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Biomedical subjects

T Yokozawa

Publications and source records attributed to T Yokozawa.

At least 37 records · Page 2Linked to original sources
PubMed2001

Role of ginsenoside-Rd in cisplatin-induced renal injury: special reference to DNA fragmentation.

DNA of LLC-PK(1) cells cultured with cisplatin was fragmented to produce low-molecular-weight structures. Agarose gel electrophoresis of the DNA revealed a ladder pattern characteristic of apoptosis, indicating the induction of apoptosis by cisplatin. However, the degree of apoptosis was lower in cells cultured with cisplatin in the presence of ginsenoside-Rd, and this was accompanied by suppressed leakage of lactic dehydrogenase into the culture medium. The ladder pattern was detected on electrophoresis of DNA in renal tissue samples obtained from rats given an intravenous injection of cisplatin. Such DNA fragmentation was less conspicuous in rats given ginsenoside-Rd orally for 30 days prior to cisplatin administration. Significant suppression of the DNA fragmentation was also demonstrated by densitometry, and measurement of urea nitrogen and creatinine in blood also showed a marked decrease in their respective levels in rats administered ginsenoside-Rd. The present findings suggest that ginsenoside-Rd ameliorates cisplatin-induced renal injury, a process in which apoptosis plays a central role, and thereby causes restoration of the renal function.

Animals↗
PubMed2001

Examination of the nitric oxide production-suppressing component in Tinospora tuberculata.

The component of aqueous Tinospora tuberculata extract that inhibits nitric oxide (NO) production was examined using macrophages activated by the addition of lipopolysaccharide. The aqueous extract was partitioned with ethyl acetate. The aqueous layer was fractionated with a Diaion column. The residue of the aqueous extract was extracted with methanol, and partitioned with ethyl acetate. The ethyl acetate layer was found to be associated with a distinct decrease in the NO level and inducible NO synthase. On further fractionation, the subfraction of E-3 showed high anti-NO activity. N-trans-Feruloyltyramine isolated from E-3 was identified as exhibiting strong anti-NO activity. This compound is the most active component of Tinospora tuberculata with respect to the suppression of NO production.

Animals↗
PubMed2001

Effects of buckwheat in a renal ischemia-reperfusion model.

Experiments were done to find whether buckwheat extract ameliorates the renal injury induced by ischemia-reperfusion. In ischemic-reperfused control rats, the activities of antioxidative enzymes in renal tissue and blood and renal parameters deviated from the normal range, indicating dysfunction of the kidneys. In contrast, when buckwheat extract was given orally for 20 consecutive days before ischemia and reperfusion, the activities of the antioxidation enzymes superoxide dismutase, catalase, and glutathione peroxidase were higher, while thiobarbituric acid-reactive substance levels in serum and renal tissue were lower in the treated rats than in the controls. Decreased levels of urea nitrogen and creatinine in serum demonstrated a protective effect against the renal dysfunction caused by ischemia and recirculation. On the other hand, it was demonstrated that buckwheat extract had a protective effect on cultured proximal tubule cells subjected to hypoxia-reoxygenation, probably by preventing oxygen free radicals from attacking the cell membranes.

Animals↗
PubMed2001

[Extremely high level of serum thyroglobulin after surgery in a patient with follicular thyroid carcinoma. Recurrence, distant metastasis, or other etiology?].

A 67-year-old female patient with a tumor of the thyroid underwent right lobectomy of the thyroid. The tumor was histologically diagnosed as a follicular carcinoma of the thyroid. Serum studies revealed very high (> 8,000 ng/ml) levels of thyroglobulin after surgery. We suspected distant metastases from follicular carcinoma or recurrence in the left lobe of the thyroid. She therefore underwent left lobectomy of the thyroid. No recurrence of follicular carcinoma was recognized in the resected thyroid tissue, but severe autoimmune thyroiditis was diagnosed histologically. Total-body 131I scintigraphy did not show abnormal distant uptake. Serum studies revealed very low levels of thyroglobulin (< 2.0 ng/ml) after the second surgery. We speculate that silent thyroiditis might have occurred after the first surgery, resulting in the high levels of serum thyroglobulin. Silent thyroiditis should be considered as a possible cause of high serum thyroglobulin levels.

