Search PubMed⌕ Search

Biomedical subjects

M Kuroda

Publications and source records attributed to M Kuroda.

At least 253 records · Page 14Linked to original sources

Steroidal saponins from the underground parts of Hosta longipes and their inhibitory activity on tumor promoter-induced phospholipid metabolism.

Phytochemical study on the underground parts of Hosta longipes gave six new steroidal saponins together with a known one. The structures of the new compounds were determined by detailed analysis of their 1H- and 13C-NMR spectra including two-dimensional NMR spectroscopy, acid-catalyzed hydrolysis followed by chemical correlation, and by comparison with spectral data of known compounds. The isolated saponins and their aglycones were examined for inhibitory activity on 12-O-tetradecanoylphorbol-13-acetate (TPA)-stimulated 32P-incorporation into phospholipids of HeLa cells to identify new antitumor-promoter compounds.

Anticarcinogenic Agents↗

A novel 16,23-epoxy-5 beta-cholestane glycoside with potent inhibitory activity on proliferation of human peripheral blood lymphocytes from Ornithogalum saundersiae bulbs.

A novel 16,23-epoxy-5 beta-cholestane triglycoside (1) was isolated from the bulbs of Ornithogalum saundersiae (Liliaceae). The structure was determined by extensive spectroscopic analysis. The conformation of the E-ring part of 1 was studied through molecular mechanics and molecular dynamics calculation methods. Compound 1 potently inhibited proliferation of peripheral blood lymphocytes provided from a chronic renal failure patient without causing any cytotoxicity in the lymphocytes and HL-60 human leukemia cells.

Carbohydrate Conformation↗

Primary biliary cirrhosis (PBC)-CREST (calcinosis, Raynaud's phenomenon, esophageal dysfunction, sclerodactyly and telangiectasia) overlap syndrome complicated by Sjögren's syndrome and arthritis.

A 36-year-old woman with primary biliary cirrhosis (PBC)-CREST (calcinosis, Raynaud's phenomenon, esophageal dysfunction, sclerodactyly and telangiectasia) overlap syndrome complicated by Sjögren's syndrome and arthritis is reported. She had suffered from Raynaud's phenomenon, sclerodactyly, morning stiffness, arthralgia and sicca symptoms since 34 years of age. She exhibited an increased level of alkaline phosphatase and hyperglobulinemia at 2.8 g/dl without any symptoms, and histological findings from the biopsy specimen of the liver were consistent with those of PBC. Her human leukocyte antigen (HLA) typing was DR8 homozygous.

Adult↗

Evidence for an increased intracellular free calcium concentration in platelets of bronchial asthma patients.

The pathogenesis of bronchial asthma is not yet fully understood. Recently much attention has been given to the hypothesis that intracellular free calcium ([Ca2+]i) metabolism is abnormal in various diseases. In this study we investigated whether [Ca2+]i exists abnormally in subjects with bronchial asthma. The [Ca2+]i in 32 treated or untreated subjects with bronchial asthma were compared with 63 normal subjects. Resting levels of [Ca2+]i were estimated by loading the fluorescent indicator Fura-2 in washed platelets. The [Ca2+]i level in the control subjects was 129.7 +/- 18.0 nM (mean +/- SD). However, in that of the bronchial asthma patients was 152.7 +/- 44.1 nM, significantly higher than that of the control subjects (p < 0.05). It is well recognized that an increase of [Ca2+]i in vascular smooth muscle involves contraction. The findings suggest that the same phenomenon is quite possible in the tracheal smooth muscle and that it plays an important role in the pathogenesis of bronchial asthma.

Adult↗

Ca2+ increase and pH decrease induced by hypochlorous acid in single quiescent myocytes isolated from rat ventricles.

