Biomedical subjects

J Ma

Publications and source records attributed to J Ma.

At least 379 records · Page 21Linked to original sources

PubMed1997

Functional calcium release channel formed by the carboxyl-terminal portion of ryanodine receptor.

The ryanodine receptor (RyR) is one of the key proteins involved in excitation-contraction (E-C) coupling in skeletal muscle, where it functions as a Ca2+ release channel in the sarcoplasmic reticulum (SR) membrane. RyR consists of a single polypeptide of approximately 560 kDa normally arranged in a homotetrameric structure, which contains a carboxyl (C)-terminal transmembrane domain and a large amino (N)-terminal cytoplasmic domain. To test whether the carboxyl-terminal portion of RyR is sufficient to form a Ca2+ release channel, we expressed the full-length (RyR-wt) and C-terminal (RyR-C, approximately 130 kDa) RyR proteins in a Chinese hamster ovary (CHO) cell line, and measured their Ca2+ release channel functions in planar lipid bilayer membranes. The single-channel properties of RyR-wt were found to be similar to those of RyR from skeletal muscle SR. The RyR-C protein forms a cation-selective channel that shares some of the channel properties with RyR-wt, including activation by cytoplasmic Ca2+ and regulation by ryanodine. Unlike RyR-wt, which exhibits a linear current-voltage relationship and inactivates at millimolar Ca2+, the channels formed by RyR-C display significant inward rectification and fail to close at high cytoplasmic Ca2+. Our results show that the C-terminal portion of RyR contains structures sufficient to form a functional Ca2+ release channel, but the N-terminal portion of RyR also affects the ion-conduction and calcium-dependent regulation of the Ca2+ release channel.

Animals↗

PubMed1997

Effective tumor vaccines generated by in vitro modification of tumor cells with cytokines and bispecific monoclonal antibodies.

Antitumor immune responses are mediated primarily by T cells. Downregulation of the major histocompatibility complex (MHC) and the molecules that costimulate the immune response is associated with defective signaling by tumor cells for T-cell activation. In vitro treatment with a combination of cytokines significantly increased the expression of MHC class I and adhesion molecules on tumor cell surfaces. When tumor cells were first incubated with a bispecific monoclonal antibody that binds antigen on tumor cells to CD28 on T cells, the modified tumor cells become immunogenic and are able to stimulate naive T cells, generating tumor-specific cytotoxic T cells in vitro. Immunization with the modified tumor cells elicits an immune response mediated by CD8+ T cells. This response protected against a challenge with parental tumor cells and cured established tumors. The approach was effective in both low immunogenic and nonimmunogenic tumor model systems. Modification of tumor cells with this two-step procedure may provide a strategy for development of tumor vaccines that is effective for cancer immunotherapy.

Animals↗

PubMed1997

Caffeine-induced release of intracellular Ca2+ from Chinese hamster ovary cells expressing skeletal muscle ryanodine receptor. Effects on full-length and carboxyl-terminal portion of Ca2+ release channels.

The ryanodine receptor (RyR)/Ca2+ release channel is an essential component of excitation-contraction coupling in striated muscle cells. To study the function and regulation of the Ca2+ release channel, we tested the effect of caffeine on the full-length and carboxyl-terminal portion of skeletal muscle RyR expressed in a Chinese hamster ovary (CHO) cell line. Caffeine induced openings of the full length RyR channels in a concentration-dependent manner, but it had no effect on the carboxyl-terminal RyR channels. CHO cells expressing the carboxyl-terminal RyR proteins displayed spontaneous changes of intracellular [Ca2+]. Unlike the native RyR channels in muscle cells, which display localized Ca2+ release events (i.e., "Ca2+ sparks" in cardiac muscle and "local release events" in skeletal muscle), CHO cells expressing the full length RyR proteins did not exhibit detectable spontaneous or caffeine-induced local Ca2+ release events. Our data suggest that the binding site for caffeine is likely to reside within the amino-terminal portion of RyR, and the localized Ca2+ release events observed in muscle cells may involve gating of a group of Ca2+ release channels and/or interaction of RyR with muscle-specific proteins.

