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Biomedical subjects

Y Jin

Publications and source records attributed to Y Jin.

At least 361 records · Page 20Linked to original sources

In vivo microdialysis study of a specific inhibitor of soluble guanylyl cyclase on the glutamate receptor/nitric oxide/cyclic GMP pathway.

1. Nitric oxide (NO) is known to stimulate soluble guanylyl cyclase, thereby eliciting an elevation of guanosine 3':5'-cyclic monophosphate (cyclic GMP) in target cells. Recently, a selective inhibitor of soluble guanylyl cyclase, 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ), has been identified and characterized in vitro. We have investigated the in vivo effects of ODQ on the glutamate receptor/NO/ cyclic GMP pathway by monitoring extracellular cyclic GMP during microdialysis of the cerebellum or the hippocampus of freely-moving adult rats. 2. Intracerebellar administration of ODQ (1-100 microM) via the microdialysis probe inhibited, in a concentration-dependent manner, the basal extracellular level of cyclic GMP. The maximal inhibition, measured after a 20 min perfusion with 100 microM ODQ, amounted to 80% and persisted unchanged as long as ODQ was perfused. When ODQ was removed from the perfusion stream after 20 min, the levels of cyclic GMP started to recover, suggesting reversibility of guanylyl cyclase inhibition by ODQ. 3. The cyclic GMP response evoked in the cerebellum by NMDA (200 microM) or by alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA; 100 microM) was largely attenuated by 100 microM ODQ. The pattern of the inhibition curves suggests competition for guanylyl cyclase between ODQ and the NO generated by NMDA or AMPA receptor activation. 4. ODQ (100 microM) prevented the elevation of extracellular cyclic GMP levels provoked by intracerebellar infusion of the NO generator S-nitroso-N-acetylpenicillamine (SNAP; 1 mM). The inhibition of the SNAP effect was rapidly relieved when ODQ was removed from the perfusion fluid. However, ODQ (100 microM) was unable to affect the cyclic GMP response elicited by 5 mM SNAP, in keeping with the proposed idea that ODQ binds to the "NO receptor' in a reversible and competitive manner. 5. Infusion of ODQ (10, 100 or 300 microM) into the hippocampus of freely-moving rats diminished the basal extracellular level of cyclic GMP. The maximal inhibition amounted to 50% and was produced by 100 microM ODQ. 6. The cyclic GMP response observed when 1 mM SNAP was perfused in the hippocampus, similar in percentage terms to that seen in cerebellum, was dramatically reduced during co-infusion of 100 microM ODQ. 7. ODQ appears to act in vivo as a selective, reversible and possibly competitive inhibitor of the soluble guanylyl cyclase targeted by NO. This enzyme may generate most (about 80%) of the cyclic GMP found under basal conditions in the extracellular space of the cerebellum. In the hippocampus, about 50% of the basal cyclic GMP does not seem to originate from the ODQ-sensitive soluble guanylyl cyclase.

Animals↗

Differential activation of the Ras/extracellular-signal-regulated protein kinase pathway is responsible for the biological consequences induced by the Axl receptor tyrosine kinase.

To understand the mechanism of Axl signaling, we have initiated studies to delineate downstream components in interleukin-3-dependent 32D cells by using a chimeric receptor containing the recombinant epidermal growth factor (EGF) receptor extracellular and transmembrane domains and the Axl kinase domain (EAK [for EGF receptor-Axl kinase]). We have previously shown that upon exogenous EGF stimulation, 32D-EAK cells are capable of proliferation in the absence of interleukin-3. With this system, we determined that EAK-induced cell survival and mitogenesis are dependent upon the Ras/extracellular-signal-regulated protein kinase (ERK) cascade. Although the phosphatidylinositol-3 kinase pathway is activated upon EAK signaling, it appears to be dispensable for the biological actions of the Axl kinase. Furthermore, we demonstrated that different threshold levels of Ras/ERK activation are needed to induce a block to apoptosis or proliferation in 32D cells. Recently, we have identified an Axl ligand, GAS6. Surprisingly, GAS6-stimulated 32D-Axl cells exhibited no blockage to apoptosis or mitogenic response which is correlated with the absence of Ras/ERK activation. Taken together, these data suggest that different extracellular domains dramatically alter the intracellular response of the Axl kinase. Furthermore, our data suggest that the GAS6-Axl interaction does not induce mitogenesis and that its exact role remains to be determined.

