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Biomedical subjects

Y Gu

Publications and source records attributed to Y Gu.

At least 325 records · Page 18Linked to original sources

[A study on relation between effect of HB vaccination and time of the second injection].

Three kinds of hepatitis B vaccination schedule in neonates were compared. The schedule included 0, 40 day, 6 month; 0, 50 day, 6 month; 0, 60 day, 6 month; and was controlled by the 0, 30 day, 6 month schedule. The results showed that there was no statistically significant difference among three kinds of schedule, no matter who were neonates of HBs Ag-positive mother or neonates of HBsAg-negative mother. These indicated that in areas with poor condition, such as mountain, island, the second injection of hepatitis B vaccine in neonates may be completed within 30-60 days.

Hepatitis B↗

Modulation of glycine affinity for NMDA receptors by extracellular Ca2+ in trigeminal neurons.

Glycine and the divalent cation Ca2+ play key roles in regulating the activity of excitatory amino acid NMDA receptor channels. There is accumulating evidence that the concentration of glycine at the synaptic cleft is below a saturated level. We examined the effect of external Ca2+ on NMDA responses in various concentrations of glycine in isolated trigeminal neurons. We found that external Ca2+ potentiated NMDA responses and this potentiation occurred only when glycine sites were unsaturated. Since single-channel conductance decreases in the high external Ca2+ solution, the observation cannot be explained by an increase in Ca2+ influx through the channels. Studying the dose-response curves for glycine in different Ca2+ solutions, we found that the apparent dissociation constant (EC50) for glycine decreases with increasing external Ca2+ concentrations. Kinetics studies of glycine binding to NMDA receptors indicated that external Ca2+ causes a decrease in the off rate of the glycine binding, while having no effect on the on rate. Our analyses suggest that the apparent glycine affinity increases by about 3.7 times in Ca-containing solution. Thus, external Ca2+ contributes to the unusually high glycine affinity for NMDA receptors and may have a role in regulating the NMDA receptor channel activities during intensive or sustained neuronal stimulation.

Animals↗

Inhibition of CDK2 activity in vivo by an associated 20K regulatory subunit.

The major events of the cell division cycle are triggered by periodic changes in the activity of cyclin-dependent protein kinases (CDKs). In mammals, the members of the CDK family include CDK2 and CDC2, which are thought to be involved in the control of DNA replication and mitosis, respectively. The protein kinase activity of these enzymes is controlled by a complex array of mechanisms. Activation of the CDK catalytic subunit requires association with a positive regulatory subunit (cyclin) and phosphorylation (at Thr 160 in CDK2). This activated complex can be inhibited by additional phosphorylation at Thr 14 and Tyr 15. Here we report the identification of a new mechanism for the regulation of CDK2 activity. We find that CDK2/cyclin complexes in mouse fibroblasts associate tightly with a 20K protein (CAP20). Complexes containing CAP20 were isolated from cell lysates and found to have negligible kinase activity, indicating that CAP20 association in vivo may inhibit CDK2 activity. We purified CAP20 from 3T3 cells and found that low concentrations of the protein completely inhibit the kinase activity of CDK2 in vitro. Thus CAP20 represents a new negative regulatory subunit that inhibits the activity of CDK2/cyclin complexes in mammalian cells.

3T3 Cells↗

Cloning of the ALL-1 fusion partner, the AF-6 gene, involved in acute myeloid leukemias with the t(6;11) chromosome translocation.

Reciprocal chromosome translocations involving 11q23 are frequently associated with acute leukemias, with the t(4;11) translocation predominating among acute lymphoblastic leukemias, and the t(9;11), t(11;19) and t(6;11) translocations most common among acute myeloid leukemias. In each of these translocations the ALL-1 gene, located at 11q23 and constituting the human homologue of Drosophila trithorax, fuses to a specific gene on the partner chromosome to produce a chimeric protein. Here we report the cloning and the characterization of the partner gene from chromosome 6 (AF-6). AF-6 is expressed in a variety of cell types and encodes a protein of 1612 amino acids. The protein contains short stretches rich in prolines, charged amino acids, serines, or glutamines. In addition, the AF-6 protein contains the GLGF motif shared with several proteins of vertebrates and invertebrates thought to be involved in signal transduction at special cell-cell junctions.

