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Biomedical subjects

D J Yang

Publications and source records attributed to D J Yang.

At least 73 records · Page 4Linked to original sources

[Studies on the sweet principles from the leaves of Cyclocarya paliurus (Batal.) Iljinskaya].

Four intensely sweet compounds (I-IV) were obtained from the leaves of Cyclocarya paliurus (Batal.) Iljinskaya. The structure of compound I was elucidated by chemical and spectroscopic methods as 20,24-epoxy-dammarane-(3 beta,12 beta,24R)-12-O-alpha-L-rhamnopyranosyl-25- hydroxyl-3-O-alpha-(5'-O-acetyl)-L-arabinofuranoside. It is a new natural product, named cyclocarioside A, and is the main sweet principle of this plant, possessing about 200 times the sweetness intensity of sugar.

Drugs, Chinese Herbal↗

Rotator interval tear: a case report.

Rotator cuff tear is one of the most common shoulder disorders. Most of the tears involve the critical area of the supraspinatus tendon. The rotator interval tear is extremely rare. Tear in this area is important due to its relationship with shoulder instability, different clinical symptom and different management. Recently we have uneventually treated a case with rotator interval tear after a violent throwing injury. The purpose of the paper is to emphasize the clinical differences of this unusual tear.

Humans↗

[Reversed phase high performance liquid chromatography of tetracyclines].

The present paper describes a quantitative determination method of tetracyclines by reversed phase high performance liquid chromatography. The method used a Waters 10 C18 4.6 nm ID x 250 nm reversed phase column, with a mobile phase composed of 14% acetonitrile-3% dimethylformamide-83% water containing 0.02 mol/L citric acid (pH-2.5), the detector wavelength was set at 350 nm, and the flow rate was maintained at 1.0 ml/min. Demethylchlortetracycline, epi-demethylchlortetracycline, demethyltetracycline, epi-demethyltetracycline, tetracycline, epi-tetracycline, chlortetracycline and epi-chlortetracycline can be separated highly efficiently. The tetracyclines and their anhydro- products can be separated on the same column with 15% acetonitrile- 15% dimethylformamide- 70% 0.02 mol/L citric acid as the mobile phase, and detected at UV 270 nm.

Chromatography, High Pressure Liquid↗

Characteristics of an infinite life span diploid human fibroblast cell strain and a near-diploid strain arising from a clone of cells expressing a transfected v-myc oncogene.

Diploid human fibroblasts were transfected with a plasmid carrying a v-myc oncogene linked to the neo gene or with a vector control carrying a neo gene. Drug-resistant clones were isolated and subcultured as needed. All populations went into crisis and eventually senesced. But while they were senescing, viable-appearing clones were noted among the progeny of a transfected population that expressed the v-myc oncogene. After several months, these cells began replicating more rapidly. Karyotype analysis indicated that they were clonally derived since all of them had 45 chromosomes, including 2 marker chromosomes. This cell strain was designated MSU-1.1. Similar analysis showed that cells from an earlier passage were diploid. These cells were designated MSU-1.0. Both strains have undergone more than 200 population doublings since their siblings senesced, without any change in chromosome complement. Both strains express the v-myc protein and have the same integration site for the transfected v-myc and neo genes. The MSU-1.0 cells cannot grow without exogenously added growth factors. The MSU-1.1 cells grow moderately well under the same conditions and grow to a higher saturation density than MSU-1.0 cells. Since the chance of human cells acquiring an infinite life span in culture is very rare, the data suggest that MSU-1.1 cells are derived from MSU-1.0 cells. The expression of v-myc is probably required for acquisition of an infinite life span, since this phenotype did not develop in populations not expressing this oncogene. However, expression of v-myc is clearly not sufficient, since all of the progeny of the clone that gave rise to the MSU-1.0 cells expressed this oncogene, but the vast majority of them senesced.

Animals↗

N-(3,5-dichlorophenyl)succinimide nephrotoxicity: evidence against the formation of nephrotoxic glutathione or cysteine conjugates.

