Gut reaction to Wnt signaling in worms.
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Animals↗
Biomedical subjects
M Han
Publications and source records attributed to M Han.
The steric trigger in rhodopsin activation.
Rhodopsin is the seven transmembrane helix receptor responsible for dim light vision in vertebrate rod cells. The protein has structural homology with the other G protein-coupled receptors, which suggests that the tertiary structures and activation mechanisms are likely to be similar. However, rhodopsin is unique in several respects. The most striking is the fact that the receptor "ligand", 11-cis retinal, is covalently bound to the protein and is converted from an "antagonist" to an "agonist" upon absorption of light. NMR studies of rhodopsin and its primary photoproduct, bathorhodopsin, have generated structural constraints that enabled docking of the 11-cis and all-trans retinal chromophores into a low-resolution model of the protein proposed by Baldwin. These studies also suggest a mechanism for how retinal isomerization leads to rhodopsin activation. More recently, mutagenesis studies have extended these results by showing how the selectivity of the retinal-binding site can be modified to favor the all-trans over the 11-cis isomer. The structural constraints produced from these studies, when placed in the context of a high-resolution model of the protein, provide a coherent picture of the activation mechanism, which we show involves a direct steric interaction between the retinal chromophore and transmembrane helix 3 in the region of Gly121.
Amino Acid Sequence↗
Ras is required for a limited number of cell fates and not for general proliferation in Caenorhabditis elegans.
Experiments with mammalian tissue culture cells have implicated the small GTPase Ras in the control of cellular proliferation. Evidence is presented here that this is not the case for a living animal, the nematode Caenorhabditis elegans: proliferation late in embryogenesis and throughout the four larval stages is not noticeably affected in animals lacking Ras in various parts of their cell lineages. Instead, genetic mosaic analysis of the let-60 gene suggests that Ras is required only, at least later in development (a maternal effect cannot be excluded), for establishment of a few temporally and spatially distinct cell fates. Only one of these, the duct cell fate, appears to be essential for viability.
Animals↗
Application of liposomes for development of oral vaccines: study of in vitro stability of liposomes and antibody response to antigen associated with liposomes after oral immunization.
In order to evaluate the usefulness of liposomes as oral vaccines, the stability of liposomes and serum IgA antibody response to antigen associated with liposomes after oral administration were examined. Liposomes composed of dipalmitoylphosphatidylcholine (DPPC), dipalmitoylphosphatidylserine (DPPS), and cholesterol (Chol) (1:1:2, molar ratio), distearoylphosphatidylcholine (DSPC) and Chol (7:2, molar ratio), and DSPC, DPPS, and Chol (7:3:2 or 1:1:2, molar ratio) were stable in acidic solution (pH 2.0), bile, and pancreatin solution, whereas liposomes composed of DPPC and Chol (7:2, molar ratio) and DPPC, DPPS, and Chol (7:3:2, molar ratio) were unstable in pH 2.0 and/or bile solutions. After the oral immunization of antigen (ganglioside GM1)-containing liposomes composed of DPPC, DPPS, and Chol (1:1:2, molar ratio) to mice, the serum IgA antibody responses against ganglioside GM1 were found. Furthermore, when monophosphoryl lipid A was incorporated into liposomes containing ganglioside GM1, further augmentation of IgA responses to ganglioside GM1 was observed. On the other hand, the oral administration with liposomes composed of DPPC, Chol, and ganglioside GM1 (unstable liposomes), ganglioside GM1 mixed with liposomes composed of DPPC, DPPS and Chol, and ganglioside GM1 alone was unable to induce any detectable anti-ganglioside GM1 IgA antibody responses. These results suggest that liposomes which showed the stability to acidic solution, bile, and pancreatin solution would serve effectively as an oral delivery vehicle for inducing mucosal immune responses.
Administration, Oral↗
[Surgical treatment in pulmonary tuberculosis with sputum long-term Mycobacterium tuberculosis positive].
OBJECTIVE: To evaluate the importance of surgical treatment in pulmonary tuberculosis with sputum long-term Mycobacterium tuberculosis positive. METHOD: Sixty-five patients with pulmonary tuberculosis who failed antituberculosis chemotherapy received lung resection or thoracoplasty. RESULT: Sputum negative conversion was found in sixty-three patients without recurrence during 1-3 year follow-up, while sputum positive conversion was found only in one case during the period of follow-up. Among all the patients, one died of respiratory failure after the operation, three complicated with empyema and recovered from operating again. CONCLUSION: Surgical operation is still important for treating pulmonary tuberculosis patients with sputum long-term Mycobacterium tuberculosis positive.