Adenocarcinoma, Follicular↗
PubMed2000

Selective hydrogenation of benzophenones to benzhydrols. Asymmetric synthesis of unsymmetrical diarylmethanols

[reaction: see text] trans-RuCl2[P(C6H4-4-CH3)3]2(NH2CH2CH2NH2) acts as a highly effective precatalyst for the hydrogenation of a variety of benzophenone derivatives to benzhydrols that proceeds smoothly at 8 atm and 23-35 degrees C in 2-propanol containing t-C4H9OK with a substrate/catalyst ratio of 2000-20000. Use of a BINAP/chiral diamine Ru complex effects asymmetric hydrogenation of various ortho-substituted benzophenones and benzoylferrocene to chiral diarylmethanols with consistently high ee.

Journal Article↗
PubMed2000

Inhibition of nitric oxide release by an aqueous extract of Tinospora tuberculata.

An aqueous extract of Tinospora tuberculata stems was found to scavenge nitric oxide (NO) in vitro in both cell and cell-free systems. When the aqueous extract was added to lipopolysaccharide-stimulated murine macrophages, it inhibited NO release dose-dependently, and similar activity was found in a cell-free system using sodium nitroprusside as a NO donor. These findings may help to explain, in part, certain pharmacological activities of Tinospora tuberculata.

Animals↗
PubMed2000

Inhibitory effects of an aqueous extract of Apocynum venetum leaves and its constituents on Cu(2+)-induced oxidative modification of low density lipoprotein.

An aqueous extract of Apocynum venetum leaves and its constituents inhibited thiobarbituric acid reactive substances (TBARS) and conjugated-diene formation in the Cu(2+)-induced oxidation of low density lipoprotein (LDL) in vitro. The TBARS formation was most strongly inhibited by chlorogenic acid with an IC(50) value of 1.9 microM, but other constituents were in a range of 2.3-23.3 microM. On the other hand, the lag time in the conjugated-diene formation was dose-dependently prolonged by addition of the aqueous extract. Catechin prolonged the lag time more than 300 min and other constituents such as chlorogenic acid, epicatechin, epigallocatechin, hyperoside and isoquercitrin led to no conjugated-diene formation within 700 min under the experimental conditions.

Cholesterol, LDL↗
PubMed2000

Unilateral surgery supported by germline RET oncogene mutation analysis in patients with sporadic medullary thyroid carcinoma.

Compared to hereditary medullary thyroid carcinoma (MTC), sporadic MTC tends to be unicentric and confined to one lobe. Patients with sporadic MTC usually undergo total thyroidectomy because of a possible hereditary or bilateral process. We evaluated the usefulness of germline RET oncogene mutation analysis in surgery for apparently sporadic MTC and performed unilateral surgery on patients without detectable mutation. In 36 patients with a preoperative diagnosis of apparently sporadic MTC, we performed germline RET oncogene mutation analyses: before surgery in 8 recent patients and after surgery in 28 who had been treated before 1996. Of the latter, 5 had bilateral MTC. DNA samples were extracted from their peripheral blood, and the polymerase chain reaction products of the RET proto-oncogene were analyzed using single-strand conformation polymorphism analysis and the direct sequencing methods. Before 1996 we often performed total thyroidectomy but changed to hemithyroidectomy thereafter, except in one patient with associated Graves' ophthalmopathy. Our minimal standard practice included systematic central and ipsilateral neck dissection. The outcome was assessed in terms of gastrin- and calcium-stimulated plasma calcitonin levels. Germline RET mutations were found in six patients. Five of these patients had bilateral MTC, whereas all 30 patients without mutation had unilateral disease. Hemithyroidectomy in seven of our recent patients resulted in normalization of plasma calcitonin levels in all, although four were found to have microscopic lymph node involvement. In conclusion, hemithyroidectomy with systematic central and ipsilateral neck dissection is an appropriate procedure for patients with sporadic MTC without detectable germline RET mutations.