The agricultural fungicide N-(3,5-dichlorophenyl)succinimide (NDPS) induces nephrotoxicity via one or more metabolites. Previous studies suggested that glutathione is important for mediating NDPS-induced nephropathy. The purpose of this study was to examine the possibility that a glutathione or cysteine conjugate of NDPS or an NDPS metabolite might be the penultimate or ultimate nephrotoxic species. In one set of experiments, male Fischer 344 rats were administered intraperitoneally (i.p.) NDPS (0.4 or 1.0 mmol/kg) 1 h after pretreatment with the gamma glutamyltranspeptidase inhibitor AT-125 (acivicin) (10 mg/kg, i.p.) and renal function was monitored at 24 and 48 h. In general, AT-125 pretreatment had few effects on NDPS-induced nephropathy. In a second set of experiments, rats were treated i.p. or orally (p.o.) with a putative glutathione (S-(2-(N-(3,5-dichlorophenyl)succinimidyl)glutathione (NDPSG), a cysteine (S-(2-(N-(3,5-dichlorophenyl)succinimidyl)cysteine (NDPSC) (as the methyl ester) or N-acetylcysteine (S-(2-(N-(3,5-dichlorophenyl)succinimidyl)-N-acetylcysteine (NDPSN) conjugate of NDPS (0.2, 0.4 or 1.0 mmol/kg) or vehicle and renal function was monitored at 24 and 48 h. An intramolecular cyclization product of NDPSC, 5-carbomethoxy-2-(N-(3,5-dichlorophenyl)carbamoylmethyl)-1,4-th iazane-3-one (NDCTO) was also examined for nephrotoxic potential. None of the compounds produced toxicologically important changes in renal function or morphology. The in vitro ability of the conjugates to alter organic ion accumulation by cortical slices was also examined. All of the conjugates tested caused a reduction in p-aminohippurate (PAH) accumulation at a conjugate bath concentration of 10(-4) M, but none of the conjugates reduced tetraethylammonium (TEA) uptake. In a third experiment, the ability of the cysteine conjugate beta-lyase inhibitor aminooxyacetic acid (AOAA) (0.5 mmol/kg, i.p.) to alter the nephrotoxicity induced by two NDPS metabolites, N-(3,5-dichlorophenyl)-2-hydroxysuccinimide (NDHS) or N-(3,5-dichlorophenyl)-2-hydroxysuccinamic acid (NDHSA) (0.2 mmol/kg, i.p.), was examined. AOAA pretreatment had no effect on NDHS- or NDHSA-induced nephrotoxicity. These results do not support a role for a glutathione or cysteine conjugate of NDPS or and NDPS metabolite as being the penultimate or ultimate nephrotoxic species.

Aminooxyacetic Acid↗

Synthesis and in vitro receptor binding studies of fluorotamoxifen analogues.

We describe the synthesis of new fluorotamoxifen analogues with the fluorine atom positioned on the end of the aliphatic chain of tamoxifen. The binding of fluorotamoxifens to cytosol estrogen receptors of rat uteri was determined with [3H]estradiol (5 nM). The fluorotamoxifens had similar or superior binding affinities compared with tamoxifen. The IC50 value was as follows: tamoxifen, 5 x 10(-7) M; fluorotamoxifen (VII), 5 x 10(-7) M; N,N-diethylfluorotamoxifen (IV)-cis, 1 x 10(-6) M, and trans, 2 x 10(-7) M; and (cis) fluoromethyl-N,N-diethyltamoxifen (VI) 1 x 10(-7) M. Therefore, the fluorinated tamoxifens have potential use in imaging estrogen receptors by PET.

Animals↗

Malignant transformation of human fibroblasts by a transfected N-ras oncogene.

The only ras oncogene as yet identified in cells from human fibrosarcomas is N-ras, but the relationship between N-ras oncogene expression and the malignant state of these cell lines is not known. To determine if expression of an N-ras oncogene causes human cells to become malignant, we transfected the N-ras oncogene from human leukemia cell line 8402, cloned into a high expression vector pSV N-ras, into MSU-1.1 cells, a nontumorigenic, infinite life span fibroblast cell strain with a normal morphology and a stable near-diploid karyotype. The transformants formed distinct foci composed of morphologically transformed cells. Cells from such foci expressed higher than normal levels of N-ras protein, exhibited growth factor independence, and formed large colonies in soft agar at a high frequency. Injection of progeny of these focus-derived cells s.c. into athymic mice resulted in progressively growing, invasive malignant tumors (round cell, spindle cell, or giant cell sarcomas) which reached a diameter of 6 mm in 3 to 4 weeks. Injection of focus-derived or tumor-derived cells i.v. resulted in tumors in various organs of the mice. The focus-derived cell strain tested, as well as the majority of the cells derived from the tumor it produced, exhibited the same near-diploid karyotype as the parental MSU-1.1 cells. Cells transfected with an N-ras oncogene that was expressed at a normal level formed only a single, indistinct focus, and cells from that focus were not malignant.