Adolescent↗
[An approach to the binocular vision of traumatic cataract after intraocular lens implantation].
OBJECTIVE: To explore the recovery of binocular vision and stereoacuity of monocular cataract extraction after posterior chamber intraocular lens (IOL) implantation. METHODS: After extraction of traumatic cataract, primary or secondary posterior chamber IOL implantation was performed on 36 cases. The naked vision, corrected vision and binocular dioptric state were observed pre- and post-operatively. Synoptophore, Bogolini striated glasses, barred reading and Tiemus stereoscopic vision picture were applied. RESULTS: The visual acuities of 36 cases were significantly improved postoperatively, the corrected visual acuities of 24 cases (66.7%) were over 4.95 and 30 cases were over 4.8 after three months. The binocular and stereoscopic vision of 21 cases was recovered well. CONCLUSION: IOL implantation should be performed early after extraction of monocular cataract in order to improve the recovery and development of binocular vision and stereoacuity, particularly in children.
Adolescent↗
[Effects of IFN-alpha on the expressions of perforin and granzymes in IL-2 activated lymphocytes].
OBJECTIVE: To study the effect of IFN-alpha on the expressions of perforin and granzymes in IL-2-activated-lymphocytes. METHODS: NK and LAK activities were assayed by 4 hour standard 51Cr release test, the activity of perforin was detected by hemolysis method, expression of granzyme B was measured by ABC immunohistological method, expression of granzyme A was measured by BLT method. RESULTS: IFN-alpha significantly augmented the activities of NK and LAK in IL-2 activated peripheral blood lymphocytes (PBL) after 1 day culture. Perforin activity in lymphocytes was increased after 1 day exposure to IL-2 or IFN-alpha, and was enhanced when exposed to the combination of IL-2 and IFN-alpha. After 3 day culture, the perforin activity remained high in lymphocytes activated by IL-2 alone or in combination with IFN-alpha, while declined to control level in IFN-alpha exposed group. IL-2 and IFN-alpha alone or in combination had no effect on expression of granzyme A and B. CONCLUSION: IFN-alpha enhances the cytotoxicity of lymphocytes activated by IL-2. The mechanism might be that IFN-alpha upregulates the perforin expression.
Gene Expression Regulation↗
[In vitro reversal of homoharringtonine resistance by the combination of tamoxifen and verapamil].
OBJECTIVE: To investigate the reversal of homoharringtonine (HHT)-resistance by tamoxifen (TAM) or verapamil (VER) alone or in combination. METHODS: The drug-sensitivity test was performed with semisolid agar culture. RESULTS: The cytotoxicity of HHT to K562/S cells was not enhanced by TAM or VER alone or in combination,but HHT resistance in HHT resistant cells (K562/H20) was reversed by VER and TAM at nontoxic doses (4micromol/L or 8micromol/L). The IC50 of K562/H20 for HHT decreased from 446.8 +/- 0.08microg/L to 45.1 +/- 0.02microg/L in the presence of 4micromol/L of VER, to 22.4 +/- 0.03microg/L in 8micromol/L of VER, to 85.1 +/- 0.03microg/L in 4micromol/L of TAM and to 26.4 +/- 0.02microg/L in 8micromol/L of TAM. In the presence of combinations of 2micromol/L VER and 4micromol/L TAM and of 2micromol/L VER and 8micromol/L TAM, IC50 of K562/H20 decreased to 30.4 +/- 0.02microg/L and 4.3 +/- 0.04microg/L, respectively. CONCLUSION: HHT-resistance could be reversed by VER or TAM alone, and the combination of the two drugs showed a synergistic effect.
Animals↗
[Effect of bone marrow transplantation conditioning regimen on thyroid and adrenocortical functions in patients with blood diseases].