Amino Acid Sequence↗

Expression of c-fos in brain subcortical structures in response to nauseant lithium chloride and osmotic pressure in rats.

Immunohistochemistry was used to map c-fos expression in rats to investigate the neural substrates that mediate the emetic action of lithium chloride and the effect of osmotic pressure. Solutions of 3% lithium chloride or 4.14% saline, isotonic to each other, as well as 0.65% lithium chloride or 0.9% saline, also isotonic to each other, were administered intraperitoneally (3 ml/kg) in rats. Both lithium chloride and osmotic pressure enhanced c-fos expression in the nuclei of the solitary tract, the paraventricular nuclei and supraoptic nuclei of the hypothalamus, and in the amygdala. This suggests that these brain structures might be the sites where the autonomic, neuroendocrine and behavioral responses elicited by lithium chloride and osmotic pressure are integrated.

Animals↗

Analysis of the murine All-1 gene reveals conserved domains with human ALL-1 and identifies a motif shared with DNA methyltransferases.

A series of translocation break points found in a subset of human acute leukemias have one of the breaks on human chromosome 11q23. This region has recently been cloned and a large gene, ALL-1, with homology to the Drosophila trithorax gene has been identified. This paper describes the cloning, sequencing, and mapping of the mouse homolog of ALL-1. We have found a motif present in All-1 that shows homology to the zinc-binding domain of DNA (cytosine-5) methyltransferases (EC 2.1.1.63). Sequence analysis of the murine All-1 gene has identified distinct regions of homology with the human ALL-1 gene; these highly conserved domains may define regions of functional significance in mammals. In addition, we have identified alternatively spliced forms of All-1 within one of the zinc-finger domains, suggesting that there may be different targets and/or functions for All-1 proteins. Finally, we report that All-1 resides in the proximal portion of mouse chromosome 9 and is a candidate for a mutation that results in skeletal transformations during embryonic development.

Alternative Splicing↗

Genes on chromosomes 4, 9, and 19 involved in 11q23 abnormalities in acute leukemia share sequence homology and/or common motifs.

Chromosome translocations involving band 11q23 are associated with human acute leukemias. These translocations fuse the ALL-1 gene, homolog of Drosophila trithorax and located at chromosome band 11q23, to genes from a variety of chromosomes. We cloned and sequenced cDNAs derived from transcripts of the AF-4 and AF-9 genes involved in the most common chromosome abnormalities, t(4:11)(q21:q23) and t(9:11)(p22:q23), respectively. Sequence analysis indicates high homology between the AF-9 gene protein product and the protein encoded by the ENL gene fused to ALL-1 in (11:19) chromosome translocations. AF-4, AF-9, and ENL proteins contain nuclear targeting sequences as well as serine-rich and proline-rich regions. Stretches abundant in basic amino acids are also present in the three proteins. These results suggest that the different proteins fused to ALL-1 polypeptide(s) provide similar functional domains.

Acute Disease↗

The induction and suppression of c-fos expression in the rat brain by cholecystokinin and its antagonist L364,718.

Immunohistochemical techniques were used to map c-fos expression in the rat brain after the i.p. administration of CCK-8 (8 micrograms/kg). C-fos expression was observed in the rostral and the caudal parts of the nuclei of the solitary tract (NTS), and the paraventricular nuclei (PVN) in the hypothalamus. The c-fos expression in these areas was suppressed by the administration of L364,718 (120 micrograms/kg). Since L364,718 is known to be a powerful selective antagonist to the peripheral CCK-A receptors, these data suggest that the effects produced by exogenous CCK are due to peripheral receptors that project to the NTS.

Animals↗

In vitro uptake and autoradiographic localization of tritiated gossypol in Taenia taeniaeformis metacestodes.