Adult↗
PubMed2000

Gelatin beads as platforms for targeting molecule and anti-Fas antibody: two major properties of cytotoxic T lymphocytes.

OBJECTIVE: Cytotoxic T lymphocytes (CTL) initially recognize target cells using the T-cell receptor (TCR), then strongly adhere to these cells by accessory molecules, and finally induce apoptosis by Fas ligand (FasL)/Fas or lyse by the granzyme/perforin system. We describe the development of gelatin beads carrying anti-tumor monoclonal antibody (mAb) and anti-Fas mAb mimicking the TCR and FasL, respectively. We hypothesized that these antibody-coated beads can be therapeutically utilized for the elimination of tumor cells. MATERIALS AND METHODS: We evaluated the cytotoxic activity of gelatin beads bearing CH11 (anti-Fas mAb) after incubation with several human leukemia cell lines. Cytotoxic activities were measured using colorimetric DNA fragmentation assay and lactate dehydrogenase (LDH) release assay. RESULTS: We demonstrated that the cytotoxic effects of anti-Fas mAb were markedly enhanced by fixation on gelatin beads. Microscopic examination showed that the beads attached to the target cells and induced their apoptosis. These effects were enhanced further by adding tumor-specific mAb. These in vitro properties of the beads were well reconstituted in the peritoneal cavity of mice. CONCLUSION: Although antibody-coated gelatin beads lack several important properties of natural CTL, such as differentiation, proliferation, and the functions of adhesion molecules, they mimic well the targeting and cytotoxic functions of natural CTL. Our findings suggest that antibody-carrying gelatin beads may be the first step toward the development of artificial CTL and can be applied, for example, to artificial dendritic and stroma cells for the development of novel biotherapeutic approaches.

Animals↗
PubMed2000

Effects of aqueous extracts of Apocynum venetum leaves on spontaneously hypertensive, renal hypertensive and NaCl-fed-hypertensive rats.

Effects of aqueous extracts of Apocynum venetum leaves (Luobuma extracts) on the blood pressure were evaluated in hypertensive animal models, such as spontaneously hypertensive rats (SHR), renal hypertensive rats and NaCl-induced hypertensive rats. In SHR, administration of Luobuma (heat-processed and unprocessed leaves) extracts at a dose of 70 mg/rat per day significantly decreased the systolic blood pressure value, but their decreasing effects were weaker than that of captopril. The urine volume, and the urinary Na(+), K(+) and protein excretions were not significantly different between Luobuma-treated and untreated groups. In 3/4 nephrectomized rats, the Luobuma extracts significantly decreased the systolic blood pressure value, accompanied by significant increases of the urine volume and the urinary Na(+) and K(+) excretions. Furthermore, they decreased the blood urea nitrogen (BUN) level. In NaCl-induced hypertensive rats, the Luobuma extract decreased the systolic blood pressure value. However, it did not change the urinary excretions of Na(+), K(+) and protein. The BUN level was lower than that of control rats, but the serum total cholesterol (TC) level did not changed. From these findings, the Luobuma extracts have an anti-hypertensive effect, possibly due to amelioration of the kidney functions in the three experimental animal models.

Animals↗
PubMed2000

The mechanism of nitric oxide and/or superoxide cytotoxicity in endothelial cells.