Adaptor Proteins, Signal Transducing↗

P50 changes with visual interference in normal subjects: a sensory distraction model for schizophrenia.

Twenty-five normal subjects were tested in a Conditioning-Testing (S1-S2) auditory P50 study. Each subject was tested twice under two experimental conditions: distraction condition (with light interference) and control condition (without interference). Results showed that S1 P50 amplitude was significantly decreased with visual interference compared with that in the control condition, while the S2 response remained unchanged. Consequently, the S2/S1 gating ratio was also increased remarkably in the distraction condition. The auditory EP changes with the visual distraction in normals closely resembled the abnormal findings in schizophrenic subjects. These data may provide an alternative model to elucidate the psychophysiological mechanism that possibly rules the changes of attention in schizophrenia.

Acoustic Stimulation↗

Neutralization of TGF-beta by anti-TGF-beta antibody attenuates kidney hypertrophy and the enhanced extracellular matrix gene expression in STZ-induced diabetic mice.

Diabetic nephropathy is characterized by renal hypertrophy, thickening of basement membranes, and accumulation of extracellular matrix in the glomerular mesangium and the interstitium. Our previous investigations have shown that high glucose concentration increases transforming growth factor (TGF)-beta1 mRNA in mesangial and proximal tubule cells and that treatment with anti-TGF-beta antibody results in prevention of the effects of high glucose on cell growth (e.g., induction of cellular hypertrophy) and the stimulation of collagen biosynthesis. We evaluated in vivo the functional role of the renal TGF-beta system in diabetic kidney disease by treatment of streptozotocin-induced diabetic mice with either a neutralizing monoclonal antibody against TGF-beta1, -beta2, and -beta3 (alphaT) or nonimmune murine IgG for 9 days. Diabetic mice given IgG demonstrated total kidney and glomerular hypertrophy, significantly elevated urinary TGF-beta1 protein, and increased mRNAs encoding TGF-beta1, type II TGF-beta receptor, alpha1(IV) collagen, and fibronectin. Treatment of diabetic mice with alphaT prevented glomerular hypertrophy, reduced the increment in kidney weight by approximately 50%, and significantly attenuated the increase in mRNA levels without having any effect on blood glucose. The antibody was without significant effect on mRNA levels in nondiabetic mice. This is the first demonstration that the early characteristic features of diabetic renal involvement, which include hypertrophy and increased matrix mRNAs, are largely mediated by increased endogenous TGF-beta activity in the kidney and that they can be significantly attenuated by treatment with neutralizing anti-TGF-beta antibodies.

Animals↗

[Bronchial cyst in a patient with a high serum CA19-9 concentration that fluctuated with the cyst fluid volume].

A 44-year-old woman was found to have an abnormally high concentration of CA19-9 in serum. Five years later, she underwent a right upper lobectomy for an abnormal shadow on a chest roentgenogram, because it was thought to indicate a malignant tumor. A chest CT scan revealed a cyst with fluid in the right upper lobe. During the 5 years before the lobectomy, the serum CA19-9 concentration rose when the cyst fluid volume increased, and fell when the cyst fluid volume decreased. Before the operation, the serum CA19-9 concentration was very high and the cyst was swollen. The cyst wall was found to be lined with ciliated columnar epithelial cells and to contain hyaline cartilage and smooth muscle, which led to the diagnosis of bronchial cyst. The surface epithelium and cyst fluid were positively stained by a monoclonal antibody against CA19-9. The serum CA19-9 concentration decreased and was within the normal range 3 months after the operation.

Adult↗

Effect of nucleotides 37 and 38 on cleavage of tRNAPhe precursors.

Splicing is required for tRNA maturation when the precursors contain the introns. In order to determine whether nucleotides 37 and 38 affect splicing, yeast tRNAPhe precursors with different nucleotides 37 and 38 were prepared by in vitro mutagenesis and cleaved by the purified yeast tRNA-splicing endonuclease. The precursors with purine nucleotides at N37 and N38 were found to be the best substrates for the enzyme. When N37 and N38 were replaced by pyrimidine nucleotides, few precursors could be cleaved by the endonuclease. If one is pyrimidine nucleotide, the other one is purine nucleotide at these positions, the cleavage efficiencies are between the two groups of precursors stated above. The pyrimidine nucleotides at these positions might affect the fine structures of the precursors or the distance between the splicing sites, so that the precursors can not be fixed or anchored on the enzyme well, leading to the poor cutting.