Cytosolic free calcium concentration ([Ca2+]i) and intracellular pH (pHi) were simultaneously measured with a fluorescence technique using fura-2 and BCECF. Hypochlorous acid (HOC1) increased [Ca2+]i and decreased pHi of single quiescent myocytes isolated from rat ventricles. The HOC1-induced changes in [Ca2+]i and pHi (delta [Ca2+]i and delta pHi) were 129 +/- 18nM and 0.18 +/- 0.02 (mean +/- SD), respectively, with 200 microM HOC1. A positive linear correlation was obtained between delta [Ca2+]i and delta pHi under various extracellular Ca2+, pH, and Na+ conditions. Chelation of extracellular Ca2+ depressed only one-fourth of delta [Ca2+]i, and Ca2+ antagonists (verapamil and nifedipine) did not reduce delta [Ca2+]i, indicating that delta [Ca2+]i originates mainly from intracellular Ca2+ stores. A disulfide-reducing reagent, 1,4-dithiothreitol (DTT), recovered the increased [Ca2+]i and decreased pHi to the control levels. The simultaneous changes in [Ca2+]i and pHi induced by HOC1 and the simultaneous restoration of the normal [Ca2+]i and pHi in cardiac myocytes.

Animals↗

[Multicentricity and concomitant tumors in renal cell carcinoma: analysis by serial section of resected kidneys].

Nephron-sparing surgery was initially limited to the patients with localized renal cancer (RCC) present bilaterally or in a solitary kidney. Recently there is controversy in the indication for partial nephrectomy or enucleation to incidentally defined small RCC with normal opposite kidney. We examined the incidence of multicentricity in 43 kidneys removed for RCC with a diameter of less than 80 mm. The mean diameter of the predominant tumors was 45 mm (range 12 to 80 mm). The kidneys were serially sectioned at 5 mm intervals. Three of 43 kidneys (7%) had multiple RCC. The size of the concomitant tumors ranged from 2 to 15 mm. The multicentricity had no relation to pathological grade, stage, vascular invasion or infiltration pattern. In addition, the other 4 kidneys had 2 adenomas, 1 angiomyolipoma and 1 fibroma. Therefore we observed a 16% incidence of small renal nodules and a 7% multicentricity of RCC in the nephrectomized kidneys with normal opposite kidney.

Adenoma↗

Chimeric TLS/FUS-CHOP gene expression and the heterogeneity of its junction in human myxoid and round cell liposarcoma.

Myxoid liposarcomas have a unique and specific t(12;16)q13;p11) chromosomal translocation. The breakpoint has recently been identified and shown to involve the TLS/FUS gene on chromosome 16 and the CHOP gene on chromosome 12. This translocation causes fusion of these genes resulting in the expression of a novel chimeric TLS/FUS-CHOP message. Using the polymerase chain reaction with primer sets derived from sequences of TLS/FUS and CHOP cDNAs, we could amplify three types of the fusion transcripts from seven of seven samples of myxoid and round cell liposarcomas. In six of the seven positive samples, two kinds of chimeric messenger RNAs were found that have been reported previously. However, the last sample had a novel chimeric message that had an extra sequence of 33 bp derived from the TLS/FUS gene. Thus, it was shown that these fusion transcripts had a varying extent of the sequence of TLS/FUS gene incorporated at the site of the fusion. However, the TLS/FUS-CHOP fusion transcripts were not detected in two pleomorphic liposarcomas or in three myxoid variants of malignant fibrous histiocytomas. Our findings indicate that in liposarcomas TLS/FUS-CHOP fusion transcripts have variations at the junction of chimeric messages, which was the case for Ewing's sarcoma. Detection of the chimeric message by reverse transcription polymerase chain reaction was also suggested to be a useful approach for the diagnosis of myxoid and round cell liposarcomas that have (12;16) translocation, and for distinguishing them from pleomorphic liposarcoma and myxoid variant of malignant fibrous histiocytomas.

Adult↗

Preoperative endocrine therapy in patients with locally advanced prostate cancer.

