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Biomedical subjects

C Ma

Publications and source records attributed to C Ma.

At least 73 records · Page 4Linked to original sources

Characterization of an experimentally induced inner ear immune response.

OBJECTIVE: To determine the effects of a sterile immune response on the structure and function of the cochlea. METHODS: An immune response was created in guinea pigs by systemically sensitizing the animals to keyhole limpet hemocyanin and subsequently challenging the inner ear with the protein. Animals were allowed to survive for 1 to 5 weeks, after which the cochlea was evaluated histologically. Hearing was measured by auditory brainstem response before the inner ear challenge, during the survival period, and prior to sacrifice. RESULTS: Inflammatory cells infiltrated the cochlea from the circulation. Surface preparations and plastic sections of the organ of Corti 1 and 2 weeks after the initiation of the inflammation demonstrated degeneration of the sensory and supporting cells in cochlear turns containing inflammatory cells. Good preservation of structures was seen in the more apical cochlear turns with little or no inflammatory cells. In cochleas from animals that survived 5 weeks, most of the infiltrated cells were cleared after undergoing apoptosis and the inflammatory matrix in the scala tympani began to calcify. Hearing loss was moderate to severe depending on the amount of inflammation. CONCLUSION: Although in general the immune response serves to protect an organism from infection, these results demonstrate that bystander injury associated with local immune responses in the cochlea, an organ incapable of regeneration, causes permanent cochlear destruction and hearing loss.

Adjuvants, Immunologic↗

Point mutations in a peptidoglycan biosynthesis gene cause competence induction in Haemophilus influenzae.

We have identified three new Haemophilus influenzae mutations causing cells to exhibit extreme hypercompetence at all stages of growth. The mutations are in murE, which encodes the meso-diaminopimelate-adding enzyme of peptidoglycan synthesis. All are point mutations causing nonconservative amino acid substitutions, two at a poorly conserved residue (G(435)-->R and G(435)-->W) and the third at a highly conserved leucine (L(361)-->S). The mutant strains have very similar phenotypes and do not exhibit any defects in cell growth, permeability, or sensitivity to peptidoglycan antibiotics. Cells retain the normal specificity of DNA uptake for the H. influenzae uptake signal sequence. The mutations do not bypass genes known to be needed for competence induction but do dramatically increase expression of genes required for the normal pathway of DNA uptake. We conclude that the mutations do not act by increasing cell permeability but by causing induction of the normal competence pathway via a previously unsuspected signal.

Amino Acid Sequence↗

Similarity in the linear and non-linear oral absorption of drugs between human and rat.

OBJECTIVE: The main aim of this study was to provide a simple, pharmacokinetic rationale for great similarity in the extent (Fab) of gastrointestinal absorption of about 100 different, diverse compounds between human and the rat in linear dosing range, and to test the general applicability of a novel empirical method to correlate the non-linear Fab between the human and the rat by normalizing doses by body surface area (BSA) or body weight 0.67. METHOD: The mean small intestinal transit time (t) of 36 rats was estimated from the reported study, and this was used to compare with that in humans. The reported great similarity in apparent first-order absorption rate constants (k) of seven structurally diverse compounds between the two species were obtained. Extensive computer search was made and non-linear Fab data for the two species were obtained for chlorothiazide, acyclovir, miglitol and pafenolol. RESULTS: The mean t for rats was estimated to be 3.32 h which is almost identical to that reported in humans. The great similarity in Fab between human and rat in linear absorption range can be rationalized by similar t and k between the two species. The markedly different Fab vs dose/kg of body weight profiles between human and rat for the four drugs showing dose-dependent Fab were found to collapse when doses were normalized by BW0.67. CONCLUSION: For Fab not limited by the solubility problem, the great similarity in Fab between human and rat in linear absorption range can be rationalized by the similar t and k. For non-linear Fab drugs, great similarity in Fab can also be obtained between human and rat when doses are normalized by BSA or BW0.67. Regardless of absorption properties (active, passive or facilitated), similar Fab between the two species may be generally obtained when doses used in humans are about 5 to 7 times lower than that in rats. The above findings may be valuable in drug development.