Mutagenesis, Site-Directed↗

[Clinical study on painless labor under drugs combined with acupuncture analgesia].

To study the analgesia efficacy of drugs combined with acupuncture analgesia for painless labor, 462 normal pregnancy women were observed. During the latent phase in labor, several analgesia methods: acupuncture analgesia, analgesics, magnetotherapy and auricular acupressure, TENS combined with dihydroetorphine were used respectively. While the intrauterine pressure and the peripheral content of beta-EP were measured during labor, the experiments of SEPS were also performed on healthy adults to demonstrate the analgesia efficacy of those analgesia methods. The combination of drugs with acupuncture is an excellent method for painless labor without any complications and all the mothers and babies are safety. The effectiveness is 97.5%. The results demonstrate that the mechanism of analgesia efficacy should be regulated the incoordinate uterine action and improve the hypertonic status of uterus, but also can decrease the pain threshold and elevate the tolerance of uterine contractions during labor.

Acupressure↗

Effect of vasopressin on delayed neuronal damage in hippocampus following cerebral ischemia and reperfusion in gerbils.

Mongolian gerbils were used as delayed neuronal damage (DND) animal models. At the end of 15 minute cerebral ischemia and at various reperfusion time ranging from 1 to 96 hours, the content of water and arginine vasopressin (AVP) in the CA1 sector of hippocampus were measured by the specific gravity method and radioimmunoassay. Furthermore, we also examined the effect of intracerebroventricular (ICV) injection of AVP, AVP antiserum on calcium, Na+, K(+)-ATPase activity in the CA1 sector after ischemia and 96 hour reperfusion. The results showed that AVP contents of CA1 sector of hippocampus during 6 to 96 hour recirculation, and the water content of CA1 sector during 24 to 96 hour were significantly and continuously increased. After ICV injection of AVP, the water content and calcium in CA1 sector of hippocampus at cerebral ischemia and 96 hour recirculation further increased, and the Na+, K(+)-ATPase activity in CA1 sector was remarkably decreased as compared with that of control. While ICV injection of AVP antiserum, the water content and calcium in CA1 sector were significantly decreased as compared with that of control. These suggested that AVP was involved in the pathophysiologic process of DND in hippocampus following cerebral ischemia and reperfusion. Its mechanism might be through the change of intracellular action mediated by specific AVP receptor to lead to Ca ions over-load of neuron and inhibit the Na+, K(+)-ATPase activity, thereby to exacerbate the DND in hippocampus.

Animals↗

[Clinical applications of China-made saline-filled breast implants--a report of 62 cases].

To evaluate the China-made saline-filled breast implants, we observed 62 patients (123 sides of breasts) who received augmentation mammaplasty from March 1994 to May 1995. The implants of 200 to 450 ml were manufactured in Shanghai. All the implants were placed beneath the pectoralis major muscle and a transient over-inflation was used. Fifty-nine patients had satisfactory results. One case developed breast shrinking postoperatively due to possible damage to the implant. Another two cases were not quite satisfactory because of associated breast ptosis. Thirty-two cases were followed up for 3 months and demonstrated nice-looking and soft breasts. We conclude that (1) the quality of the China-made saline-filled breast implant is good. And (2) transient over-inflation of the implant during the operation is advantageous and is worth recommending.

Adult↗

[Studies on the mutagenicity of artificial musk].

Artificial musk-raw material, using as a substitute for traditional Chinese medicine musk, a new drug of class I was assessed for mutagenicity. The micronucleus rates of polychromatocyte in the bone marrow of mice were 2.8, 1.3 and 1.0/1000 when the treated dosage was 1800, 700 and 350 mg/kg. The results of Ames test for the strains TA97, TA98, TA100 and TA102 were negative with and without S9 mix when the concentration of artificial musk was 625, 1,250, 2,500 and 5,000 micrograms/plate, respectively. The chromosome aberration rates were 1.0, 0.8, 1.2% when the treated dosage was 360, 180, 90 mg/kg, respectively. The above results proved that no mutagenicity was found for artificial musk.

