dose of 51 patients (85%) was 60 Gy. The factors found to influence local control were the strength of the radiation beam energy and whether or not there was gross tumor invasion of the anterior commissure. The local control rate was 71% in the patients treated with a 10-MV linear accelerator, 56% in those treated with a 6-MV linear accelerator and, 97% in those treated with a cobalt-60 unit or a 3-MV linear accelerator (P = 0.0173). The local control rate was 43% in the patients with gross anterior commissure invasion and 88% in those without (P = 0.0075). We conclude that low energy photon beams are more suitable for the treatment of early glottic cancers, especially if the lesion grossly invades the anterior commissure.

Aged↗

A new experimental system for irradiating tumors in mice using a linear accelerator under specific pathogen-free conditions.

We developed a reliable system for the irradiation of xenografted tumors in mice which allows for accurate local irradiation under specific pathogen-free conditions. The system presented here consists of acrylic supports for mice and an acrylic box connected to a pump through 0.22 microns pore-sized filters. Mice with xenotransplanted tumors growing on their right hind legs were set on the supports and put into the box in a laminar flow hood. The tumors of 7 mice were irradiated simultaneously with X-rays of 6 and 10 MV generated by a linear accelerator at a dose rate of 3.1-4.7 Gy/min. The air was ventilated through filters during irradiation in the closed box. Microorganism tests confirmed that no bacteria entered or left the box. One of the significant characteristics of this setup is that it allows for irradiation under conditions of acute hypoxia, which is obtained using an integrated tourniquet. The dose variation among 7 tumors was less than 1%. The rest of the mouse's body was shielded effectively by a half-field technique and a lead block. As a result, the whole body dose for the mice was 0-4% of the total dose absorbed by the tumor. Due to the high dose rate and the ability to irradiate 7 mice simultaneously under specific pathogen-free conditions, this new system can be considered a time-saving and valuable tool for radiation oncology research.

Animals↗

R&D of long-term life support system by using electrochemically activated biofilm reactor of aquatic animals for space examinations.

We have developed the long-term life support system that enables the experiment of aquatic animals breeding for 90 days or more for the future experiments in orbit. In order to enable long-term breeding of wide aquatic animals, it is necessary to remove nitrate produced by biological nitrification. Then, we examined a denitrification method to use an electrochemical reaction of biofilm-electrode reactor. In this research, we have not kept the aquatic animals actually but imitated breeding of five goldfish. The ammonia of about 250 ppm was added in breeding water through 90 days. As a result, neither ammonia nor nitrite accumulated 0.1 ppm and nitrate could be suppressed to about 10 ppm.

Ammonia↗

Cepharanthin enhances thermosensitivity without a resultant reduction in the thermotolerance of a murine mammary carcinoma.

Cepharanthin (Ce) is a biscoclaurine alkaloid extracted from Stephania cepharantha Hayata. The results of our previous in vitro study indicated that Ce reduces thermotolerance by enhancing thermosensitivity. In the present study, we investigated the in vitro and in vivo effects of Ce on thermosensitivity and thermotolerance using a murine mammary carcinoma, MCa, and C3H/HeN mice. Ce enhanced the thermosensitivity of MCa cells for heating at 44 degrees C not only in vitro but also in vivo. The in vivo enhancement ratio +/- SD of Ce at 100 mg/kg for heating at 44 degrees C was 1.3+/-0.3. The fractionated heat treatments at 44 degrees C for 30 and 60 min with an interval time of 0-6 days resulted in the development of remarkable thermotolerance and the expression of heat shock protein 70 in MCa tumors after the first heating. Ce at 100 mg/kg given immediately after the first heating increased the expression of heat shock protein 70 in MCa tumors, and did not reduce the development of thermotolerance. Ce given immediately before the first or second heating also did not inhibit the thermotolerance. The results of this study suggest that Ce enhances the thermosensitivity of MCa tumors as a thermosensitizer, but that this mild thermosensitizing property of Ce might be insufficient to conquer the remarkable thermotolerance in MCa tumors that develops after the first heating.

Alkaloids↗

[Hepatitis B].

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Diagnosis, Differential↗

[Renal oncocytoma with cystic degeneration: a case report].

A 45-year-old man was referred to our department because of a right renal mass which was incidentally found at a health screening. Ultrasound sonography, computerized tomography and magnetic resonance imaging showed a hypovascular tumor 3 cm in diameter with the fluid at the upper pole of the right kidney, implicating that the tumor was renal cell carcinoma originating from a renal cyst wall, or with central necrosis. A radical nephrectomy was therefore performed. The tumor was dark-brown and contained brown fluid. The histopathological findings showed renal oncocytoma with cystic degeneration.

Adenoma, Oxyphilic↗