Animals↗

Osteoid osteoma: clinical and investigative features.

From 1979 to 1988, 15 cases of osteoid osteoma were diagnosed and treated at our hospital. There were 10 males and 5 females, the average age at the time of diagnosis was 17.2 years (from 5 to 54 years). The clinical features were night pain and localized pain in most cases. There was distinct pain relief by salicylate in 58% of the patients with a therapeutic trial. The duration of symptoms before diagnosis averaged 17.9 months (from 1 month to 10 years). Most of the lesions were located in the lower extremities, predominantly in the femur. The hip was a commonly affected site in children and young adults. The X-ray findings in the affected area were classical of the lesion in only 47% of the cases, therefore, preoperative localization of the nidus was aided by either tomography or CT scan. Intraoperative localization by use of an image intensifier and by taking X-rays of the excised specimen has proven to be reliable. All cases underwent en bloc resection of the lesion, and all of the patients were symptom free immediately after the operation, except for one recurrence. A second operation was performed in this case 2 years later and was successful, with pathological confirmation. Fourteen tumors were confirmed by histopathological study, one case could not be confirmed by pathological examination, however the patient obtained complete relief of symptoms postoperatively.

Adolescent↗

Synthesis and receptor binding studies of (+/-)1-iodo-MK-801.

The glutamate analogue N-methyl-D-aspartate (NMDA) binds to a subset of glutamate receptors that are coupled to a voltage-sensitive cation channel. This NMDA-linked channel is the likely binding locus of the potent anticonvulsant MK-801. To develop single-photon emission computed tomography (SPECT) probes of this brain channel, we synthesized (+/)1-iodo-MK-801 and (+/-)1-[125I]iodo-MK-801. The effect of (+/-)1-iodo-MK-801 on ligand binding to the NMDA-linked glutamate receptor site was assessed using a rat brain homogenate assay. (+/-)1-Iodo-MK-801 displaced the dissociative anesthetic ligand [3H]N-[1-(2-thienyl)cyclohexyl]piperidine ([3H]TCP) binding with an IC50 of 1 microM, which is a 10-fold lower binding affinity than that of (+/-)MK-801. In in vivo autoradiographic studies, (+/-)MK-801 failed to block selective uptake of (+/-)1-iodo-MK-801 in rat brain. These results suggest that (+/-)1-iodo-MK-801 may not be a suitable ligand for mapping NMDA-linked glutamate receptor channels.

Animals↗

[Tinnitus treated with combined traditional Chinese medicine and Western medicine].

Cases of annoying tinnitus were selected for this observation. They were examined by general physical examination, otoscopy and some of them by audiometry and tinnitus masking patterns test, and/or Ecoch G and BSER. Two groups, TCM-WM and controls, were designed with patient's sexes, ages, severity of tinnitus almost evenly distributed. Different kinds of medicines were given to the patients of 2 groups with single blind trial. For the controls, only western medicines such as valium, nicotinic acid, mixture bromides, vitamin B Co, ATP and carbamazepine (if 100 mg of lidocaine added to 50% glucose solution intravenously was effective) were taken orally. For TCM-WM group patients, besides the drugs used above, herbal decoctions were given twice a day, and observed for 5 days per therapeutic course. The medicinal herbs consist of: Rhizoma Gastrodiae, Ramulus Uncariae cum Uncis, Poria cocos, Flos Chrysanthemi, Akebia quinata, Radix Polygoni Multiflori, Fructus Liquidambris, Radix Rehmanniae, Rhizoma Alismatis, Radix Scrophulariae, Fructus Lycii, Radix Glycyrrhizae, Semen Plantaginis and Semen Vaccariae. Of the therapeutic results in 32 cases of TCM-WM group, 11 cases (34.4%) showed absence of tinnitus, 16 (50%) improved, and 5 (15.6%) failed. The total effective rate was 84.4%. In 27 cases of the controls, 5 cases (18.6%) showed absence of tinnitus, 10 (37%) improved, and 12 (44.4%) failed. The total effective rate was 55.6%. It showed that the therapeutic results of TCM-WM group was better than those of the controls (P less than 0.05).

Adult↗

Nephrotoxicity of N-(3,5-dichlorophenyl)succinimide metabolites in vivo and in vitro.

