Biomedical subjects

L Ma

Publications and source records attributed to L Ma.

At least 235 records · Page 13Linked to original sources

PubMed1999

[Observation on micronuclei incidence of peripheral blood lymphocyte in attendants diesel locomotive and wheel axle workers].

The analyses of micronuclei of peripheral blood lymphocyte was performed in 51 attendents in diesel locomotive and 30 wheel axle workers. The results showed that the rates of positive micronucleus, micronucleus cells and micronuclei in the attendants and the wheel axle workers were much higher than the control group. The frequencies of micronucleus cells and micronuclei obviously increased with the service time. The possible reasons which caused the micronucleus increase in two types of workers were discussed.

Adult↗

PubMed1999

Hoxa-10 deficient male mice exhibit abnormal development of the accessory sex organs.

The role of mammalian Hox genes in regulating segmental patterning of axial structures and the limb is well established. A similar role in development of soft tissue organ systems has recently been suggested by observations linking several 5' members of the HoxA and HoxD clusters to segmentation events and morphogenesis in the gastrointestinal and genitourinary systems. We have specifically examined the role of Hoxa-10 in development of the male accessory sex organs by characterizing expression of Hoxa-10 in the developing male reproductive tract and correlating expression to morphologic abnormalities in knockout mice deficient for Hoxa-10 function. We report that Hoxa-10 expression in the Wolffian duct and urogenital sinus is regionally restricted and temporally regulated. The domain of expression is defined anteriorly by the caudal epididymis and extends posteriorly to the prostatic anlagen of the urogenital sinus. Expression was maximal at E18 and down-regulated postnatally, well before accessory sex organ morphogenesis is completed. Expression in the prostatic anlagen of the urogenital sinus cultured in vitro does not depend upon the presence of testosterone. Loss of Hoxa-10 function is associated with diminished stromal clefting of the seminal vesicles and decreased size and branching of the coagulating gland. The ductal architecture of the coagulating gland was altered in approximately 30% of mutants examined and suggests a partial posterior morphologic transformation of the coagulating gland. We interpret these data to indicate that Hoxa-10 is expressed in a region specific manner during late gestation and into the perinatal period and that Hoxa-10 is required for normal accessory sex organ development.

Animals↗

PubMed1999

Electrospray ionization multiple-stage tandem mass spectrometric analysis of diglycosyldiacylglycerol glycolipids from the bacteria Bacillus pumilus.

Electrospray ionization (ESI) combined with multiple-stage tandem mass spectrometry (MS(n)) was used to directly analyze the glycolipid mixture from bacteria Bacillus pumilus without preliminary separation. Full scan ESI-MS revealed the composition of picomole quantities of glycerolglycolipid species containing C(14)-C(19) fatty acids, some of which were monounsaturated. Two main components were identified from their molecular masses and fragmentation pathways. The fragmentation pathway of the known compound compared with the investigated compound verified the proposed structure as 1(3)-acyl-2-pentadecanoyl-3(1)-O-[beta-D-glucopyranosyl-(1-->6)-O-beta-D-glucopyranosyl]-sn-glycerols. A comparison of the multiple tandem mass spectra of the different alkali-metal cation adducts indicates that the intensity of fragments and the dissociation pathways are dependent on the alkali-metal type. The basic structures of glycerolglycolipids were reflected clearly from the fragmentation patterns of the sodium cations. The intense fragments of the sugar residue from the precursor ions were obtained from the lithiated adduct ions. ESI-MS(n) spectra of [M + K](+) ions did not provide as much fragmentation as [M + Na](+) and [M + Li](+) adducts, but their spectra allow the position of glycerol acylation to be determined. On the basis of MS(2) spectra of [M + K](+) ions, it was established that all components have a C(15:0) fatty acid at the sn-2 position of the glycerol backbone and C(14)-C(19) acids at the sn-1 position of the glycerol backbone. Copyright 1999 John Wiley & Sons, Ltd.

Journal Article↗

PubMed1999

Capillary electrophoresis enantioseparation of drugs using beta-cyclodextrin polymer: intramolecular synergistic effect.

Enantiomers of eight basic compounds of pharmaceutical interest were studied by capillary electrophoresis (CE) using a soluble cyclodextrin (CD) polymer and native CD as chiral selectors. The effects of the polymer concentration and the pH of the buffer solution on resolution were examined. It was found that the beta-CD polymer shows higher stereoselectivity than its parent cyclodextrin. Such improvement is due to the structural difference between beta-CD and beta-CD polymer. These results suggested the existence of an intramolecular synergistic effect in CE.