1-Deoxynojirimycin↗

Use of carnosine as a natural anti-senescence drug for human beings.

Carnosine is an endogenous free-radical scavenger. The latest research has indicated that apart from the function of protecting cells from oxidation-induced stress damage, carnosine appears to be able to extend the lifespan of cultured cells, rejuvenate senescent cells, inhibit the toxic effects of amyloid peptide (A beta), malondialdehyde, and hypochlorite to cells, inhibit glycosylation of proteins and protein-DNA and protein-protein cross-linking, and maintain cellular homeostasis. Also, carnosine seems to delay the impairment of eyesight with aging, effectively preventing and treating senile cataract and other age-related diseases. Therefore, carnosine may be applied to human being as a drug against aging.

Aging↗

Pharmacophore/receptor models for GABA(A)/BzR alpha2beta3gamma2, alpha3beta3gamma2 and alpha4beta3gamma2 recombinant subtypes. Included volume analysis and comparison to alpha1beta3gamma2, alpha5beta3gamma2, and alpha6beta3gamma2 subtypes.

Pharmacophore/receptor models for 6 recombinant GABA(A)/BzR subtypes (alphax beta3gamma2, x = 1-6) have been established via an SAR ligand mapping approach. This study was based on the affinities of 166 BzR ligands at 6 distinct (alpha1-6beta3gamma2) recombinant GABA(A)/BzR receptor subtypes from at least twelve different structural families. Examination of the included volumes indicated that the shapes of binding pockets for alpha1, alpha2 and alpha3 subtypes are very similar to each other. Region L2 for the alpha5 containing subtype appeared to be larger in size than the analogous region of the other receptor subtypes. Region L(Di), in contrast, appeared to be larger in the alpha1 subtype than in the other subtypes. Moreover, region L3 in the alpha6 subtype is either very small or nonexistent in this diazepam insensitive "DI" subtype as compared to the other subtypes. Preliminary results for the alpha4-containing receptor subtype (DI) indicate that L3 in the alpha4 subtype suffers a similar fate. Use of the pharmacophore/receptor models for these subtypes have resulted in the design of novel BzR ligands selective for the alpha5beta3gamma2, receptor subtype.

Animals↗

[Clinical and experimental studies on clearing away stomach-heat purging fire and nourishing yin principle in treating patients of recurrent aphthae].

OBJECTIVE: To observe the therapeutic effect of Kouchuangping granule (KCP) on recurrent aphthae and explore its mechanism. METHODS: One hundred and forty-eight patients treated with KCP were observed and compared with 49 patients treated with tripterygii multiglycoside tablet as control in controlling relapse, prolonging intermittent period, improving local symptom and the influence on humoral and cellular immunity. In animal experiment, the effects of KCP on immunologic function, anti-exudation, anti-inflammation and analgesia were studied. RESULTS: The clinical markedly effective and cure rate of the KCP group was 62.8% and the total effective rate was 89.9%, which were significantly higher than those of the control group (40.8% and 75.5%, P < 0.01, P < 0.05). In the KCP group, the intermittent period of aphthous ulcer recurrence was prolonged to 6 months and the local symptoms were markedly improved, the differences were significant as compared with those before treatment and those in the control group (P < 0.01 or 0.05). The KCP showed effects in suppressing humoral immunity and enhancing cellular immunity. Results of experimental study showed that KCP could inhibit the supernormal reaction of cellular immunity to prevent and treat the hypersensitivity caused erosion and ulceration of mucosae, inhibit capillary permeability and WBC migration and abate the 5-hydroxytryptamine (5-HT) and histamine induced local swelling and pain. CONCLUSION: KCP has a significant effect in treating recurrent aphthae, the mechanism might be related with its effect on immunoregulation, anti-inflammation and anti-exudation.