We examined the mechanism of nitric oxide (NO) and/or superoxide (O2-)-induced cytotoxicity and the importance of thiols in endothelial cells by treating the cells with superoxide dismutase (SOD), catalase (CAT) and hemoglobin (Hb). Pyrogallol, a O2 generator and precursor of hydrogen peroxide (H2O2), had potent cytotoxic effects on the endothelial cells, but this effect was completely abolished by SOD/CAT. Hb, a NO scavenger, protected the endothelial cells from sodium nitroprusside-induced cytotoxicity. The cytotoxic effect of 3-morpholinosydnonimine (SIN-1), which is thought to form peroxynitrite (ONOO-) as a simultaneous O2- and NO generator, was completely blocked by SOD/CAT or Hb. On the other hand, pretreatment of endothelial cells with diethylmaleate, a glutathione depleter, aggravated the cytotoxicity induced by SIN-1, which was prevented by addition of exogenous glutathione and/or SOD/CAT. These data suggest that the cytotoxicity induced by NO, O2- and ONOO- can be blocked by glutathione, and that this is an important cellular protective mechanism against these reactive oxygen species.

Animals↗
PubMed2000

Protection of the kidney by Wen-Pi-Tang against ischemia-reperfusion injury.

Electrophoretic and densitometric data revealed induction of apoptosis in the kidney due to experimentally induced ischemia-reperfusion injury. Such apoptosis in the kidney was reduced in rats given 62.5 or 125 mg/kg body wt./day Wen-Pi-Tang orally for 30 days prior to ischemia-reperfusion. An increase in the dose of Wen-Pi-Tang was associated with suppressed fragmentation of DNA, a ladder pattern of low-molecular-weight molecules, resulting in a beneficial effect on renal function.

Acute Kidney Injury↗
PubMed2000

Role of Salviae Miltiorrhizae Radix extract and its compounds in enhancing nitric oxide expression.

Excessive production of nitric oxide (NO) and its peroxidant product, peroxynitrite, has been implicated in the pathology of acute and chronic renal failure, and inhibitors of NO production have been shown to exert protective and ameliorative effects against renal epithelial cell damage mediated by enhanced generation of NO. Salviae Miltiorrhizae Radix has exhibited a beneficial effect in the improvement of renal failure. In order to clarify the mechanism responsible, we investigated whether Salviae Miltiorrhizae Radix extract and several of its related compounds, including caffeic acid and its polymers which were isolated by our research group, can regulate the generation and release of NO. The results demonstrated that Salviae Miltiorrhizae Radix extract and these compounds suppressed NO effectively in the systems employing activated macrophages and the arginine-hydrogen peroxide, and that, furthermore, the activity shown by the compounds was higher than that shown by the extract. In addition, direct scavenging of NO was also observed. The present findings suggest that Salviae Miltiorrhizae Radix extract and its compounds are potent NO inhibitors, and that their inhibitory effect on the generation and release of NO may contribute to the previously reported pharmacological effect of Salviae Miltiorrhizae Radix in improving renal function.

Animals↗
PubMed2000

Protective effects of Glycyrrhizae radix extract and its compounds in a renal hypoxia (ischemia)-reoxygenation (reperfusion) model.

Glycyrrhizae radix water extract (GRWE) and its two major constituents glycyrrhizin and 3-glycyrrhetinic monodesmoside, significantly suppressed LDH leakage and MDA release, whereas glycyrrhetinic acid had no effect. On the other hand, in rats subjected to ischemia-reperfusion, the activities of endogenous antioxidant enzymes including catalase and glutathione peroxidase showed recovery, whereas the levels of urea nitrogen and creatinine in serum were reduced by administration of glycyrrhizin orally for 30 days prior to ischemia-reperfusion. These results indicate that GRWE and its two constituents may be promising for amelioration of hypoxia (ischemia)-reoxygenation (reperfusion) injury and improvement of renal function by acting directly or indirectly as antioxidant and oxygen radical-scavenging agents.

Animals↗
PubMed2000

Direct scavenging of nitric oxide by traditional crude drugs.