Buffers↗

PubMed1999

Suppression of carrageenan-induced inflammation in vivo by an extract of the Chinese herbal remedy Tripterygium wilfordii Hook F.

OBJECTIVE AND DESIGN: The current studies investigated the effect of subacute administration of an ethyl acetate extract of the Chinese herbal remedy, Tripterygium wilfordii Hook F (TWHF) on the inflammatory response induced by carrageenan in the rat. MATERIALS AND SUBJECTS: F344 rats were randomly divided into 3 groups of seven animals. TREATMENT: The rats were treated orally for 5 days with either vehicle or an ethyl acetate extract of TWHF at a dose of 270 mg/kg, equivalent to 1/5 of the dose causing death in 50% of the animals. METHODS: Air pouches were induced subcutaneously on the backs of rats and injected with carrageenan on the last day of treatment. Sixteen hours after carrageenan challenge, the air pouches were removed and analyzed. Student's t-test was employed for statistical analysis. RESULTS: The number of exudate cells and the concentration of PGE2, nitrite and TNF-alpha in the exudate obtained from TWHF-treated animals were significantly reduced (by 69%, 78%, 57% and 77%, respectively) compared to that from vehicle-treated animals. mRNA for cyclooxygenase-2 was markedly suppressed in the air pouch lining tissue of TWHF treated rats (p < 0.001). In contrast, PGE2 content of the kidney and stomach and the production of PGE2, nitrite and TNF-alpha by spleen cells was not affected by treatment with TWHF. CONCLUSIONS: These results indicate that TWHF exerts a significant anti-inflammatory activity in vivo.

Acetates↗

PubMed1999

Antihypertensive drug therapy and antioxidant enzyme mRNA levels in spontaneously hypertensive (SHR) rats.

Previous studies have shown that chronic treatment of SHR (spontaneously hypertensive) rats with the antihypertensive drugs captopril, hydralazine and terazosin results in changes in the specific activities of the antioxidant enzymes glutathione peroxidase, catalase and Cu/Zn superoxide dismutase in liver and myocardium. In order to determine if these changes were caused by alterations in the levels of the mRNAs for these enzymes, the tissue levels of the antioxidant enzyme mRNAs have been measured. In myocardium, all three drug treatments increased Cu/Zn superoxide dismutase mRNA but decreased glutathione peroxidase mRNA levels, and in liver, all three drugs changed glutathione peroxidase mRNA levels. In comparison to untreated SHR animals, the levels of all three mRNAs were altered in the myocardium, but not in the liver, of normotensive WKY rats. Comparisons of mRNA levels with tissue enzyme specific activities suggest that tissue antioxidant enzyme expression is, in most cases, regulated by antihypertensive drugs through transcriptional control mechanisms.

Animals↗

PubMed1999

Polynitroxylated hemoglobin-based oxygen carrier: inhibition of free radical-induced microcirculatory dysfunction.

Reactive oxygen species have been identified as key mediators of leukocyte/endothelial cell interaction under various pathological conditions and diseases such as ischemia/reperfusion injury, inflammation, and after exposure to cigarette smoke. Consequently, antioxidants have been shown to successfully prevent the sequelae of these conditions, ranging from tissue infarction to atherogenesis. In this study we investigated whether, via its established superoxide dismutase-like activity, a novel polynitroxyl hemoglobin-based oxygen carrier (PNH), could affect the stimulation of leukocyte rolling and adhesion to endothelial cells in response to cigarette smoke. Using the dorsal skin fold chamber model for intravital microscopic observation of leukocyte/endothelium and -/platelet interactions in hamsters, we could demonstrate that cigarette smoke exposure elicited in control animals the rolling and adhesion of leukocytes along the endothelium of postcapillary venules and also of arterioles, as well as the formation of leukocyte/platelet aggregates. In contrast to the hemoglobin based oxygen carrier (HBOC) alone, that showed no therapeutic benefit, PNH significantly inhibited these proadhesive processes secondary to cigarette smoke. Also, PNH significantly reduced the formation of leukocyte/platelet aggregates in the blood stream of the cigarette smoke-exposed animals. These effects are not due to changes in microhemodynamic conditions, because wall shear rates remained unchanged in all three groups of animals.

Animals↗

PubMed1999

Cyclic AMP induces functional presynaptic boutons in hippocampal CA3-CA1 neuronal cultures.