Adult↗

[Craniovertebral decompression and posterior fossa reconstruction treatment of Chiari syringomyelia complex].

OBJECTIVE: To study the results of Chiari malformation/syringomyelia (CM-SM) complex treated by craniovertebral decompression and posterior fossa reconstruction (PFR). METHODS: 37 patients of CM-SM complex were treated surgically from 1994 to 1999. All patients underwent craniovertebral decompression and posterior fossa reconstruction. The procedure consisted of suboccipital craniectomy and laminectomy of C1 (when necessary C2), exploration and plugging of the obex, and resection of arachnoid adherence. A wide dural graft was used to reconstruct the cisterna magna artificially. Syrinx shunt was not performed. RESULTS: Follow-up for 0.5 to 4.5 years showed that 31 patients (83.8%) had their symptoms improved, 5 (13.5%) stabilized, but 1 (2.7%) deteriorated. Magnetic resonance was used to evaluate the morphological results. The shrinkage of the syrinx, upward migration of the hindbrain, the formation of an artificial cisterna magna were observed. CONCLUSIONS: Craniovertebral decompression and posterior fossa reconstruction in restoring the craniovertebral junction are recommended in the treatment of CM-SM complex.

Adolescent↗

[Multiple organ dysfunction syndrome after open chest wound and seawater immersion: experimental study].

OBJECTIVE: To evaluate the effect of seawater immersion on multiple organ dysfunction syndrome (MODS) after chest trauma. METHODS: Twenty health dogs were divided into two groups. Right open pneumothorax was induced in both control group (n = 10) and experimental group (n = 10). After induction of chest trauma, animals in the experimental group were immersed in artificial seawater. Blood samples were taken at seven different intervals for assessing blood gas, plasma level of TNFalpha, and IL-1 beta. Changes of serum alanine aminotransferase (ALT), aspartate amino-transferase (AST), creatine kinase (CK) lactate dehydrogenase (LDH) and creatinine (Cr) were measured. At the end of study, lung was harvested for assessing lung water content and ratio of wet weight and dry weight. RESULTS: A significant elevation of ALT, AST, CK and LDH was observed in both groups. Organ functional parameters in the experimental group were consistent with the failure standard at 30 minutes after seawater immersion, and those in the control group at 4 hours. Post-trauma mortality and incidence of MODS were much higher in the experimental group than those in the control group (P < 0.01). The plasma levels of TNFalpha and IL-1 beta significantly increased at 30 minutes and reached the highest level at 60 minutes after seawater immersion. The time of peak level appeared earlier in the experimental group than that in the control group. CONCLUSION: Seawater immersion after open chest trauma results in high incidence of MODS and high mortality rate due to progressive dysfunction of multiple organs.

Animals↗

[The effect of V-shaped nitinol alloy implantation on acetabular dysplasia: an experimental study].

OBJECTIVE: To observe the effect of V-shaped nitinol alloy implantation into the acetabular roof of puppies with acetabular dysplasia on acetabular dysplasia. METHODS: The puppies with acetabular dysplasia were divided randomly into two groups. Osteotomy was begun about 0.5 cm above the acetabulum, using a curved osteotome this cut must proceed between the medial wall of the ilium and medial wall of the acetabulum. The osteotomy does not have to be carried to the triradiate cartilage. When the osteotomy is completed, the superior aspect of the acetabulum can be hinged downward by curved osteotome. The V-shaped nitinol alloy was wedged securely in the osteotomy site. Roentgenogram was made 4 and 12 weeks after operation in all animals. RESULTS: The inclination of the acetabular roof was redirected and the acetabular index was decreased. Microscopic study showed a marked proliferation of cartilaginous cells of the acetabular cartilage. CONCLUSION: The V-shaped nitinol alloy implantation into the acetabular roof can correct the sloping acetabular roof, increase the coverage on the femoral head, and improve the growth of the acetabulum.