Thirty-one traditional crude drugs and several pure compounds were examined for their possible regulatory effect on nitric oxide (NO) levels using sodium nitroprusside as a NO donor in vitro. Most of the crude drugs tested demonstrated direct scavenging of NO. Eight crude drugs, including Sanguisorbae Radix, Caryophylli Flos, Gambir, Coptidis Rhizoma, Granati Cortex, Gallae Rhois, Rhei Rhizoma and Cinnamomi Cortex exhibited significant activity (IC50 values < 1000 micrograms/ml), and with the exception of Coptidis Rhizoma, all were found to contain tannins as their major constituents. In addition, some crude drugs containing flavonoids or essential oils also appeared to act against NO. Ten major tannins contained in Sanguisorbae Radix and Rhei Rhizoma showed high scavenging activity (IC50 values < 326.3 micrograms/ml), and 6 of 8 alkaloids obtained from Coptidis Rhizoma also effectively scavenged the NO radical (IC50 values < 455.4 micrograms/ml). It was indicated that these compounds may be the active principles of the crude drugs responsible for NO scavenging. The present results suggest that traditional crude drugs might be potent and novel therapeutic agents for scavenging of NO and the regulation of pathological conditions caused by excessive NO and its oxidation product, peroxynitrite. These findings may also help to explain, at least in part, certain pharmacological activities of crude drugs, especially anti-infection and anti-inflammatory activities.

Free Radical Scavengers↗
PubMed2000

Antioxidative activity of green tea treated with radical initiator 2, 2'-azobis(2-amidinopropane) dihydrochloride.

This study investigated the antioxidative activity of green tea extract, and a green tea tannin mixture and its components, under conditions of radical generation using the hydrophilic azo compound, 2,2'-azobis(2-amidinopropane) dihydrochloride (AAPH) to generate peroxyl radicals at a constant and measurable rate in the cultured renal epithelial cell line, LLC-PK(1), which is susceptible to oxidative damage. Treatment with AAPH decreased cell viability and increased the formation of thiobarbituric acid-reactive substances. However, green tea extract, and the tannin mixture and its components, comprising (-)-epigallocatechin 3-O-gallate (EGCg), (-)-gallocatechin 3-O-gallate (GCg), (-)-epicatechin 3-O-gallate (ECg), (-)-epigallocatechin (EGC), (+)-gallocatechin (GC), (-)-epicatechin (EC), and (+)-catechin (C), showed protective activity against AAPH-induced cellular damage. The tannin mixture and its components exhibited higher antioxidative activity than the green tea extract. Furthermore, EGCg and GCg had higher activity than EGC and GC, respectively. In particular, EGCg exerted the most significant cellular protective activity against AAPH. These results indicate that green tea tannin may inhibit cellular loss and lipid peroxidation resulting from the peroxyl radical generated by AAPH, and that the chemical structure of tannin is also involved in the activity, suggesting that the O-dihydroxy structure in the B ring and the galloyl groups are important determinants for radical scavenging and antioxidative potential.

Amidines↗
PubMed2000

Comparative evaluation of antioxidant potential of alaternin (2-hydroxyemodin) and emodin.

The antioxidant activities of alaternin (2-hydroxyemodin) and emodin were compared for their respective potentials to inhibit lipid peroxidation in the linoleic acid system by the thiocyanate method, to inhibit total reactive oxygen species generation in kidney homogenates using 2',7'-dichlorodihydrofluorescein diacetate, to inhibit peroxynitrite formation by the 3-morpholinosydnonimine system, which generates superoxide radical and nitrogen monooxide, and to scavenge authentic peroxynitrites. Both alaternin and emodin were found to inhibit the peroxidation of linoleic acid by the thiocyanate method in a dose-dependent manner. Whereas the former shows inhibitory activities in reactive oxygen- and nitogen-mediated reactions, the latter does not. These results indicate that alaternin is a potentially effective and versatile antioxidant and can be used to protect biological systems and functions against various oxidative stresses.

Antioxidants↗