Long-term forms of synaptic plasticity that may underlie learning and memory have been suggested to depend on changes in the number of synapses between presynaptic and postsynaptic neurons. Here we have investigated a form of synaptic plasticity in cultures of hippocampal CA3 and CA1 neurons related to the late phase of long-term potentiation, which depends on cAMP and protein synthesis. Using the fluorescent dye FM 1-43 to label active presynaptic terminals, we find that a membrane permeable analog of cAMP enhances the number of active presynaptic terminals and that this effect requires protein synthesis.

Animals↗

PubMed1999

Mapping of hKCa3 to chromosome 1q21 and investigation of linkage of CAG repeat polymorphism to schizophrenia.

CAG trinucleotide polymorphisms in the neuronal small conductance calcium-activated potassium channel gene hKCa3 have been reported to be associated with schizophrenia. Attempts to confirm this finding have met with mixed results. We investigated hKCa3 CAG allele lengths in families from the National Institute of Mental Health (NIMH) Schizophrenia Genetics Initiative, by comparing transmission to discordant siblings and parental transmission to affected offspring. Overall, there was no convincing evidence that hKCa3 CAG lengths differ between schizophrenics and controls. We did, however, observe a trend (P = 0.063) toward over-representation of long (> or = 19) CAG repeats in the shorter of the two hKCa3 alleles in schizophrenics. There was no evidence of excessive parental transmission of long CAG repeat alleles to affected offspring. In addition, we re-mapped hKCa3 and found that it resides on chromosome 1q21, in a region which has been linked to familial hemiplegic migraine, but not to schizophrenia. These data provide no significant support for the association of hKCa3 with schizophrenia.

Alleles↗

PubMed1999

Cigarette smoke and its extract delays ulcer healing and reduces nitric oxide synthase activity and angiogenesis in rat stomach.

1. The purpose of the present study was to examine whether cigarette smoke and its extract could affect ulcer healing, angiogenesis and nitric oxide synthase (NOS) activity in the gastric mucosa. 2. Ulcerated rats were either exposed to cigarette smoke or given smoke extract once daily for 3 days. Rats were killed and stomachs were removed for the measurement of ulcer size, angiogenesis and NOS activity. 3. Angiogenesis and constitutive NOS activity were concomitantly and dose-dependently reduced by cigarette smoke or its extract. The same treatments also delayed ulcer healing. 4. These results indicate that cigarette smoke and its extract repress the processes of new blood vessel formation and NOS activity during tissue repair in the gastric mucosa. These could, in turn, retard the healing process in the gastric mucosa.

Animals↗

PubMed1999

Acute desensitization of nociceptin/orphanin FQ inhibition of voltage-gated calcium channels in freshly dissociated hippocampal neurons.

Nociceptin/orphanin FQ (N/OFQ), an endogenous ligand for opioid receptor-like receptor, has been shown to inhibit high-voltage-gated calcium channels (VGCCs) in acutely dissociated rat hippocampal pyramidal cells [Knoflach, F., Reinscheid, R.K., Civelli, O. & Kemp, J.A. (1996), J. Neurosci., 16, 6657]. In this study, it was further demonstrated that N/OFQ inhibition of calcium channel current was blocked by its specific antagonist PGN, [Phe1-psi(CH2-NH)-Gly2]nociceptin (1-13)-NH2, and the EC50 of the N/OFQ inhibition was approximately 10 nM, indicating that this effect was really mediated via the opioid receptor-like receptor. The N/OFQ inhibition of the calcium channel current was significantly reduced, as the maximal inhibition decreased from 36 to 23%, by 1-min pretreatment of freshly dissociated hippocampal neurons with the same peptide. The inhibition completely recovered from this acute desensitization in less than 20 min. The N/OFQ inhibition was also greatly attenuated by pretreatment of the neurons with the GABAB (gamma-aminobutyric acid) agonist baclofen while the baclofen inhibition of the calcium channel current was significantly reduced by N/OFQ pretreatment, revealing the agonist-induced desensitization was heterologous in nature. This desensitization was blocked by pretreating the neurons with the sodium channel blocker, tetrodotoxin (TTX), or by removing the extracellular calcium, which indicates the necessity of membrane depolarization and extracellular calcium influx in the process. Furthermore, pretreatment of the neurons with the protein kinase C (PKC) activator, phorbol 12-myristate 13-acetate (PMA), attenuated the N/OFQ inhibition of the calcium channel current whereas the cAMP-dependent kinase A activator, forskolin, showed no effect, suggesting the probable involvement of PKC in the N/OFQ-induced desensitization.