Acetabulum↗

[Establishment of rat submandibular gland squamous cell carcinoma induced by DMBA].

OBJECTIVE: To study carcinogenesis and development of salivary gland tumor and establish an animal model of submandibular gland (SMG) tumor. METHODS: Histopathological study during carcinogenesis in rat SMGs using (9,10-dimethyl-1,2-benzanthracene (DMBA) was evaluated. A total of 50 male and female Sprague-Dawley (SD) rats of 8 weeks old and 180-200 g weight were obtained from the Animal Center of Henan Medical University. Under pentobarbital sodium anesthesia, the left SMGs were exposed by surgical procedure. A sponge pellet (1.0 mm x 1.0 mm x 1.0 mm, made by authors) was used as the carrier of the carcinogen. The sponge containing 2% DMBA (Fluka, Switzerland)/acetone solution was implanted into the glandular tissue of the left SMGs. Four rats (2 males and 2 females) were killed after every 2 weeks of the DMBA/sponge implantation. The same method of sponge implantation without DMBA was used at the right side of SMG as a control. All rats left were killed after 20 weeks. The SMGs were fixed in 10% formalin buffer solution for 24 hours, and embedded in paraffin, then 4 microns-thick sections were made for histopathological study. RESULTS: The earliest tumor occurred after 4 weeks of implantation of sponge, a total of 21 lateral tumors were induced (10 females, 11 males). There was no tumor found in the controlled SMG. The peak time of tumor genesis was after 8-12 weeks of implantation, all tumors induced were squamous cell carcinomas(SCCs). The induced tumors grew slowly below the mandibles of rats, which were present as nodular masses without capsules, and the borders were not clear. They were slightly hard when palpated. The process of carcinogenesis can be described as following: squamous metaplasia of cyst-like structures occurred, then SCCs were induced and invaded surrounding tissues. No metastasis was observed in regional lymph nodes and other organs. CONCLUSION: SCCs of SMG can be induced by implantation of DMBA. The present study supports the conclusion that all duct segments undergo squamous metaplasia, and therefore may participate in the genesis of neoplasia during experimental carcinogenesis.

9,10-Dimethyl-1,2-benzanthracene↗

[Study on the plasmid instability of Bdellovibrio BDG-9].

A new method system was established in this paper to study the plasmid in stability of Bdellovibrio BDG-9. Using this system, it was found that when BDG-9 was cultured singly on the SMB plate, plasmid pST I was unstable although pST I still replicated and distributed to progeny cell normally. The results showed that the pST I copy number in single cell of BDG-9 decreased gradually to zero with the propagation of BDG-9. Additionally, plasmid pST I was very important for the growth of BDG-9, and with the lacking of pST I s, the growth and propagation of BDG-9 ceased.

Bdellovibrio↗

[Protective effect of total paeony glycoside against cerebral ischemia-reperfusion injury in mice].

OBJECTIVE: To investigate actions of Total Paeony Glycoside (TPG) on cerebral ischemia-reperfusion model in mice. METHODS: The cerebral ischemia-reperfusion models induced by lagation of bilateral common carotid arteries incompletely were used. RESULTS: It was found that TPG could improve the learning and memory capacity of model mice in step down test. TPG significantly reduced the decrease of superoxide dismutase(SOD), inhibited the increase of nitric oxide(NO) and lessened the level of malondialdehyde(MDA) in model mice. 75 mg.kg-1 TPG also reduced the decrease of lactate dehydrogenase (LDH) in cerebrum remarkedly. CONCLUSION: It is suggested that TPG possess obvious protective effects against cerebral ischemia-reperfusion mice.

Animals↗

Role of APC in the selection of immunodominant T cell epitopes.