Animals↗

PubMed1997

Relation of plasma phospholipid and cholesterol ester fatty acid composition to carotid artery intima-media thickness: the Atherosclerosis Risk in Communities (ARIC) Study.

We examined the relation of fatty acid composition of plasma phospholipids and cholesterol esters with carotid artery intima-media thickness (a measure of atherosclerosis) in 2872 white men and women aged 45-64 y from the Minneapolis center of the Atherosclerosis Risk in Communities Study. In both men and women, average carotid intima-media thickness was associated significantly (P < 0.01) and positively with saturated (SFA) and monounsaturated fatty acid composition, and inversely with polyunsaturated fatty acid (PUFA) composition and the ratio of PUFAs to SFAs in both phospholipids and cholesterol esters. These associations were independent of age, cigarette smoking, low-density-lipoprotein (LDL) cholesterol, high-density-lipoprotein (HDL) cholesterol, body mass index, diabetes, and hypertension in men; but in women, only SFAs and PUFAs in the cholesterol esters and the ratio of PUFAs to SFAs were independently associated. The plasma fatty acid pattern is associated with carotid atherosclerosis in a direction generally consistent with the dietary fat-coronary artery disease relation. These results support recommendations to reduce dietary saturated fat to prevent cardiovascular disease.

Arteriosclerosis↗

PubMed1997

Improved 32P-postlabelling assay for the quantification of the major platinum-DNA adducts.

For the improvement of chemotherapy with platinum (Pt)-containing drugs a sensitive assay to detect the induced Pt-DNA adducts is needed. Therefore, the 32P-postlabelling assay, described by Blommaert and Saris (Nucleic Acids Res., 1995, 23, 1300-1306), to detect the major adducts Pt-GG and Pt-AG has substantially been improved and compared with ELISA and AAS. For the quantification of the adducts, TpT was added as an internal standard immediately after isolation of the Pt-adducts from digested DNA samples. It was found that 32P-labelling of both GpG and ApG, the dinucleotides obtained after deplatination of the adducts, was equally efficient as that of TpT. To isolate the Pt-adducts on basis of a positive charge, the pH of DNA digests was adjusted to approximately 3 prior to separation by strong cation-exchange chromatography. For the subsequent deplatination a volume of only 12 microl of 0.2 M NaCN was used, which did not interfere with the following labelling step. The quantification of the 32P-labelled dinucleotides was performed by phosphorimaging of spots after separation on TLC as well as by 32P-counting of fractions collected after separation by HPLC. The method was used to determine adduct levels in in vitro cisplatin-treated DNA and in DNA isolated from cisplatin-treated cultured cells, tumor xenografts from cisplatin-treated mice, and from white blood cells and (tumor) tissues from cisplatin-treated patients. The results show a significant correlation with the adduct levels as determined with atomic absorption spectroscopy (high levels) or with specific antibodies (low levels). This assay appears to be useful for the determination of low levels of Pt-adducts in small DNA samples as present in clinical specimens such as blood and tumor tissue, but also in buccal mucosal cells and fine needle aspirates.

Animals↗

PubMed1997

Effect of brain irradiation on blood-CSF barrier permeability of chemotherapeutic agents.

Effect of irradiation on blood-cerebrospinal fluid (CSF) barrier (BCB) was studied quantitatively by observing the effect of methotrexate (MTX) permeation into the CSF before, during, and after brain irradiation after i.v. injection of MTX. Observation of 15 brain tumor patients indicated that in large brain tumors, the BCB was seriously damaged; in small tumors, the BCB would gradually open. Compared with the findings before irradiation, the increase of permeability of MTX was zero to threefold. It is thus advisable to give chemotherapy only after 20 Gy of irradiation.

Antimetabolites, Antineoplastic↗

PubMed1997

Isoflurane-induced cerebral hyperemia in neuronal nitric oxide synthase gene deficient mice.

