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Biomedical subjects

Y Jin

Publications and source records attributed to Y Jin.

At least 505 records · Page 28Linked to original sources

[Comparative experimental study of nerve repairs by classical suture or biological adhesive].

The respective possibilities of nerve reparation with classical microsutures or biological glue (bioglue) were compared on experimental rat sciatic nerve lesions. Seventy rats were operated upon, and 69 results can be interpreted. 22 had a microsuture, 47 anastomosis with bioglue (Tissucol). The animals were followed for 120 days, and the results assessed on muscular testing, electrostimulation, optic microscopic histology, and morphometry. Five anastomosis dysjunctions occurred in the bioglue group, because of technical errors. All other animals improved from the 60th day. From the histological view point, the results with bioglue were more satisfactory, because of the absence of foreign body reaction to sutures; the authors conclude that because of the equivalent results on nerve function, and better histological results with bioglue, its use is preferable to repair nerves, especially when microsuture is technically difficult.

Animals↗

The relationship between bone morphogenetic protein and neoplastic bone diseases.

The monoclonal antibody against bovine bone morphogenetic protein was used for demonstration of bone morphogenetic protein (BMP) in neoplastic bone diseases. The avidin-biotin-peroxidase complex method demonstrated that BMP mainly exists in the cytoplasm of tumor cells of osteosarcoma and chondrosarcoma. Immunostaining showed that a majority of osteosarcomas and all of the chondrosarcoma cells contained a large quantity of BMP. Conversely, none of the fibrosarcomas showed positive staining. Thus, it was possible to differentiate osteosarcomas from fibrosarcomas by immunostaining. In fibrous dysplasia of bone, BMP was abundant in the fibrocellular tissue that had osteogenic activity. In contrast, fibrous tissue of ossifying fibroma showed weak positive staining; only the osteoblasts rimming the bone showed a positive reaction. Immunostaining showed that BMP was also detected in other neoplastic bone diseases such as osteoma, chondroma, and other tumors.

Antibodies, Monoclonal↗

[Studies on the pharmacokinetics of BMY-28100 (I)].

The pharmacokinetics of BMY-28100 have been studied in rats and monkeys upon oral administration of 14C-BMY-28100. 1. In rats administered with BMY-28100 at a single oral dose of 20 mg/kg, the peak blood level of the drug was 6.30 micrograms equiv./ml at 1 hour after administration. Blood levels declined biphasically, thereafter. The AUC value was 37.0 micrograms equiv..hr/ml, and was 97% of that observed after intravenous administration. This suggests that BMY-28100 is absorbed at a high absorption rate from the gastro-intestinal tract. 2. In monkeys administered with a single oral dose of 20 mg/kg, the peak blood level was 4.26 micrograms equiv./ml at 3 hours after administration. Thereafter, blood levels declined biphasically as did in rats. The AUC was 38.9 micrograms equiv..hr/ml, which is similar to that observed in rats. 3. Urinary and fecal excretion after 20 mg/kg oral administration were 60.9% and 38.1%, respectively, in rats, and 40.3% and 51.2%, respectively, in monkeys. 4. Although absorption from gastro-intestinal tract was delayed by food intake, this did not affect the total amount absorbed in rats. 5. The absorption rates were similar in rats administered with 20 and 60 mg/kg, while a lower rate was obtained with 200 mg/kg. 6. In rats, biliary excretion was 28.5% of dose administered. Thirty-nine percent of the biliary radioactivity was reabsorbed from the intestinal tract. 7. No differences between sexes were observed in absorption and excretion in rats administered with the drug at 20 mg/kg orally. 8. In rats administered with 20 mg/kg, the radioactivity distributed rapidly to the whole body. High levels of radioactivity were found in gastro-intestinal tract, kidney, urinary bladder, aorta and liver. The radioactivity was removed rapidly from the tissues. Autoradiograms of the whole body were consistent with the measured tissue distribution. Relatively high levels of radioactivity were found in aorta, fascia, and ligament at 0.5, 1, 6, and 24 hours. 9. In vivo protein binding, which increased with time after administration, was 56.8 to 73.5% in rat and 36.3 to 58.6% in monkey. The in vitro protein binding at 0.4 to 50 micrograms/ml of drug concentration was 50.0 to 54.7% in rat, 32.3 to 35.0% in monkey, and 33.4 to 36.3% in human. 10. A stability test of 14C-BMY-28100 in plasma solution showed that the drug decomposed gradually into relatively polar compound(s). At 8 and 24 hours, the proportions of unchanged 14C-BMY-28100 were 53.2% and 5.9%, respectively.