Animals↗

PubMed1999

Endogenous delta-opioid and ORL1 receptors couple to phosphorylation and activation of p38 MAPK in NG108-15 cells and this is regulated by protein kinase A and protein kinase C.

The p38 mitogen-activated protein kinase (MAPK) cascade transduces multiple extracellular signals from cell surface to nucleus and is employed in cellular responses to cellular stresses and apoptotic regulation. The involvement of the p38 MAPK cascade in opioid- and opioid receptor-like receptor-1 (ORL1) receptor-mediated signal transduction was examined in NG108-15 neuroblastoma x glioma hybrid cells. Stimulation of endogenous delta-opioid receptor (DOR) or ORL1 resulted in activation of p38 MAPK. It also induced the activation of extracellular signal-regulated kinases (ERKs), another member of the MAPK family, with slower kinetics. Activation of p38 MAPK was abolished by selective antagonists of DOR or ORL1, pretreatment with pertussis toxin, or SB203580, a specific inhibitor of p38 MAPK. Inhibition of p38 MAPK had no significant effect on opioid-induced ERK activation, indicating that p38 MAPK activity was not required for ERK activation, though its stimulation preceded ERK activation. Inhibition of protein kinase A (PKA) strongly diminished p38 activation mediated by DOR or ORL1 but had no significant effect on ERK activation, and protein kinase C (PKC) inhibitors potentiated stimulation of p38 while inhibiting activation of ERKs. Taken together, our results provide the first evidence for coupling of DOR and ORL1 to the p38 MAPK cascade and clearly demonstrate that receptor-mediated activation of p38 MAPK both involves PKA and is negatively regulated by PKC.

Animals↗

PubMed1999

Genetic control of uterine receptivity during implantation.

Implantation involves complex molecular interactions between implanting blastocysts and the hormonally primed uterus. Gene targeting allows the generation of mice lacking a specific gene or genes and has proved to be of considerable value when combined with classical physiology in understanding many biological questions, such as the process of implantation. In this article, we review genes that have been demonstrated by gene targeting in mice to be required in the uterus for implantation. In particular, we focus on a specific class of developmental control genes, the mammalian Hox genes, and their role in this process. Lastly, we attempt to synthesize current knowledge about the genetic control of implantation and to build a working genetic model for the implantation pathway.

Animals↗

PubMed1999

Expression of growth hormone and insulin-like growth factor in the immune system of children.

Our objective was to study the effect of the growth hormone--insulin-like growth factor axis on the development of the immune system in children. We used radio receptor analysis, dot blot, in situ hybridization, and immunohistochemical techniques to determine the expression and distribution of growth hormone and growth hormone receptors, insulin-like growth factors, receptors and binding proteins in the thymus, lymph nodes and peripheral blood lymphocytes of children and adults. Our results showed that almost all components of the growth hormone-insulin-like growth factor axis were expressed in immune organs and cells, but the levels of expression varied. Growth hormone, insulin-like growth factor I, and insulin-like growth factor-binding proteins 1-6 were produced by immune cells in autocrine or paracrine ways. The expression of growth hormone receptors on peripheral blood lymphocytes was to be age-related. The growth hormone-insulin-like growth factor axis may help regulate the development and function of the immune system in children.

Adolescent↗

PubMed1999

Acute in vivo effects of ACTH by exo utero microinjection on differentiation, steroidogenesis and proliferation of fetal mouse adrenocytes.

Mouse embryos on embryonic day (E)13 or 14 were treated with ACTH1-24 by exo utero microinjection and the adrenal was examined after 16 and 32 h. Light microscopic morphometry showed that the ACTH treatment increased cell size and decreased cell density of the adrenocortical cells. Bromodeoxyuridine-labeling index did not alter significantly after the ACTH treatment. By immunohistochemistry, both number of cells expressing 11beta-hydroxylase and the staining intensity increased in the ACTH-treated glands compared to controls whereas expression of aldosterone synthase was detectable in neither the treated nor control groups. Ultrastructurally, the adrenocytes of the inner cortical zone of the ACTH-treated glands were characterized by strikingly increased content of the smooth endoplasmic reticulum, increased mitochondria with more vesicular cristae, lipid droplets with a much higher electron density along with the distribution altered from that in controls. All of the significant differences between the ACTH-treated and control glands occurred at 16 h but not at the 32 h interval. The present results indicated that the mouse fetal adrenocytes are already sensitive to ACTH during early period (E13 and 14) of their functional differentiation. In vivo acute treatment of ACTH stimulates cell-size, increase of fetal adrenocytes but not proliferation, and may directly or indirectly regulate multiple steps of the steroidogenic process of the fetal mouse adrenal.