Recently, there has been increased interest in the application of preoperative endocrine therapy prior to radical prostatectomy for locally advanced cancer in order to enhance surgical curability and increase survival. Between 1986 and 1993, 40 patients with prostate cancer were given endocrine therapy before radical prostatectomy. Fifteen patients had stage B2 disease and 25 stage C. The median duration of preoperative endocrine therapy was 3.8 months, and all the patients subsequently underwent radical prostatectomy, pelvic lymphadenectomy and castration. There was an average 25.5% (0-71.8%) decreases in the maximal cross-sectional area of the prostate gland as determined by transrectal ultrasonography. Twenty-four of 25 patients with elevated levels of serum prostate-specific antigen (PSA) showed normal values after preoperative endocrine therapy. Evaluation of treatment-related histological effects, divided into three grades, revealed that 17 patients had pronounced, 11 moderate and 12 poor or no regression. Thirteen of the 40 patients (33%) demonstrated pathological downstaging of disease status from the diagnosis made at the initial clinical examination. After a median follow-up period of 36 months (3-100 months), 36 of the 40 patients are disease-free; two died of cancer 43 and 50 months after surgery, respectively. These results suggest that preoperative endocrine therapy may play an important role in the management of locally advanced prostatic cancer.

Adenocarcinoma↗

Effect of iron as a new type of phosphate binder in hemodialysis patients.

Hyperphosphatemia is one of the major problems requiring management in the majority of hemodialysis patients and they require phosphate-binding agents to control the hyperphosphatemia. Aluminum hydroxide and calcium compounds are used currently as phosphate-binding agents to treat hyperphosphatemia, but these compounds can cause undesirable side effects. Therefore, the development of new phosphate-binding agents is imperative. It is well known that oral and intravenous administration of iron causes hypophosphatemia. We hypothesized that this side effect of iron may be beneficial for the treatment of hyperphosphatemia in hemodialysis patients. Consequently, we conducted a fundamental and clinical investigation of the effects of iron administration. Membrane permeability of phosphorus in a mixture of sodium ferrous citrate and dessicated aluminium hydroxide in the presence of hydrogenated lecithin as a phosporic compound was examined. Fifteen patients undergoing hemodialysis were treated with 150 mg of sodium ferrous citrate given orally for eight weeks. The permeability of the filtering membrane to phosphorus decreased in accordance with the dosage of sodium ferrous citrate and dessicated aluminum hydroxide. The degree of phosphate-binding effect of sodium ferrous citrate was larger than that of dessicated aluminum hydroxide. Serum phosphorus decreased significantly during the experiment. These results suggest that the oral administration of sodium ferrous citrate as a new phosphate binder is a useful therapeutic method for hemodialysis in patients with hyperphosphatemia.

Administration, Oral↗

Inhibition of parathyroid hormone-related protein release by extracellular calcium in dispersed cells from human parathyroid hyperplasia secondary to chronic renal failure and adenoma.

The relationship between parathyroid hormone-related protein (PTHrP) release from parathyroid cells and extracellular calcium ion concentration was investigated in three cases of parathyroid hyperplasia secondary to chronic renal failure and in four cases of parathyroid adenoma. Amounts of PTHrP released from individual parathyroid cells dispersed from surgical specimens were estimated by cell immunoblot assay. Parathyroid cells from both hyperplasias and adenomas showed significant suppression in the release of PTHrP with increase in extracellular calcium ions, but the amounts of PTHrP released from adenoma cells were significantly larger than from hyperplasia cells. The maximal value for PTHrP released within 120 minutes from adenoma cells was 2.91 +/- 2.11 x 10(-2) fmol/cell ([Ca2+], 0.4 mmol/L), and the minimal value was 1.32 +/- 0.35 x 10(-2) fmol/cell ([Ca2+], 2.0 mmol/L). On the other hand, the maximal value for PTHrP released from hyperplasia cells was 1.79 +/- 1.56 x 10(-2) fmol/cell ([Ca2+], 0.4 mmol/L), and the minimal value was 0.32 +/- 0.19 x 10(-2) fmol/cell ([Ca2+], 2.0 mmol/L). These results demonstrate actual release of PTHrP from abnormal parathyroid tissues into the extracellular space with the response to extracellular calcium ions depending on the cell status. Given the lack of definite histological criteria to differentiate between hyperplasias and adenomas in the parathyroid gland, the presently demonstrated significant difference in the ability to release PTHrP is important in pointing to parathyroid hyperplasia secondary to chronic renal failure as a distinct pathological entity separate from parathyroid adenoma.