Administration, Oral↗

[Studies on the pharmacokinetics of BMY-28100 (II)].

Studies were done in rats on placental transfer and excretion into milk of 14C-BMY-28100 upon single oral administration. Studies on absorption, distribution and excretion of 14C-BMY-28100 were also done upon multiple dosing. 1. Fetal tissue concentration of the drug reached a maximum at 6 hours after dosing on day 18 of gestation. The highest concentration observed was only 0.56 microgram equiv./g in fetal kidney; The transfer of radioactivity into the fetus was low. Similar results were obtained from whole body autoradiograms performed in rats on day 12 and day 18 of gestation. 2. Concentrations of radioactivity in milk reached a maximum of 0.60 microgram equiv./ml at 1 hour after administration, and gradually decreased thereafter. The maximum concentration in milk was 10% of the plasma concentration measured at the same time. 3. In the multiple oral administration study, 24 hours blood levels of radioactivity rose progressively with each dose, and reached a level 3.8 times higher than that observed with single dosing by the final (21st) administration. Tissue concentrations were relatively high in aorta, kidney and large intestine as were found upon single administration. However, the ratios of these levels between multiple and single dosing were lower than those observed in blood; 1.7, 3.6 and 2.9 for aorta, kidney and large intestine, respectively. Urinary and fecal excretion were constant after the 2nd administration.

Administration, Oral↗

Immunohistochemical observations on bone morphogenetic protein in normal and abnormal conditions.

Localization of bone morphogenetic protein (BMP) in human tissues and cells is important for investigating the mechanism of bone induction. A stable cell line secreting monoclonal antibody against bovine BMP (bBMP-McAb) was obtained by the hybridoma technique. The result of immunohistochemical staining (ABC method) showed that BMP is distributed along collagen fibers of normal bone, in periosteal cells, and in mesenchymal cells of marrow stroma. Little BMP can be found in bone cells of lamellar bone or in calcified bone matrix. BMP may be abundant in human tooth anlagen such as predentin, cells of the outer and inner enamel epithelium, and cells of dental sac generating bone. BMP is found in the cytoplasm of tumor cells of osteosarcoma and chondrosarcoma. Immunohistochemical staining showed that BMP plays a role in bone fracture healing. The ability of BMP-McAb to detect BMP and to inhibit the generation of new bone also makes it potentially useful in diagnosing, treating, and providing a prognosis for osteosarcoma and other bone diseases.

Animals↗

Desferrithiocin and desferrioxamine B. Cellular pharmacology and storage iron mobilization.

3H-Desferrithiocin (DFT) has been synthesized from desmethyl desferrithiocin. The uptake and release of this 3H siderophore and of its iron complex have been studied in cultured rat hepatocytes and systematically compared to 14C desferrioxamine B (DFO). At 37 degrees, the uptake of both chelators is strictly proportional to the extracellular concentration and no toxicity is observed up to, at least, 1 mM. Uptake of 3H DFT is rapid and reaches a plateau after ca. 1 hr. The accumulation of 3H DFT attains a maximum three times that of 14C DFO and the plateau is reached much more rapidly. Upon reincubation in a drug-free medium of cells that had accumulated 3H DFT, most of the 3H label is rapidly released in the culture medium. These kinetic parameters suggest that the accumulation of these two chelators results from their diffusion across cellular membranes, as a function of the gradient of concentration between the cellular compartment and the extracellular medium. Differential centrifugation of homogenates from hepatocytes incubated with 3H DFT shows that the bulk of cell associated 3H-label (82%) is found in the cytosol, whereas a small proportion (14.5%) is present in the particulate fraction. Isopycnic centrifugation on sucrose gradients suggests that 3H-label associated with the particulate fraction is localized within mitochondria. In contrast, 14C DFO distributes in almost equal proportions between cytosol and the particulate fraction (MLP). At least part of the 14C-label in MLP is associated with lysosomes. Rat hepatocytes cultivated for long term in synthetic culture medium have been used to study iron mobilization by chelators from 59Fe loaded cells. DFT mobilizes iron more rapidly than DFO. This effect is also observed in vitro with ferritin, where, in addition, DFT is much more efficient than DFO to mobilize iron at acidic pH. These results strongly suggest that different iron mobilization from cultured hepatocytes results from differences in the cellular pharmacology of these two chelators and, in particular, in their rate of uptake, cellular accumulation levels and subcellular localizations. DFT could mobilize iron from cytosol and, possibly, to a small extent from mitochondria, whereas DFO would do so from cytosol and lysosomes.