BACKGROUND: Nitric oxide (NO) has been reported to play an important role in isoflurane-induced cerebral hyperemia in vivo. In the brain, there are two constitutive isoforms of NO synthase (NOS), endothelial NOS (eNOS), and neuronal NOS (nNOS). Recently, the mutant mouse deficient in nNOS gene expression (nNOS knockout) has been developed. The present study was designed to examine the role of the two constitutive NOS isoforms in cerebral blood flow (CBF) response to isoflurane using this nNOS knockout mouse. METHODS: Regional CBF (rCBF) in the cerebral cortex was measured with laser-Doppler flowmetry in wild-type mice (129/SV or C57BL/6) and nNOS knockout mice during stepwise increases in the inspired concentration of isoflurane from 0.6 vol% to 1.2, 1.8, and 2.4 vol%. Subsequently, a NOS inhibitor, N omega-nitro-L-arginine (L-NNA), was administered intravenously (20 mg/kg), and 45 min later, the rCBF response to isoflurane was tested again. In separate groups of wild-type mice and the knockout mice, the inactive enantiomer, N omega-nitro-D-arginine (D-NNA) was administered intravenously in place of L-NNA. Brain NOS activity was measured with radio-labeled L-arginine to L-citrulline conversion after treatment with L-NNA and D-NNA. RESULTS: Isoflurane produced dose-dependent increases in rCBF by 25 +/- 3%, 74 +/- 10%, and 108 +/- 14% (SEM) in 129/SV mice and by 32 +/- 2%, 71 +/- 3%, and 96 +/- 7% in C57BL/6 mice at 1.2, 1.8, and 2.4 vol%, respectively. These increases were attenuated at every anesthetic concentration by L-NNA but not by D-NNA. Brain NOS activity was decreased by 92 +/- 2% with L-NNA compared with D-NNA. In nNOS knockout mice, isoflurane increased rCBF by 67 +/- 8%, 88 +/- 12%, and 112 +/- 18% at 1.2, 1.8, and 2.4 vol%, respectively. The increase in rCBF at 1.2 vol% was significantly greater in the nNOS knockout mice than that in the wild-type mice. Administration of L-NNA in the knockout mice attenuated the rCBF response to isoflurane at 1.2 and 1.8 vol% but had no effect on the response at 2.4 vol%. CONCLUSIONS: In nNOS knockout mice, the cerebral hyperemic response to isoflurane is preserved by compensatory mechanism(s) that is NO-independent at 2.4 vol%, although it may involve eNOS at 1.2 and 1.8 vol%. It is suggested that in wild-type mice, eNOS and nNOS contribute to isoflurane-induced increase in rCBF. At lower concentrations (1.2 and 1.8 vol%), eNOS may be involved, whereas at 2.4 vol%, nNOS may be involved.

Anesthetics, Inhalation↗

PubMed1997

Influence of air flow on the behavior of thoron and its progeny in a traditional Japanese house.

Air flow influence on the spatial distribution of thoron (220Rn) concentration in a typical Japanese traditional house was investigated at various indoor air flow levels. The effect of air flow on the behavior of both thoron and radon progeny were examined simultaneously. Measurements were carried out by using two types of passive monitors, the radon-thoron discriminative monitor and the Radtrak monitor. Thoron and radon progeny were measured by filter grab sampling with ZnS scintillation counting. Under static condition, a horizontal distribution with greatly varied thoron concentrations was found as reported by previous studies. Under turbulent conditions, thoron concentrations in the middle of the room increased and the concentration gradient of thoron gas became lower. An obvious vertical distribution of thoron was also observed. Prominent diurnal variation of radon progeny concentrations was observed whereas that of thoron progeny concentrations was not. Concentration of thoron progeny changed little at different air flow levels, although the thoron gas level at the middle of the room varied significantly. The influence of air flows on detection efficiencies of the two types of thoron monitors were also checked. The mechanism of behavioral change of thoron and its progeny in turbulent atmosphere is discussed.

Air Movements↗

PubMed1997

Characterization of short tandem repeats from thirty-one human telomeres.