OBJECTIVE: In order to investigate the life quality of patients with hematological diseases after bone marrow transplantation (BMT). METHODS: Pituitary-thyroid and adrenocortical function were de tected in 29 patients with hematological diseases before and after BMT. RESULTS: All patients had normal thyroid and adrenocortical functions before BMT. As compared with pre-BMT,the median serum TSH levels were significantly increased at 3, 6, 12 (P<0.01), 24-60 (P<0.05) months post-BMT. The adrenocortical function had no change in all patients, and thyroid dysfunction were found in 6 of 24 patients detected at a median time of 6 month post-BMT. Five of the 6 thyroid dysfuntion patients developed hypothyroidism, and one hyperthyroidism. CONCLUSION: There was little effect of conditioning regimen on adrenocortical function, while thyroid dysfunction was common after BMT. Long term follow up on thyroid function in patients after BMT is necessary.
Adolescent↗
[Studies on expansion ex vivo of murine bone marrow cells and its hematopoietic reconstitution capacity].
OBJECTIVE: To investigate the effects of stem cell factor (SCF) in combination with interleukin-1 (IL-1) or/and interleukin-3 (IL-3) on ex vivo expansion of 5FU treated bone marrow cells and hematopoietic recovery in lethally irradiated mice transplanted with the expanded cells. METHODS: 5FU treated bone marrow cells (d3-5FU-BMC) were cultured in a cytokines-containing medium, and the net increments of CFU-GM and high proliferative potential colony forming cell (HPP-CFC) were evaluated. RESULTS: CFU-GM increased by 33.7 +/- 18.1- or 18.1 +/- 6.3- fold, and HPP-CFC by 17.8 +/- 10.5- or 12.7 +/- 9.1- fold, respectively, in cultures containing SCF with IL- or IL-3, as compared with that in control; while SCF alone had little effect. Compared with fresh d3-5FU-BMC, transplantation of the expanded bone marrow cells accelerated the recovery of recipients' peripheral blood cell counts by 1 approximately 3 days and increased the survival rate of the transplanted animals (d3-5FU-BMC group 50% vs expansion group 8U approximately 100%). CONCLUSION: SCF in combination with IL-1 or IL-3 synergetically ex vivo expands hematopoietic cells. Transplantation of the expanded bone marrow cells accelerates the recipient's hematopoietic reconstitution.
Animals↗
The natural history and treatment of adrenal myelolipoma.
PURPOSE: We determined the natural history and clarified the treatment of adrenal myelolipoma. MATERIALS AND METHODS: A retrospective review of medical records and radiographic imaging studies of 20 patients diagnosed with adrenal myelolipoma was performed. RESULTS: Of 20 patients 4 presented with abdominal pain and 1 had Cushing's syndrome. The remaining tumors were discovered incidentally. Four patients underwent surgery because of abdominal pain in 2, adrenal hyperfunction (Cushing's syndrome) in 1 and a tumor 10.5 cm. in largest dimension in 1. Of 15 patients (16 adrenal myelolipomas) followed without surgical intervention for an average of 3.2 years (range 0.3 to 10.8) 13 remained asymptomatic and 2 experienced persistent, vague abdominal discomfort. One patient was lost to followup. A total of 13 tumors from 12 patients was serially imaged, with tumor size increasing in 6, decreasing in 2 and remaining unchanged in 5. CONCLUSIONS: These data suggest that the majority of adrenal myelolipomas can be treated conservatively. While tumors can become enlarged, they also exhibit variable growth, and size and growth rate do not necessarily correlate with symptoms. Computerized tomography can be used for diagnosis.
Adrenal Gland Neoplasms↗
[Relationship between human parvovirus B19 infection and spontaneous abortion].
OBJECTIVE: To determine whether there is a relationship between parvovirus B19 infection and spontaneous abortion. METHODS: 105 embryo tissues from spontaneous abortions of unknown cause during 1994-1995 were studied using nested polymerase chain reaction (PCR) assay for parvovirus B19 DNA. As controls 40 fetal tissues were also examined. Among which, 20 were collected from induced abortions, and the others were stillbirths. The positive specimens underwent further study for TORCH infections. RESULTS: 26 (24.5%) were B19 DNA positive in the case group and 2 (5.0%) in the control group. The difference was significant (P < 0.05). Among 26 positive specimens, 5 had cytomegalovirus (CMV) infection as well as 2 had both CMV and herpes simplex virus (RSV) infections. CONCLUSIONS: Parvovirus B19 infection may be an important pathogen for spontaneous abortion, and it is suggested to investigate parvovirus B19 infection among pregnant women in China.