Animals↗

Inhibition of eukaryotic translation by nucleoside 5'-monophosphate analogues of mRNA 5'-cap: changes in N7 substituent affect analogue activity.

Nucleotide cap analogues of 7-methylguanosine 5'-monophosphate (m7GMP) were synthesized in which the 7-methyl moiety was replaced with 7-ethyl (e7), 7-propyl (p7), 7-isopropyl (ip7), 7-butyl (b7), 7-isobutyl (ib7), 7-cyclopentyl (cp7), 7-(carboxymethyl) (cm7), 7-benzyl (bn7), 7-(2-phenylethyl) [7-(2-PhEt)], and 7-(1-phenylethyl) [7-(1-PhEt)]. These derivatives were assayed as competitive inhibitors of capped mRNA translation in reticulocyte lysate. We observed that N7 alkyl and alicyclic substituents larger than ethyl significantly decreased the inhibitory activity of these cap analogues presumably by decreasing their affinity for cap binding proteins, which participate in the initiation of translation. This result defined a maximum size for this class of N7 substituents in the nucleotide binding domain of cap binding proteins. Like m7GMP, the N7-substituted GMP derivatives synthesized in this study were found to be predominantly in the anti conformation as determined by proton NMR analyses. However, bn7GMP and 7-(2-PhEt)GMP, which have aromatic N7 substituents, were more effective than m7GMP as competitive inhibitors of translation. The increased affinity of bn7GMP for cap binding proteins was further examined by synthesis of beta-globin mRNA containing 5'-bn7G, 5'-m7G, or 5'-e7G cap structures. These modified mRNAs were tested as translation templates. Messenger RNA capped with bn7G was observed to increase the translation activity of the template 1.8-fold relative to that of its m7G-capped mRNA counterpart. By contrast, e7G-capped mRNA was 25% less active than m7G-capped mRNA.2+V photo-cross-linking of m7G-capped mRNA to cap binding proteins

Animals↗

EEG alpha photic driving abnormalities in chronic schizophrenia.

Periodic photic stimuli across the entire electroencephalographic (EEG) frequency range were used in an attempt to assess EEG functional differences between chronic schizophrenic patients and control subjects. The EEG responses to these photic stimuli were significantly attenuated in the schizophrenic patients, specifically at the frequencies within the EEG alpha range. The schizophrenic patients also showed an alpha range attenuation in the "no stimulus" EEG alpha measure, such that there was a significant correlation across subjects between the "stimulus" and "no stimulus" EEG alpha range abnormalities. These abnormalities are discussed with reference to possible dysfunctional thalamic mechanisms involved in the pacing of EEG alpha activity and the gating of information through the cerebral cortex.

Adult↗

Inhibition of adenylate cyclase in bovine ciliary process and rabbit iris ciliary body to alpha 2-adrenergic agonists.