Completion of genetic and physical maps requires markers from the ends (telomeres) of every human chromosome. We have searched for short tandem repeats (microsatellites) in cosmid and P1 clones and generated 661 sequence-tagged sites (STS) from the terminal 300 kb of 31 human chromosome ends. PCR assays were successfully designed for 58 microsatellites and mapped both genetically and on radiation hybrids (RHs) to confirm their telomeric location. Sequence analysis revealed marked variation in sequence composition, consistent with the hypothesis that even very highly GC-rich chromosome bands (the T bands) are not homogenous. The STSs that we have generated will be a necessary resource for the construction of physical maps of these complex regions of the genome.

Base Sequence↗

PubMed1997

CYP2J subfamily cytochrome P450s in the gastrointestinal tract: expression, localization, and potential functional significance.

Our laboratory recently described a new human cytochrome P450 arachidonic acid epoxygenase (CYP2J2) and the corresponding rat homologue (CYP2J3), both of which were expressed in extrahepatic tissues. Northern analysis of RNA prepared from the human and rat intestine demonstrated that CYP2J2 and CYP2J3 mRNAs were expressed primarily in the small intestine and colon. In contrast, immunoblotting studies using a polyclonal antibody raised against recombinant CYP2J2 showed that CYP2J proteins were expressed throughout the gastrointestinal tract. Immunohistochemical staining of formalin-fixed, paraffin-embedded intestinal sections using anti-CYP2J2 IgG and avidin-biotin-peroxidase detection revealed that CYP2J proteins were present at high levels in nerve cells of autonomic ganglia, epithelial cells, intestinal smooth muscle cells, and vascular endothelium. The distribution of this immunoreactivity was confirmed by in situ hybridization using a CYP2J2-specific antisense RNA probe. Microsomal fractions prepared from human jejunum catalyzed the NADPH-dependent metabolism of arachidonic acid to epoxyeicosatrienoic acids as the principal reaction products. Direct evidence for the in vivo epoxidation of arachidonic acid by intestinal cytochrome P450 was provided by documenting, for the first time, the presence of epoxyeicosatrienoic acids in human jejunum by gas chromatography/mass spectrometry. We conclude that human and rat intestine contain an arachidonic acid epoxygenase belonging to the CYP2J subfamily that is localized to autonomic ganglion cells, epithelial cells, smooth muscle cells, and vascular endothelium. In addition to the known effects on intestinal vascular tone, we speculate that CYP2J products may be involved in the release of intestinal neuropeptides, control of intestinal motility, and/or modulation of intestinal fluid/electrolyte transport.

8,11,14-Eicosatrienoic Acid↗

PubMed1997

Characterization of a neuregulin-related gene, Don-1, that is highly expressed in restricted regions of the cerebellum and hippocampus.

Members of the epidermal growth factor family of receptors have long been implicated in the pathogenesis of various tumors, and more recently, apparent roles in the developing heart and nervous system have been described. Numerous ligands that activate these receptors have been isolated. We report here on the cloning and initial characterization of a second ligand for the erbB family of receptors. This factor, which we have termed Don-1 (divergent of neuregulin 1), has structural similarity with the neuregulins. We have isolated four splice variants, two each from human and mouse, and have shown that they are capable of inducing tyrosine phosphorylation of erbB3, erbB4, and erbB2. In contrast to those of neuregulin, high levels of expression of Don-1 are restricted to the cerebellum and dentate gyrus in the adult brain and to fetal tissues.

Amino Acid Sequence↗

PubMed1997

Correlation of glioma cell regression with inhibition of insulin-like growth factor 1 and insulin-like growth factor-binding protein-2 expression.