Following antigenic challenge, MHC-restricted T cell responses are directed against a few dominant antigenic epitopes. Here, evidence is provided demonstrating the importance of APC in modulating the hierarchy of MHC class II-restricted T cell responses. Biochemical analysis of class II:peptide complexes in B cells revealed the presentation of a hierarchy of peptides derived from the Ig self Ag. Functional studies of kappa peptide:class II complexes from these cells indicated that nearly 20-fold more of an immunodominant epitope derived from kappa L chains was bound to class II DR4 compared with a subdominant epitope from this same Ag. In vivo, T cell responses were preferentially directed against the dominant kappa epitope as shown using Ig-primed DR4 transgenic mice. The bias in kappa epitope presentation was not linked to differences in class II:kappa peptide-binding affinity or epitope editing by HLA-DM. Rather, changes in native Ag structure were found to disrupt presentation of the immunodominant but not the subdominant kappa epitope; Ag refolding restored kappa epitope presentation. Thus, Ag tertiary conformation along with processing reactions within APC contribute to the selective presentation of a hierarchy of epitopes by MHC class II molecules.

Amino Acid Sequence↗

Correlation of the structural and functional domains in the membrane protein Vpu from HIV-1.

Vpu is an 81-residue membrane protein encoded by the HIV-1 genome. NMR experiments show that the protein folds into two distinct domains, a transmembrane hydrophobic helix and a cytoplasmic domain with two in-plane amphipathic alpha-helices separated by a linker region. Resonances in one-dimensional solid-state NMR spectra of uniformly (15)N labeled Vpu are clearly segregated into two bands at chemical shift frequencies associated with NH bonds in a transmembrane alpha-helix, perpendicular to the membrane surface, and with NH bonds in the cytoplasmic helices parallel to the membrane surface. Solid-state NMR spectra of truncated Vpu(2-51) (residues 2-51), which contains the transmembrane alpha-helix and the first amphipathic helix of the cytoplasmic domain, and of a construct Vpu(28-81) (residues 28-81), which contains only the cytoplasmic domain, support this structural model of Vpu in the membrane. Full-length Vpu (residues 2-81) forms discrete ion-conducting channels of heterogeneous conductance in lipid bilayers. The most frequent conductances were 22 +/- 3 pS and 12 +/- 3 pS in 0.5 M KCl and 29 +/- 3 pS and 12 +/- 3 pS in 0.5 M NaCl. In agreement with the structural model, truncated Vpu(2-51), which has the transmembrane helix, forms discrete channels in lipid bilayers, whereas the cytoplasmic domain Vpu(28-81), which lacks the transmembrane helix, does not. This finding shows that the channel activity is associated with the transmembrane helical domain. The pattern of channel activity is characteristic of the self-assembly of conductive oligomers in the membrane and is compatible with the structural and functional findings.

Amino Acid Sequence↗

A cytosolic catalase is needed to extend adult lifespan in C. elegans daf-C and clk-1 mutants.

The dauer larva is an alternative larval stage in Caenorhabditis elegans which allows animals to survive through periods of low food availability. Well-fed worms live for about three weeks, but dauer larvae can live for at least two months without affecting post-dauer lifespan. Mutations in daf-2 and age-1, which produce a dauer constitutive (Daf-C) phenotype, and in clk-1, which are believed to slow metabolism, markedly increase adult lifespan. Here we show that a ctl-1 mutation reduces adult lifespan in otherwise wild-type animals and eliminates the daf-c and clk-1-mediated extension of adult lifespan. ctl-1 encodes an unusual cytosolic catalase; a second gene, ctl-2, encodes a peroxisomal catalase. ctl-1 messenger RNA is increased in dauer larvae and adults with the daf-c mutations. We suggest that the ctl-1 catalase is needed during periods of starvation, as in the dauer larva, and that its misexpression in daf-c and clk-1 adults extends lifespan. Cytosolic catalase may have evolved to protect nematodes from oxidative damage produced during prolonged dormancy before reproductive maturity, or it may represent a general mechanism for permitting organisms to cope with the metabolic changes that accompany starvation.

Animals↗

Near-Infrared Laser Spectroscopy of the C(3)Delta-X(3)Delta Transition of TiS.