Abortion, Spontaneous↗
[Effect of adrenomedullin on mesenteric microvessels and microlymphatics in rat].
The dilatant effect of adrenomedullin (ADM), a novel peptide of 52 amino acids, on the mesenteric microvessels and microlymphatics was investigated under microscopic observation. 10(-6) mol/L ADM could also ameliorate alteration of the hemorheology induced by 10(-5) mol/L norepinephrine (NE) or 10(-7) mol/L endothelin (ET). However, this ameliorative response was markedly inhibited in the presence of NG-nitro-L-arginine (L-NNA), an inhibitor for production of nitric oxide.
Adrenomedullin↗
The effects of amino acid replacements of glycine 121 on transmembrane helix 3 of rhodopsin.
Rhodopsin is a member of a family of G protein-coupled receptors with seven transmembrane (TM) helices. In rhodopsin, Gly121 is a highly conserved amino acid residue near the middle of TM helix 3. TM helix 3 is known to be involved in chromophore-protein interactions and contains the chromophore Schiff base counterion at position 113. We prepared a set of seven single amino acid replacement mutants of rhodopsin at position 121 (G121A, Ser, Thr, Val, Ile, Leu, and Trp) and control mutants with replacements of Gly114 or Ala117. The mutant opsins were expressed in COS cells and reconstituted with either 11-cis-retinal, the ground-state chromophore of rhodopsin, or all-trans-retinal, the isomer formed upon receptor photoactivation. The replacement of Gly121 resulted in a relative reversal in the selectivity of the opsin apoprotein for reconstitution with 11-cis-retinal over all-trans-retinal in COS cell membranes. The mutant pigments also were found to be thermally unstable to varying degrees and reactive to hydroxylamine in the dark. In addition, the size of the residue substituted at position 121 correlated directly to the degree of blue-shift in the lambdamax value of the pigment. These results suggest that Gly121 is an important and specific component of the 11-cis-retinal binding pocket in rhodopsin.
Amino Acid Sequence↗
Functional interaction of transmembrane helices 3 and 6 in rhodopsin. Replacement of phenylalanine 261 by alanine causes reversion of phenotype of a glycine 121 replacement mutant.
Replacement of a highly conserved glycine residue on transmembrane (TM) helix 3 of bovine rhodopsin (Gly121) by amino acid residues with larger side chains causes a progressive blue-shift in the lambdamax value of the pigment, a decrease in thermal stability, and an increase in reactivity with hydroxylamine. In addition, mutation of Gly121 causes a relative reversal in the selectivity of opsin for 11-cis-retinal over all-trans-retinal. It was suggested that Gly121 plays an important role in defining the 11-cis-retinal binding pocket of rhodopsin (Han, M., Lin, S. W., Smith, S. O., and Sakmar, T. P. (1996) J. Biol. Chem. 271, 32330-32336). Here, we combined the mutant opsin G121L with second site replacements of four different amino acid residues on TM helix 6: Met257, Val258, Phe261, or Trp265. We show that the loss of function phenotypes of the G121L mutant described above can be partially reverted specifically by the mutation of Phe261, a residue highly conserved in all G protein-coupled receptors. For example, the double-replacement mutant G121L/F261A has spectral, chromophore-binding, and transducin-activating properties intermediate between those of G121L and rhodopsin. This rescue of the G121L defects did not occur with the other second site mutations tested. We conclude that specific portions of TM helices 3 and 6, which include Gly121 and Phe261, respectively, define the chromophore-binding pocket in rhodopsin. Finally, the results are placed in the context of a molecular graphics model of the TM domain of rhodopsin, which includes the retinal-binding pocket.
Alanine↗
[The effect of brain-derived neurotrophic factor on regeneration of nerve fibers after crush injury--morphometric evaluation].