Gossypol, a natural polyphenolic compound, induces growth-inhibitory and antiparasitic effects in Taenia taeniaeformis metacestodes in vivo and in vitro. We investigated the uptake and localization of [3H]-gossypol in this parasite. Metacestodes were incubated in 10(-5) M [3H]-gossypol at 37 degrees C. Parasites steadily took up tritium activity over the first 3 h of incubation, after which a plateau was maintained for the duration of the experiment. Tissue: medium radioactivity ratios revealed that intralarval tritium activity matched extralarval activity within 30 min of incubation and continued to increase with time. Reverse-phase high-performance liquid chromatographic (HPLC) analysis confirmed tissue incorporation of tritium activity that manifested as a single radioactive species. Autoradiography localized [3H]-gossypol to the tegument, calcareous corpuscles, and parenchyma over the first 2 h of incubation. By 6 h, parenchymal radioactivity had disappeared. T. taeniaeformis metacestodes rapidly take up and accumulate [3H]-gossypol in vitro. This accumulation is apparently selective for specific sites, which may have implications for gossypol's metacestocidal action.

Animals↗

Early and early disseminated phases of Lyme disease in the rhesus monkey: a model for infection in humans.

We demonstrate that Borrelia burgdorferi infection in the rhesus monkey mimics the early and early disseminated phases of human Lyme disease. Clinical, bacteriological, immunological, and pathological signs of infection were investigated during 13 weeks after inoculation of the spirochete. Three animals were given B. burgdorferi (strain JD1) by needle inoculations, six animals were exposed to the bite of B. burgdorferi-infected Ixodes dammini ticks, and three animals were uninfected controls. B. burgdorferi could be recovered from all animals that were given the spirochete. Bacteria were detectable until week 6 postinoculation (p.i.) in blood, until week 8 p.i. in skin biopsies, and at 10 weeks p.i. in the conjunctiva of one of two animals which developed conjunctivitis. Erythema migrans (EM) appeared in one of the three animals infected by needle inoculation and in five of the six animals infected by ticks. Deep dermal perivascular lymphocytic infiltrations (characteristic of human EM) were observed in all animals showing EM clinically. Both EM and conjunctivitis were documented concomitantly with the presence of the spirochete. Lethargy, splenomegaly, and cerebrospinal fluid pleocytosis were also noted in some animals, but the direct connection of these signs with the infection was not shown. The appearance rate of immunoglobulin M and immunoglobulin G antibodies to B. burgdorferi, as well as the antigen spectra recognized, were remarkably similar to those seen in humans. Serum antibodies from infected animals were able to kill B. burgdorferi in vitro in the presence of rhesus complement. The rhesus monkey model appears to be useful for the investigation of the immunology and pathogenesis of Lyme disease and for the development of immunoprophylactic, diagnostic, and chemotherapeutic protocols.

Animals↗

Assessment of left ventricular diastolic function and potential by quantitative analysis of left ventricular filling curves in patients with atrial fibrillation. A new algorithm for Doppler echocardiographic study.

To evaluate left ventricular (LV) diastolic function and potential, LV filling curves for 18 patients with atrial fibrillation (Af) were constructed and their positions and appearance were evaluated quantitatively by analysis of 95% maximal filling volume points and maximal curvature alteration points. The LV filling curves of group A (Af only) lay left superiorly, while those of group B (impaired LV diastolic function) were situated right inferiorly, all bending steeply. The LV filling curves of group C (mitral stenosis) bent slightly. The lowest normal filling volume points and compensation areas were calculated to evaluate LV diastolic function and were demonstrated to be very different in groups A and B. The lowest normal filling volume points of group C were similar to those of group A, but compensation areas were smaller, indicating a lower LV diastolic potential. It is concluded that the 95% maximal filling volume point, maximal curvature alteration point, lowest normal filling volume point and compensation area are effective indices for evaluating not only LV diastolic function but also the diastolic potential.

Algorithms↗

Chronic effects of camostate on growth and endocrine function of the pancreas in streptozotocin-induced diabetic rats.

Chronic feeding of normal rats with camostate, a synthetic trypsin inhibitor, stimulates the growth of the pancreas chiefly by increasing cholecystokinin release. We examined the effects of camostate on the growth and the endocrine function of the pancreas in streptozotocin-induced diabetic rats. The pancreatic weight of the diabetic rats given camostate (200 mg/kg/day) by oral gavage for 14 days was significantly elevated by 120% over that of diabetic rats not given camostate, and was comparable to that in the nondiabetic rats given camostate. The total pancreatic contents of DNA, RNA, and protein in diabetic rats given camostate were also significantly higher than those in diabetic rats not given camostate, and did not differ from those observed in nondiabetic rats given camostate. The pancreatic growth seen in diabetic rats treated with camostate was associated with moderate hyperplasia and pronounced hypertrophy. By contrast, treatment with camostate did not improve hyperglycemia, hypoinsulinemia, or low pancreatic content of insulin seen in diabetic rats. These findings demonstrate a marked growth of the pancreas in diabetic rats stimulated by camostate, and suggest that camostate-induced pancreatic growth is not affected by the reduced level of the endogenous insulin. The present study also indicates that camostate has no beneficial effects on the function of residual B cells, failing to improve diabetes.