Adenoma↗

[Prognostic factors in bladder cancer].

Prognostic factors in bladder cancer are used to determine the prognosis of patients and select the method of treatment. Clinical stage, the number of tumors, size of the main tumor, mode of proliferation, cell type, histological grade, histological stage, mode of spread, and intramural lymphatic and venous invasion are well-known prognostic factors. They are closely related to survival or the disease-free interval. Most prognostic factors are histopathological findings. Now, study of new prognostic factors in bladder cancer related to molecular biological or immunohistochemical technique is ongoing.

Disease-Free Survival↗

Effect of ethanol on DNA synthesis and c-met induction in Chang liver cells with long-term culture.

This investigation was performed to determine whether ethanol affects induction on Chang liver cells of the c-met protooncogene product (c-met), a cell-surface receptor for hepatocyte growth factor (HGF). These cells were cultured for 4 weeks with 5, 50, or 100 mmol/L ethanol, or 10, 100, or 200 mumol/L acetaldehyde. Ethanol was found to inhibit [3H]thymidine incorporation by cells in a dose-dependent manner. In addition, acetaldehyde at 100 mumol/L also inhibited [3H]thymidine uptake. Treatment with recombinant HGF led to enhanced [3H]thymidine incorporation by cells treated with ethanol or acetaldehyde as well as by those left untreated, with no significant differences in the rates of increase among these three cell groups. The amount of c-met messenger RNA, however, was unaffected by treatment with ethanol or acetaldehyde. Expression of c-met as measured by cell ELISA was also unchanged by both treatments. These results suggest that ethanol has no effect on c-met induction on Chang liver cells and that HGF may not be involved in the ethanol induced inhibition of DNA synthesis.

Cells, Cultured↗

Conformation of the C-terminus of endothelin-1 in aqueous solution studied by Monte-Carlo simulation.

The conformation of the C-terminus of endothelin-1 in an aqueous solution has been analyzed by a Monte-Carlo simulation including the hydration energy term. The C-terminus may adopt multiple or flexible conformations in the solution, but the classification of the conformations shows that a comparably large number of conformers take a similar folding form in which the C-terminal chain is extended along the alpha-helix of the N-terminal core, and hydrophobic clusters are formed between the side groups of the C- and N-terminus. The aromatic ring of Trp21 is located at a certain distance from the two charged side groups of Asp8 and Glu10, and the functional groups of the key residues in the N-terminus are uncovered with the C-terminus tail.

Amino Acid Sequence↗

Conformational change of skeletal muscle alpha-actinin induced by salt.