Animals↗

A clinical study on TCM differentiation of symptoms and signs in pregnancy hypertension syndrome.

An epidemiological investigation was made into the diagnostic types of 457 cases of pregnancy classified according to differentiation of symptoms and signs by traditional Chinese medicine (TCM) with the aim of finding out its relationship with pregnancy hypertension syndrome (PHS). The total occurrence rate of PHS was 36.8%. In early pregnancy, 65.9% of patients with deficiency of yin of the liver had a high rate of developing PHS, while in the intermediate stage, 61.6% of patients with deficiency of the spleen and exuberance of the liver were most liable to develop it. In 50 cases diagnosed and treated on the basis of TCM differentiation of symptoms and signs the incidence was reduced to be 20%. The changes of such biochemical indices as ACh, AChE, cholic acid and gastrin in different diagnostic types during pregnancy, as well as the effect of spleen-invigorating therapy on these indices in pregnancy with deficiency of the spleen were also observed.

Adult↗

Defective recycling of synaptic vesicles in synaptotagmin mutants of Caenorhabditis elegans.

Synaptotagmin, an integral membrane protein of the synaptic vesicle, binds calcium and interacts with proteins of the plasma membrane. These observations suggest several possible functions for synaptotagmin in synaptic vesicle dynamics: it could facilitate exocytosis by promoting calcium-dependent fusion, inhibit exocytosis by preventing fusion, or facilitate endocytosis of synaptic vesicles from the plasma membrane by acting as a receptor for the endocytotic proteins of the clathrin AP2 complex. Here we show that synaptic vesicles are depleted at synaptic terminals in synaptotagmin mutants of the nematode Caenorhabditis elegans. This depletion is not caused by a defect in transport or by increased synaptic vesicle release, but rather by a defect in retrieval or synaptic vesicles from the plasma membrane. Thus we propose that, as well as being involved in exocytosis, synaptotagmin functions in vesicular recycling.

Aldicarb↗

A kinase-deficient splice variant of the human JAK3 is expressed in hematopoietic and epithelial cancer cells.

Signal transduction of cytokine receptors is mediated by the JAK family of tyrosine kinases. Recently, the kinase partners for the interleukin (IL)-2 receptor have been identified as JAK1 and JAK3. In this study, we report the identification of splice variants that may modulate JAK3 signaling. Three splice variants were isolated from different mRNA sources: breast (B), spleen (S), and activated monocytes (M). Sequence analysis revealed that the splice variants contain identical NH2-terminal regions but diverge at the COOH termini. Analyses of expression of the JAK3 splice isoforms by reverse transcriptase-polymerase chain reaction on a panel of cell lines show splice preferences in different cell lines: the S-form is more commonly seen in hematopoietic lines, whereas the B- and M-forms are detected in cells both of hematopoietic and epithelial origins. Antibodies raised against peptides to the B-form splice variant confirmed that the 125-kDa JAK3B protein product is found abundantly in hematopoietic as well as epithelial cells, including primary breast cancers. The lack of subdomain XI in the tyrosine kinase core of the B-form JAK3 protein suggests that it is a defective kinase. This is supported by the lack of detected autokinase activity of the B-form JAK3. Intriguingly, both the S and B splice isoforms of JAK3 appear to co-immunoprecipitate with the IL-2 receptor from HUT-78 cell lysates. This and the presence of multiple COOH-terminal splice variants coexpressed in the same cells suggest that the JAK3 splice isoforms are functional in JAK3 signaling and may enrich the complexity of the intracellular responses functional in IL-2 or cytokine signaling.

Amino Acid Sequence↗

Altered DNA recognition and bending by insertions in the alpha 2 tail of the yeast a1/alpha 2 homeodomain heterodimer.