The (0, 0), (1, 0), (2, 0), (3, 0), and (4, 0) bands of the C(3)Delta-X(3)Delta transition of TiS, between 743-863 nm, were studied using the technique of laser vaporization/reaction with supersonic cooling and laser-induced fluorescence (LIF) spectroscopy. The linewidth of the LIF spectrum obtained was about 250 MHz. The P, Q, and R branches of each DeltaOmega = 0 subband were observed. A merged least-squares fit of the measured line positions yielded molecular parameters of the v = 0-4 levels of the C(3)Delta state and the v = 0 level of the X(3)Delta state. Copyright 1999 Academic Press.

Journal Article↗

Coexistence of immune-neuro-endocrine substances in the rat central neurons.

To investigate the expression of interleukin-2 (IL-2), metabotropic glutamate receptor subunit 1 (mGluR1) and estrogen receptor (ER) in neurons of the rat central nervous system (CNS) and identify the coexistence possibility of these immune-neuro-endocrine substances in the central neurons, the tri-labeling immunocytochemical technique with different species-specific primary antibodies (goat anti-IL-2 antibody, rabbit anti-mGluR1 antibody and mouse anti-ER antibody) were used to incubate two serial neighbor sections (one for demonstrating IL-2, another for mGluR1 and ER) of the cerebral cortex, medulla oblongata and spinal cord. There were IL-2-, mGluR1- and ER-immunoreactivity (IR)-positive labeled neurons in the above-mentioned central areas. The IL-2-IR production showed brown color, located in the cytoplasm; In the neighbor serial section, the mGluR1-IR, production showed blue-black color, located on the cell membrane; the ER-IR production also showed brown color, located in the cytoplasm and nuclei. There were mGluR1/ER double-labeled cells in the same section, which accounted for about 50%-60% of the total single and double labeled neurons. It was identified by projection check of serial neighbor sections that had mGluR1/ER/IL-2 tri-labeled cells, which accounted for about 30% of total mGluR1/ER double-labeled neurons. The results indicate that mGluR1, ER and Il-2 can coexist in the same rat central neurons, therefore, providing morphological basis for the theory about immune-neuro-endocrine network at the cellular level for the first time.

Animals↗

Heterologous expression of wild type and deglycosylated human sex steroid-binding protein (SBP or SHBG) in the yeast, Pichia pastoris. Characterization of the recombinant proteins.

Wild type, partially and fully-deglycosylated human sex steroid-binding protein (SBP or SHBG) cDNAs lacking the native cucaryotic signal sequence were cloned into a yeast expression vector containing the Saccharomyces cerevisiae alpha-factor for extracellular secretion. Following transformation into Pichia pastoris, the wild type and all constructed mutants were successfully expressed. The levels were lower for the deglycosylated mutants indicating that oligosaccharide side chains may play a role in SBP secretion. Under fermentation conditions, the wild type protein was expressed at a level of 4 mg/l while the fully-deglycosylated mutant T7A/N351Q/N367Q was expressed at about 1.5 mg/l. The latter was purified from several fermentation runs and was found to be completely deglycosylated, electrophoretically homogeneous and fully active. The aminoterminus was found to have the sequence NH2QSAHDPPAV- indicating that cleavage of the alpha-factor occurred at the A(+7)-Q(+8) peptide bond. The molecular mass of the subunit was determined to be 39,717.8 Da, which is in complete agreement with the amino acid sequence of the T7A/N351Q/N367/Q mutant. The equilibrium constants for the dissociation of 5alpha-dihydrotestosterone and steroid binding specificity were found to be identical to that of the human plasma protein indicating that the missing N-terminal segment NH2-LRPVLPT and the removal of oligosaccharide side chains do not affect the stability and active conformation of the protein. In conclusion, the data presented reveal that the SBP mutant T7A/N351Q/N367/Q is the protein of choice for solving the three-dimensional structure.

Amino Acid Sequence↗