We examined the effect of KCl concentration on conformation of skeletal muscle alpha-actinin. One-dimensional peptide maps of alpha-actinin digested with chymotrypsin indicated that alpha-actinin can take on at least three different conformations depending on the KCl concentration of the solvent, i.e., at low (0-0.02 M KCl), intermediate (0.05-0.2 M KCl), and high (0.3-0.6 M KCl) salt concentration. Viscosity measurement and gel-filtration chromatography of alpha-actinin at these three salt ranges indicated that the axial ratio of alpha-actinin increased as the ionic strength of the solvent decreased. By assuming 45% hydration of the alpha-actinin molecule and using a molecular weight of 210,000, dimensions of alpha-actinin were calculated from viscosity data. The size estimated under the low-salt conditions was 3.2 x 74.2 nm. They were 3.4 x 51.3 nm and 4.5 x 40.1 nm, respectively, in the intermediate and high salt ranges. The result of the gel-filtration chromatography showed that the conformational change was reversible and that the change took place through the elongation and/or shortening of the rod domain of the molecule. We explain the salt-induced length change of alpha-actinin by the twisted-coiling model proposed by McGough and Josephs for erythrocyte spectrin (McGough, A. and Josephs, R. (1990) Proc. Natl. Acad. Sci. USA 87, 5208-5212). Pelleting experiments indicated that the conformational change affected the binding ratio between alpha-actinin and actin.

Actinin↗

Adjuvant and neoadjuvant chemotherapy for invasive bladder cancer.

A total of 20 patients with primary invasive bladder cancer who underwent radical cystectomy received postoperative adjuvant chemotherapy using a CAP (cyclophosphamide, doxorubicin, and cisplatin) or modified M-VAC (methotrexate, vinblastine, pirarubicin, and cisplatin) regimen. In all, 16 of the patients were treated with CAP and 4 received the modified M-VAC regimen. Of the 20 patients, 17 had transitional-cell carcinoma with or without non-transitional-cell elements. All of the patients had tumors with a histological grade of G2 (6 cases) or G3 (14 cases). As for lymph-node metastasis, there were ten N0 cases, three N1 cases, six N2 cases, and one N3 case. Adjuvant chemotherapy was usually commenced 2 weeks after the surgery and was given every 3-4 weeks for two or three cycles. The 5-year survival rate of these 20 patients was 65.9%, whereas that of 49 patients who did not receive any adjuvant chemotherapy was 30.2%. Regarding toxicity, both of the adjuvant chemotherapy regimens used in this study were generally well tolerated. The most common toxic effects were gastrointestinal symptoms, alopecia, and myelosuppression. Another 19 patients with invasive transitional-cell carcinoma of the bladder received 2 or 3 cycles of neoadjuvant chemotherapy using the modified M-VAC or MEC (methotrexate, epirubicin, and cisplatin) regimen. Of 18 pathologically evaluable patients who underwent radical cystectomy or partial cystectomy, the stage was pT0 in 3 cases (17%), pTis in 3 (17%), pT1 in 3 (17%), and pT2 or higher in 9 (50%). The 4-year survival rate of 18 patients who received neoadjuvant chemotherapy was 71.5%. Regarding toxicity, one patient died of a bowel complication after surgery, and the complication was suggested to be drug-induced.

Adenocarcinoma↗

A case of neural cell adhesion molecule-positive peripheral T-cell lymphoma associated with human T-cell lymphotrophic virus type 1 showing an unusual involvement of the gastrointestinal tract during the course of the disease.

We report a case of neural cell adhesion molecule (NCAM)-positive peripheral T-cell lymphoma (PTCL), pleomorphic, medium and large cell type according to the updated Kiel classification, which was associated with human T-cell lymphotrophic virus type 1 (HTLV-1). The patient showed an unusual involvement of the gastrointestinal tract forming a bulky mass during the course of his disease, and a relatively indolent clinical course for 53 months until death. Phenotypic analysis showed CD2+, CD3-, CD4+, CD5+, CD7+, CD8-, CD16-, CD56+, and CD57- phenotype. Human T-cell lymphotrophic virus type 1 antibody was detected by the enzyme-linked immunosorbent assay. The proviral integration of HTLV-1 and the monoclonal rearrangements of T-cell receptor beta and gamma genes also were confirmed in DNA extract from fresh material. This fact calls attention to NCAM as one of the potential factors playing a role in the localization and behavior of lymphomas even within the category of PTCL associated with HTLV-1, ie, adult T-cell leukemia/lymphoma (ATLL).

Antigens, Surface↗