The yeast MAT alpha 2 and MATa1 homeodomain proteins bind cooperatively as a heterodimer to sites upstream of haploid-specific genes, repressing their transcription. In the crystal structure of alpha 2 and a1 bound to DNA, each homeodomain makes independent base-specific contacts with the DNA and the two proteins contact each other through an extended tail region of alpha 2 that tethers the two homeodomains to one another. Because this extended region may be flexible, the ability of the heterodimer to discriminate among DNA sites with altered spacing between alpha 2 and a1 binding sites was examined. Spacing between the half sites was critical for specific DNA binding and transcriptional repression by the complex. However, amino acid insertions in the tail region of alpha 2 suppressed the effect of altering an a1/alpha 2 site by increasing the spacing between the half sites. Insertions in the tail also decreased DNA bending by a1/alpha 2. Thus tethering the two homeodomains contributes to DNA bending by a1/alpha 2, but the precise nature of the resulting bend is not essential for repression.

Base Sequence↗

Vasodilatory actions of calcitonin gene-related peptide and nitric oxide in parenchymal microvessels of the rat hippocampus.

Calcitonin gene-related peptide (CGRP) and nitric oxide (NO) are potent dilators in a variety of vascular beds. Recent evidence suggests that NO may serve as an intermediary messenger for CGRP and/or CGRP may serve as an intermediary messenger for NO in the expression of vasodilation. The present study was designed to provide an initial characterization of the responses to NO and CGRP in parenchymal microvessels and to determine whether NO and/or CGRP act as intermediaries for one another. Microvessels in the parenchyma of in vitro hippocampal slices from rat brain were examined using computer-assisted videomicroscopy. The resting diameter of the microvessels ranged from 9 to 26 microm. Treatment with the nitric oxide synthase inhibitor, N(G)-nitro-L-arginine (L-NNA; 100 microM) constricted vessels to 64.2% +/- 3.0% of resting luminal diameter. Sodium nitroprusside (SNP; 1 microM), a donor of NO, reversed the L-NNA-induced vasoconstriction by 77.0% +/- 15.0%. CGRP alone (10 nM) elicited a small but significant vasodilatory effect on resting vascular tone (2.3% +/- 0.6%). In the presence of L-NNA, CGRP elicited a significant dose-dependent vasodilatory response, and 10 nM CGRP elicited a sizeable response, reversing the L-NNA-induced constriction by 84.3% +/- 15.5%. This CGRP-induced dilation was inhibited by pretreatment with the CGRP receptor antagonist, CGRP fragment (8-37) (1 microM). In contrast, pretreatment with 1 microM CGRP fragment (8-37) did not attenuate the SNP-induced dilation in the presence of L-NNA. Taken together, these findings demonstrate that CGRP and NO are potent dilators of parenchymal microvessels, and that NO provides a substantial relaxant effect on resting tone. In addition, the results indicate that CGRP is not a necessary intermediary in NO-induced dilation, and that NO is not a necessary intermediary in CGRP-induced dilation in parenchymal microvessels.

Animals↗

Chromosomal abnormalities involving 11q13 are associated with poor prognosis in patients with squamous cell carcinoma of the head and neck.

BACKGROUND: In individual patients with squamous cell carcinoma of the head and neck (SCCHN), established prognostic factors do not satisfactorily predict clinical outcome. Although the karyotype is an independent prognostic factor in certain hematologic malignancies and solid tumors, no data have been reported concerning the possible relationship between chromosomal abnormalities and clinical outcome in patients with SCCHN: METHODS: In 116 cases of primary SCCHN, short term cultures were analyzed cytogenetically during 1987 through 1991, the karyotypes were divided into four groups: k1, normal (n = 35); k2, numeric changes only (n = 31); k3, simple structural abnormalities (n = 27); and k4, complex karyotypes (n = 23). The patients were followed for at least 18 months after diagnosis or until death. RESULTS: The 2-year survival rate was lower in the k4 subgroup (35%) than in the k1, k2, and k3 subgroups taken together (61%), both in the series as a whole (P = 0.02), and in the largest tumor site subgroup, laryngeal squamous cell carcinoma (n = 32), (P = 0.04). The most prevalent breakpoint was in chromosome band 11q13, occurring in 11 tumors, 10 of which belonged to the k4-subgroup. The 2-year survival rate was lower for patients with 11q13 rearrangements (20%) than for those without (60%), both in the series as a whole (P = 0.001), and in the k4-subgroup (P = 0.02). CONCLUSIONS: The results suggest that in SCCHN the presence of a complex karyotype is associated with poor prognosis, particularly when 11q13 rearrangements are present.

Adult↗