Adrenal Cortex↗

PubMed1999

Polynitroxyl alphaalpha-hemoglobin (PNH) inhibits peroxide and superoxide-mediated neutrophil adherence to human endothelial cells.

Experimental hemoglobin-based O2 carriers e.g. cross-linked alphaalpha-hemoglobin (alphaalpha-Hb), are under investigation as potential blood substitutes. However, some Hb-based products form strong oxidant species in vivo that may cause adverse clinical effects. We report the prototype of a new class of modified Hb-based O2 carrier, polynitroxylated alphaalpha-Hb (PNH), which has antioxidant activities that may reduce inflammatory effects mediated by oxidant formation. We compared the effects of alphaalpha-Hb and PNH on xanthine oxidase and H2O2-induced neutrophil-endothelial adhesion in vitro. Both peroxide (>0.1 mM), and superoxide/peroxide generated by xanthine oxidase (XO) (> 10 mU/ml) + 0.1 mM xanthine (X), increased endothelial-neutrophil adhesion. At 30 microM, alphaalpha-Hb significantly increased X/XO-mediated adhesion, while PNH inhibited peroxide or X/XO induced adhesion, with maximal inhibition at 10 microM PNH. These data indicate that PNH has antioxidant-anti-inflammatory properties that suggest its use as a potentially safer blood substitute in reperfusion injury, stroke, myocardial infarction and other forms of inflammation.

Anti-Inflammatory Agents, Non-Steroidal↗

PubMed1999

Pneumocystis carinii dihydropteroate synthase but not dihydrofolate reductase gene mutations correlate with prior trimethoprim-sulfamethoxazole or dapsone use.

Recent studies of the human Pneumocystis carinii dihydropteroate synthase (DHPS) gene suggest that P. carinii is developing resistance to sulfamethoxazole (SMX) and dapsone. To explore whether P. carinii is also developing resistance to trimethoprim (TMP), the human P. carinii dihydrofolate reductase (DHFR) gene was cloned, DHFR and DHPS genes in 37 P. carinii isolates from 35 patients were sequenced, and the relationship between TMP-SMX or dapsone use and gene mutations was analyzed. The DHFR gene sequences were identical in all isolates except 1 with a synonymous substitution. In contrast, the DHPS gene sequences showed mutations in 16 of the 37 isolates; prior sulfa/sulfone prophylaxis was associated with the presence of these mutations (P<.001). In addition to suggesting that there is less selective pressure on DHFR than on DHPS, this study reinforces the hypothesis that mutations in the DHPS gene are likely involved in the development of sulfa resistance in P. carinii.

Amino Acid Sequence↗

PubMed1999

Dosimetric verification of a commercial inverse treatment planning system.

A commercial three-dimensional (3D) inverse treatment planning system, Corvus (Nomos Corporation, Sewickley, PA), was recently made available. This paper reports our preliminary results and experience with commissioning this system for clinical implementation. This system uses a simulated annealing inverse planning algorithm to calculate intensity-modulated fields. The intensity-modulated fields are divided into beam profiles that can be delivered by means of a sequence of leaf settings by a multileaf collimator (MLC). The treatments are delivered using a computer-controlled MLC. To test the dose calculation algorithm used by the Corvus software, the dose distributions for single rectangularly shaped fields were compared with water phantom scan data. The dose distributions predicted to be delivered by multiple fields were measured using an ion chamber that could be positioned in a rotatable cylindrical water phantom. Integrated charge collected by the ion chamber was used to check the absolute dose of single- and multifield intensity modulated treatments at various spatial points. The measured and predicted doses were found to agree to within 4% at all measurement points. Another set of measurements used a cubic polystyrene phantom with radiographic film to record the radiation dose distribution. The films were calibrated and scanned to yield two-dimensional isodose distributions. Finally, a beam imaging system (BIS) was used to measure the intensity-modulated x-ray beam patterns in the beam's-eye view. The BIS-measured images were then compared with a theoretical calculation based on the MLC leaf sequence files to verify that the treatment would be executed accurately and without machine faults. Excellent correlation (correlation coefficients > or = 0.96) was found for all cases. Treatment plans generated using intensity-modulated beams appear to be suitable for treatment of irregularly shaped tumours adjacent to critical structures. The results indicated that the system has potential for clinical radiation treatment planning and delivery and may in the future reduce treatment complexity.

Algorithms↗