To explore the antitumor effect of insulin-like growth factor 1 (IGF-I) antisense RNA and the interaction of IGF-I with insulin-like growth factor-binding proteins (IGFBPs) in glioma cells, a recombinant retrovirus expressing IGF-I antisense RNA was constructed and introduced into C6 glioma cells. IGF-I antisense RNA reverses the transformed phenotype in glioma cells and inhibits glioma cell growth by blocking overexpression of endogenous IGF-I. Expression of IGFBP-2 is increased in glioma cells as compared with normal adult glial cells. IGF-I antisense RNA also inhibits expression of IGFBP-2 in glioma cells, but does not influence expression of the other IGFBPs. Although IGFBP-2 in conditioned medium from wild-type C6 cell cultures itself does not directly influence glioma cell growth, it synergistically enhances exogenous IGF-I-mediated DNA synthesis in IGF-I-negative C6 cells. These findings indicate the inhibitory effect of IGF-I antisense RNA on growth and development of glioma cells. IGF-I-dependent glioma cell growth may, in some circumstances, require IGFBP-2 as a cofactor. The antitumor effect of IGF-I antisense RNA is also associated with inhibition of IGFBP-2 expression.

Animals↗

PubMed1997

Phase I and pharmacologic study of docetaxel and cisplatin in patients with advanced solid tumors.

PURPOSE: This phase I study was performed to assess the feasibility of the combination of docetaxel and cisplatin and to determine the maximum-tolerated dose (MTD) and the side effects with an emphasis on sequence-dependent side effects. MATERIALS AND METHODS: Patients who were not pretreated with taxanes or cisplatin derivatives and who had received no more than one prior combination chemotherapy regimen or two single-agent regimens were entered. Treatment consisted of docetaxel given as a 1-hour infusion followed by cisplatin as a 3-hour infusion (schedule A), or cisplatin followed by docetaxel (schedule B). Docetaxel doses ranged from 55 to 100 mg/m2 and cisplatin doses from 50 to 100 mg/m2. RESULTS: Leukocytopenia and granulocytopenia were common (overall, 90%; grade 3 or 4, 87%), short-lasting, and docetaxel dose-dependent. Infections and neutropenic fever occurred in 10% and 4.5% of courses, respectively. Nonhematologic toxicities were mild to moderate and included alopecia, nausea, vomiting, diarrhea, mucositis, neurotoxicity, fluid retention, and skin and nail toxicity. There were no significant differences in pharmacokinetic parameters between schedules A and B. Tumor responses included one complete response (CR) and nine partial responses (PRs). CONCLUSION: The dose levels docetaxel 100 mg/m2 plus cisplatin 75 mg/m2 and docetaxel 85 mg/m2 plus cisplatin 100 mg/m2 appeared to be manageable. At these dose levels, the median relative dose-intensity was high and 81% and 88% of all cycles, respectively, could be given at full dose. Schedule A is advocated for further treatment.

Adult↗

PubMed1997

[Effects of permissive hypercapnia on cardiopulmonary function in acute lung injury model].

OBJECTIVE: To observe the effects of permissive hypercapnia on cardiopulmonary function in oleic acid induced acute lung injury (ALI) models. METHOD: ALI models of pigs were induced successfully by infusing oleic acid, Swan-Ganz cathether was used for monitoring hemodynamics and different low tidal volumes were set for variable hypercapnia. RESULTS: ALI was characterized by an increase in airway pressure and a decrease in static compliance (Cst), artery oxygen tension (PaO2), oxygenation index and cardiac output. There was also an increase in mean pulmonary artery pressure (mPAP), pulmonary vascular resistance (PVR), systemic vascular resistance (SVR) and shunt fraction. After using 0.98 kPa (1 kPa = 10.2 cmH2O) PEEP, some of cardiopulmonary functions were improved. While reduced tidal volume to 7.7 +/- 0.3 ml/kg and PaCO2 increased to 9.44 +/- 1.27 kPa (1 kPa = 7.5 mmHg), which caused neither a change in PaO2/FiO2, PaO2, Cst nor in SVR, PVR but an increase in cardiac output. Though ventilation setting did not change except for the reducing tidal volume to 6.1 +/- 0.6 ml/kg and PaCO2 reached 12.1 +/- 1.05 kPa, then various adverse effects on cardiopulmonary system were observed. CONCLUSION: It seems that mechanical ventilation with permissive hypercapnia was safe at certain level.

Animals↗

PubMed1997

[Interactions between selenium and cadmium on lipid peroxidation of encephalon in mice].