The experimental fungicide N-(3,5-dichlorophenyl)succinimide (NDPS) has been shown to produce selective nephrotoxicity at least in part through the actions of one or more metabolites. The purpose of this study was to (1) determine the nephrotoxic potential of three known NDPS metabolites; N-(3,5-dichlorophenyl)-2-hydroxysuccinimide (NDHS), N-(3,5-dichlorophenyl)-2-hydroxysuccinamic acid (NDHSA), and N-(3,5-dichlorophenyl)malonamic acid (DMA) and (2) examine the role of renal biotransformation in NDPS-induced nephrotoxicity. In one set of experiments, male Fischer 344 rats were administered a single intraperitoneal (ip) injection of NDPS or a NDPS metabolite (0.2, 0.4, or 1.0 mmol/kg) or vehicle (sesame oil, 2.5 ml/kg) and renal function was monitored at 24 and 48 hr. Both NDHS and NDHSA administration (0.2 or 0.4 mmol/kg) resulted in nephrotoxicity similar to that produced by NDPS (0.4 or 1.0 mmol/kg). DMA administration resulted in only minor renal effects. Addition of NDPS to renal cortical slices prepared from naive Fischer 344 rats resulted in decreases in p-aminohippurate (PAH) and tetraethylammonium (TEA) accumulation at NDPS media concentrations of 10(-4) and 10(-5) M or greater, respectively. Pretreatment of rats with microsomal enzyme activity modifiers (phenobarbital, 3-methylcholanthrene, cobalt chloride, or piperonyl butoxide) had little effect on in vitro effects of NDPS on PAH or TEA accumulation. A pattern of PAH or TEA uptake similar to that observed for NDPS was observed in vitro with NDPS-d4, a nonnephrotoxic analog of NDPS labeled on the succinimide ring with deuterium. Of the NDPS metabolites tested in vitro for nephrotoxicity, only NDHS produced decreases in PAH and TEA accumulation similar to those produced by NDPS. These results suggest that the NDPS metabolites NDHS and NDHSA are nephrotoxic compounds. However, the role of these metabolites in NDPS-induced nephrotoxicity remains to be determined. In addition, it appears that NDPS has direct effects on renal function, but these effects do not appear to be of major toxicological significance in vivo. Direct renal bioactivation of NDPS or its known metabolites to nephrotoxic species does not appear to occur in vitro.

Animals↗

NMDA receptor channels: labeling of MK-801 with iodine-125 and fluorine-18.

Methods for labeling the glutamate channel blocking agent MK-801 with iodine-125 (125I) and fluorine-18 (18F) are described. Radioiodine was incorporated in the 1- or 3-positions of the aromatic ring of (+/-)MK-801 by solid-state halogen exchange techniques. Attachment of the [18F]fluoromethyl group to the bridgehead methyl position was achieved by reaction of [18F]fluoride with the triflamide alcohol 8 or the novel cyclic sulfamate 9 recently reported by Merck chemists. Radiochemical yields of (+/-) 13-[18F]-fluoromethyl-MK-801 were greater than 72%, EOB; radiochemical purity greater than 99%. In competitive binding studies using rat brain homogenates, (+/-)3-bromo-MK-801 showed greater affinity than (+/-)MK-801 for the glutamate-linked channel. The experimental log P (2.1 +/- 0.1) of MK-801 is optimal for transit of the blood-brain barrier. These preliminary findings support further testing of 3-[123 I]iodo-MK-801 and (+/-)13-[18F]fluoromethyl-MK-801 as possible agents for in vivo mapping of the glutamate receptor complex.

Animals↗

The HuT series of 'carcinogen-transformed' human fibroblast cell lines are derived from the human fibrosarcoma cell line 8387.