Alpha 2-adrenergic inhibition of adenylate cyclase in bovine ciliary processes and rabbit iris ciliary body (ICB) was studied. With bovine ciliary process membrane, it was found that cAMP production in the presence of 1 microM isoproterenol was increased with increasing NaCl concentrations from 0 to 200 mM. Clonidine, an alpha 2-adrenergic agonist, produced a NaCl concentration-dependent inhibition of cAMP production in the presence of isoproterenol with a maximum inhibition at 200 mM NaCl (P less than 0.05). NaCl concentrations had no effect on basal adenylate cyclase activities and activity in the presence of clonidine alone. The alpha 2-adrenergic agonists, lofexidine, clonidine and p-amino-clonidine were tested for their ability to inhibit isoproterenol-stimulated adenylate cyclase in bovine ciliary process membrane in the presence of 200 mM NaCl. Their dose-response curves showed that they had similar IC50's but the maximum inhibition differed among these agonists. Clonidine was found to be a partial agonists producing 55% of the inhibition obtained with lofexidine. The specificity of inhibition of isoproterenol-stimulated adenylate cyclase by alpha 2-agonists and blockade by pertussis toxin was examined by adenine labelling in rabbit ICB. The results demonstrate that alpha 2-adrenergic receptors exert specific inhibitory effects on adenylate cyclase activity in rabbit ICB, which are mediated by an inhibition guanine nucleotide regulatory protein, Gi.

Adenine↗

Genetic convergence during serial in vitro passage of a polyclonal squamous cell carcinoma.

A cell line was established from an in situ squamous cell carcinoma of the skin (Bowen's disease), and its in vitro karyotypic evolution was cytogenetically analyzed. Initially, considerable genetic heterogeneity was evident. Nine cytogenetically abnormal clones, eight of which were apparently unrelated, were found among the 83 metaphases analyzed from the primary culture and the first passage. With increasing time in culture this complexity was reduced, so that a single clone dominated passages 7-11. The clone that emerged from this genetic convergence had a t(12;17)(p13;q21) as the sole abnormality. Our findings indicate that the cytogenetic multiclonality that has been repeatedly detected in short-term cultures of squamous cell carcinomas is not caused by the in vitro conditions. Instead, the principles of Darwinian selection apply: the altered, but stable, selection pressure facing a newly established and initially multiclonal cell line will lead to a reduction of genetic heterogeneity until the one clone that now has the proliferative advantage outgrows the other subpopulations.

Biological Evolution↗

Trisomy 7 and sex chromosome loss in human brain tissue.

Short-term cultures of nonneoplastic brain tissue from 11 patients, seven of whom had a malignant brain tumor, were cytogenetically examined. In only a single case was a wholly normal chromosome complement detected; the remaining ten cases exhibited mosaicism with clonal numerical aberrations found alongside cells carrying a normal karyotype. The abnormal clones were characterized by trisomy 7, the loss of the Y chromosome in men and an X chromosome in women, or by combinations thereof. No structural aberrations were present. Our findings demonstrate that although -Y, -X, and +7 have in the past repeatedly been associated with brain tumors, these changes presumably reflect normal in vivo organ mosaicism and, thus, should not be accepted as neoplasia-specific in this context.

Adult↗

[Studies on water extract limits of Caulis Aristolochiae Manshuriensis].

This paper reports the result of the content determination of water extract of Caulis Aristolochiae Manshuriensis. It has been found that the yellower colour of section, the richer the contents of the water extract, and the contents tend to decrease when stored for a long time or unsuitably kept. The contents of water extract have nothing to do with the diameter or the producing area. We suggest using cold extraction to determine the contents of water extract of Caulis Aristolochiae Manshuriensis and the content should not be less than 16 percent.

Cold Temperature↗

[Experimental study of composites of bovine bone morphogenetic protein and bio-active glass ceramic implanted into surgically produced periodontal bony defects in dogs].

Bovine bone morphogenetic protein (bBMP) was incorporated with bio-active glass ceramic (BGC). The composite of bBMP-BGC and BGC were implanted into the surgically produced periodontal osseous defects in dogs. Observations at 10, 16, 20, and 24 weeks show that the implants of BMP-BGC have the ability of bone induction and enhance the regeneration of periodontal bony defects in a relatively short time, but the implants of BGC alone only have the ability of bone-conduction, these is no bone-induction ability, and made a more long time in repairing the periodontal bony defects.

Animals↗