70 Kunming male mice were randomly divided into five groups. Three groups were injected intraperitoneally with selenium (Se) on the dosages of 0.00, 0.05 and 0.10 mg/kg body weight and other two groups were treated with 0.23 mg/kg cadmium (Cd) and 0.10 mg/kg Se plus 0.23 mg/kg Cd, for 50 days. The concentrations of glutathione (GSH) and malonic dialdehyde (MDA) of cerebellum, pons, corpora quadrigemina, thalamus and pallium were detected respectively. The results showed that the GSH concentrations in these tissues decreased in all exposed groups. Cd increased the MDA level significantly in pons, corpora quadrigemina and thalamus, and Se could antagonize the harmful effect induced by Cd. But Se itself could also decrease the GSH level of encephalon.

Animals↗

PubMed1997

[Intelligence, memory and event-related potentials in patients with multiple sclerosis].

To learn the characteristics of cognitive disturbance of patients with multiple sclerosis (MS). We divided 55 patients with MS into two groups and 71 normal subjects were tested with the Wechsler Adult Intelligence Scale, Clinical Memory Scale and Eventrelated potentials (ERP). Disturbances of intelligence and memory occurred along the course of MS at various degrees. The memory quotient (MQ), full intelligence quotient (FIQ), verbal quotient (VIQ) and proce-ssing quotient (PIQ) of patients with the intelligence quotient (IQ) less than 80 scores were 76%, 32%, 24% and 70% respectively (P < 0.01). The scores of MQ, FIQ and VIQ in patients with MS of cerebral type or cerebro-spine type was lower than those of the spine type (P < 0.005). The score of patients with MS in active stage was less than that of MS in inactive stage (P < 0.001). The intelligence disturbances of MS patients were usually characterized by subcortical dementia and showed slight or moderate degree by DSM-III criteria. In patients of chronic active type, it may be characterized either by cortical dementia or subcortical dementia and showed moderate or severe degree. MS2 patient had significantly prolonged N2 and P300 latencies difference as well as low P300 amplitude compared with controls (P < 0.001). The disterbance of intelligence and memory with MS shows the important implication for the course of MS and the therapeutic effect as well as the prognosis.

Adult↗

PubMed1997

[OKT3 treatment of refractory renal allograft rejection].

Between January 1993 and June 1996, 44 episodes of refractory renal allograft rejection were treated with OKT3 to understand the curative effect of OKT3. Six of 7 accelerated and 31 of 37 acute rejection episodes were reversed. The reverse rate was 84.6%. Immediate response to OKT3 was in 25 and delayed response in 12 patients. The mean reverse time was 7 +/- 4 days in immediate response and 34 +/- 3 days in delayed response (P < 0.01). It was claimed that OKT3 had high effect in the treatment of refractory renal allograft rejection. Cytomegalovirus infection and cytokins release syndrome were the main side effect of treatment with OKT3. The delayed response would be associated with cytokins release syndrome and damage of rejection. Patients with lower titre of anti-OKT3 antibodies could be retreated with OKT3.

Adolescent↗

PubMed1997

[Detection of antineutrophil cytoplasmic antibodies for the values of Wegener's granulomatosis diagnosis and activity judgment].

OBJECTIVE: To investigate the clinical significance of antineutrophil cytoplasmic antibodies (ANCA) in Wegener's granulomatosis (WG) and other diseases. METHOD: Indirect immunofluorescence was applied to detect serum ANCA of 204 patients and 48 normal controls. Enzyme-linked immunosorbent assay (ELISA) was used to detect antimyeloperoxidase (MPO) antibodies. RESULTS: The frequency of ANCA in sera of WG patients was 75% and significantly higher than those in sera of other groups (P < 0.05). ELISA demonstrated that MPO was the major antigen recognized by perinuclear ANCA (P-ANCA). Cytoplasmic ANCA (C-ANCA) was always positive and high titers in sera of active WG patients, but turned to negative or low titers in remission. CONCLUSION: These results suggested that C-ANCA was specific for WG and was a marker for disease activity in WG. P-ANCA wasn't specific for WG, but related to vasculitis.

Antibodies, Antineutrophil Cytoplasmic↗