In 1977 Kakunaga reported the carcinogen-induced transformation of the diploid human fibroblast cell line KD into focus-forming, morphologically altered cells. Cell lines were developed from 15 individual foci. These exhibited an infinite lifespan in culture and all those that were tested (7/7) formed malignant tumors (sarcomas) in athymic mice. The existing cell lines, designated HuT-11 to HuT-14, have been studied intensively during the past decade as examples of human fibroblasts malignantly transformed by treatment with a chemical carcinogen, 4-nitroquinoline-1-oxide. Recently, in comparing the HuT-11, HuT-12 and HuT-14 cell lines with KD cells, McCormick and Maher (Mutat. Res., 199, 273-291, 1988) found evidence that the malignant cells could not have been derived from the latter. But, this did not rule out the possibility that as the target cells for his original study of carcinogen-induced transformation, Kakunaga had inadvertently used cells from some other, unidentified normal individual. Since the donor of such cells would not be known and the original cell line was not available, it would be impossible to determine the degree of identity between such a target cell line and the HuT cell lines. However, in the course of examining methods for such testing, we recently became aware that the isozyme pattern of these HuT cell lines was identical to that of the human fibrosarcoma-derived cell line 8387 established in 1966. We here report that the HuT cell lines and the 8387 cell line also exhibit an identical series of HLA determinants and identical restriction fragment length polymorphisms (RFLPs). Assuming that each of these three assays measures independently inherited characteristics, the chance that an unrelated donor of the fibroblasts that gave rise to the HuT cell lines happened to possess characteristics identical to those of the patient whose fibrosarcoma gave rise to the 8387 cell line is 1 x 10(-8). Therefore, we conclude that 8387 cells are the source of the malignant cells designated HuT from Kakunaga's original transformation experiment. Additional RFLP analysis, using a probe made from M13 bacteriophage DNA which detects a hyperpolymorphic 'minisatellite' pattern in human DNA, also showed that DNA from HuT-14 cells and from 8387 cells exhibit identical banding patterns, indicating that the cell lines were taken from the same individual. The latter banding patterns differed from that observed with DNA from KD cells.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Structure-nephrotoxicity relationships for meta-substituted N-phenylsuccinimides.

The N-phenylsuccinimides are being evaluated as experimental agricultural fungicides. The purpose of this study was to examine the relationship between the electron withdrawing or electron donating properties of phenyl ring substituents on meta-substituted N-phenylsuccinimide (NPS) derivatives and the nephrotoxic potential of the corresponding fungicides. Male Fischer 344 rats were administered a single intraperitoneal injection of a succinimide (0.4 or 1.0 mmol/kg) or vehicle (sesame oil, 2.5 ml/kg), and renal function monitored at 24 and 48 hr. Non-halogen-substituted NPS derivatives produced little evidence of nephrotoxicity at the doses used in this study. Among the meta-halogen derivatives of NPS, N-(3-chlorophenyl)succinimide (NCPS) was the most nephrotoxic. NCPS-induced nephrotoxicity was characterized by diuresis, proteinuria, hematuria, elevated blood urea nitrogen (BUN) concentration, decreased organic ion accumulation and proximal tubular necrosis. However, all renal effects produced by NCPS were mild to moderate. These results suggest that the electron withdrawing or donating property of a functional group is not a good predictor of the nephrotoxic potential for the corresponding fungicide. In addition, lipophilicity did not correlate with nephrotoxic potential for the meta-substituted NPS derivatives evaluated in this study.

Animals↗

Effect of microsomal enzyme activity modulation on N-(3,5-dichlorophenyl)succinimide-induced nephrotoxicity.

N-(3,5-Dichlorophenyl)succinimide (NDPS) is an experimental agricultural fungicide which has been shown to be a selective nephrotoxin. The purpose of this study was to determine if a NDPS metabolite contributes to acute NDPS-induced nephrotoxicity. Male Sprague-Dawley or Fischer 344 rats were pretreated with a microsomal enzyme inducer [phenobarbital (PB) or 3-methylcholanthrene (3-MC)] or inhibitor [cobalt chloride (CoCl2) or piperonyl butoxide (PIBX)] followed by a single intraperitoneal injection of NDPS (0.2, 0.4 or 1.0 mmol/kg) or vehicle (sesame oil, 2.5 ml/kg). Renal function was monitored at 24 and 48 h. CoCl2 or PIBX pretreatment reduced NDPS-induced diuresis, proteinuria and hematuria, and reduced the increases seen in the blood urea nitrogen (BUN) concentration and kidney weight. NDPS-induced decreases in organic ion accumulation were not markedly altered by CoCl2 or PIBX pretreatment. PB pretreatment enhanced all NDPS- (0.2 mmol/kg) induced renal effects, while 3-MC pretreatment protected against NDPS-induced diuresis, proteinuria, hematuria, and increases in the BUN concentration observed in both rat strains. Kidney weight and organic ion uptake changes were not substantially different between NDPS-treated rats with or without 3-MC pretreatment. It was concluded that a metabolite(s) contributes to or is responsible for acute NDPS-induced nephrotoxicity and that at least 1 toxic metabolite might be of extrarenal origin.

Animals↗