Animals↗

The t(4;11) chromosome translocation of human acute leukemias fuses the ALL-1 gene, related to Drosophila trithorax, to the AF-4 gene.

The ALL-1 gene located at human chromosome 11 band q23 is rearranged in acute leukemias with interstitial deletions or reciprocal translocations between this region and chromosomes 1, 4, 6, 9, 10, or 19. The gene spans approximately 100 kb of DNA and contains at least 21 exons. It encodes a protein of more than 3910 amino acids containing three regions with homology to sequences within the Drosophila trithorax gene, including cysteine-rich regions that can be folded into six zinc finger-like domains. The breakpoint cluster region within ALL-1 spans 8 kb and encompasses several small exons, most of which begin in the same phase of the open reading frame. The t(4;11) chromosome translocation results in two reciprocal fusion products coding for chimeric proteins derived from ALL-1 and from a gene on chromosome 4. This suggests that each 11q23 abnormality gives rise to a specific oncogenic fusion protein.

Amino Acid Sequence↗

The (4;11)(q21;q23) chromosome translocations in acute leukemias involve the VDJ recombinase.

Chromosomal region 11q23 is frequently rearranged in acute lymphocytic leukemias (ALLs) and in acute myeloid leukemias (AMLs), mostly in reciprocal exchanges with various translocation partners. The most common of these translocations is t(4;11)(q21;q23). It is present in approximately 10% of ALL patients, most frequently in very young children. We have recently cloned a region of chromosome 11, the ALL-1 locus, found to be rearranged in malignant cells from patients with the t(4;11), t(9;11), t(11;19), t(1;11), t(6;11), t(10;11), and del(11q23) chromosomal abnormalities. Here we report the cloning and characterization of chromosomal breakpoints from leukemic cells with t(4;11) aberrations. The breakpoints cluster in regions of 7-8 kilobases on both chromosomes 4 and 11. The presence of heptamer- and nonamer-like sequences at the sites of breakage suggests that the VDJ recombinase utilized for immunoglobulin gene rearrangement is also directly involved in these translocations. We also show that leukemic cells with t(4;11) express altered RNAs transcribed from the derivative chromosomes 11 and 4.

Acute Disease↗

Nerve growth factor promotes collateral sprouting of cholinergic fibers in the septohippocampal cholinergic system of aged rats with fimbria transection.

Nerve growth factor (NGF) was injected intraventricularly into aged (24 months) rats with unilateral fimbria transection. Controls received intraventricular injections of cytochrome c. A quantitative analysis of acetylcholinesterase (AChE)-positive fibers was used to evaluate whether the NGF treatment can stimulate regeneration and reinnervation of the cholinergic axons in the septohippocampal system of aged rats with fimbria transection. A marked increase in the density of AChE-positive fibers was observed in the lateral septum, the dorsal fornix and the dorsal hippocampus of the NGF-treated animals, as compared to the controls. In the lateral septum, the increase was observed in the 2-month NGF-treated animals but not in the 15-day NGF-treated animals. In the dorsal fornix at the level of the dorsal hippocampus, the increase was observed on both the lesioned and unlesioned sides of both the 15-day and 2-month NGF-treated animals. In the denervated (lesioned side) hippocampus, the increase took place in the dorsal hippocampus but not in the ventral hippocampus of both the 15-day and 2-month NGF-treated animals. There was no recovery of AChE-positive fibers on the lesioned side of the fimbria distal to the lesion site even in the 2-month NGF-treated animals. These results demonstrate that intraventricular injections of NGF can stimulate collateral sprouting of intact cholinergic axons in the septohippocampal system and promote cholinergic reinnervation of the denervated hippocampus of aged rats with fimbria transection.

Acetylcholinesterase↗