Brain-derived neurotrophic factor (BDNF) is produced in Schwann cells and fibroblasts in the peripheral nerve, and is considered to play an important role in survival, maintenance, development and repair of the peripheral neuron. In this study, the effect of human recombinant BDNF on the regeneration of nerve fibers following a crush injury to the sciatic nerves of Sprague-Dawley rats was evaluated. In the experimental group, 20 mg/kg of BDNF was injected subcutaneously three times a week for 4 weeks in seven rats. In the control group, only the dissolving solution used in the experimental group was injected similarly in seven rats as in the experimental group. The various morphometric parameters were evaluated in the peroneal, sural and tibial nerves and the nerve to soleus muscle distal to the crush site. There were no statistically significant differences in the change of body weight, the improvement of the width between the first and fifth toes on the side of the crush, the density of total myelinated fibers (numbers per mm2), the total number of myelinated fibers (number per nerve), maximum and median diameters of myelinated fibers, the density of unmyelinated fibers, and the electron microscopic parameters of axon and myelin sheath. On the other hand, the number of myelin lamellae in relation to the transverse axonal area was significantly greater in the experimental group than in the control group. Therefore, BDNF may promote the myelination. However, such an effect on myelination seems not to be clinically significant, because such an effect was not demonstrated in other morphometric evaluations reflecting the myelination condition. Therefore, taking all the data obtained in this study into consideration, we concluded that there was no definite evidence that BDNF promoted the regeneration of nerve fibers at least under these experimental conditions.
Animals↗
D-Lysergyl peptide synthetase from the ergot fungus Claviceps purpurea.
The ergot fungus Claviceps purpurea produces the medically important ergopeptines, which consist of a cyclol-structured tripeptide and D-lysergic acid linked by an amide bond. An enzyme activity capable of non-ribosomal synthesis of D-lysergyl-L-alanyl-L-phenylalanyl-L-proline lactam, the non-cyclol precursor of the ergopeptine ergotamine, has been purified about 18-fold from the ergotamine-producing C. purpurea strain D1. Analysis of radioactively labeled enzyme-substrate complexes revealed a 370-kDa lysergyl peptide synthetase 1 (LPS 1) carrying the amino acid activation domains for alanine, phenylalanine, and proline. The activation of D-lysergic acid is catalyzed by a 140-kDa peptide synthetase (LPS 2) copurifying with LPS 1. LPS 1 and LPS 2 contain 4'-phosphopantetheine and bind their substrates covalently by thioester linkage. Kinetic analysis of the synthesis reaction revealed a Km of approximately 1.4 microM for both D-lysergic acid and its structural homolog dihydrolysergic acid, which is one to two orders of magnitude lower than the Km values for the other amino acids involved. The Km values for the amino acids reflect their relative concentrations in the cellular pool of C. purpurea. This may indicate that in in vivo conditions D-lysergyl peptide formation is limited by the D-lysergic acid concentration in the cell. In vitro, the multienzyme preparation catalyzes the formation of several different D-lysergyl peptide lactams according to the amino acids supplied. Specific antiserum was used to detect LPS 1 in various C. purpurea strains. In C. purpurea wild type, the enzyme was expressed at all stages of cultivation and in different media, suggesting that it is produced constitutively.
Amino Acids↗
Neurosteroid analogues. 4. The effect of methyl substitution at the C-5 and C-10 positions of neurosteroids on electrophysiological activity at GABAA receptors.
A series of analogues of the neuroactive steroids 3 alpha-hydroxy-5 alpha-pregnan-20-one and 3 alpha-hydroxy-5 beta-pregnan-20-one were studied to elucidate the mode of binding of 5 alpha-and 5 beta-reduced steroids to steroid binding sites on GABAA receptors. Analogues which were either 3 alpha-hydroxy-20-ketosteroids or 3 alpha-hydroxysteroid-17 beta-carbonitriles and which contained various methyl group substitution patterns at C-5 and C-10 were prepared. Evaluations utilized whole-cell patch clamp electrophysiological methods carried out on cultured rat hippocampal neurons, and the results obtained with the rigid 17 beta-carbonitrile analogs were analyzed using molecular modeling methods. The molecular modeling results provide a rationale for the observation that the configuration of the hydroxyl group at C-3 is a greater determinant of anesthetic potency than the configuration of the A,B ring fusion at C-5. The electrophysiological results identify steric restrictions for the space that can be occupied in 5 alpha- and 5 beta-reduced steroid modulators of GABAA receptors in the regions of space proximate to the steroid C-5, C-10, and possibly C-4 positions. This information is useful for the development of nonsteroidal analogues that can modulate GABAA receptors via interactions at steroid binding sites.
Animals↗