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Biomedical subjects

G Yu

Publications and source records attributed to G Yu.

At least 253 records · Page 14Linked to original sources
PubMed1992

Large granular lymphocyte proliferation with the natural killer-cell phenotype.

Lymphoproliferated disorders involving large granular lymphocytes (LGL) can be divided into a common T-cell subset (CD3+, CD8+) and a rarer natural killer (NK)-cell subset (CD2+, CD3-). The immunophenotype, clinical pathologic features, and cytogenetic and molecular genetic analyses are reported for seven patients with NK-cell-LGL proliferation. The typical immunophenotype was CD2+, CD3-, CD4-, CD11b+, and CD16+ or CD56+. A low but variable percentage of cells were CD8+ or CD57+. Unusual phenotypes with CD2- (1 of 7), CD11b- (1 of 7), or CD16-/CD56- (1 of 7) cells were seen. Strong NK-cell activity was observed in all cases, indicating that none of the NK-cell markers (CD11b, CD16, CD56, CD57) is essential for NK-cell activity. One patient died shortly after diagnosis from coexistent refractory multiple myeloma and another patient died within 1 month from the LGL proliferation. The other patients had been followed for 12 to 70 months, with a median follow-up period of 38 months. There was no progression of their LGL proliferation. Lymphocyte counts varied from 3.3 x 10(3)/microL to 58.4 x 10(3)/microL at the time of diagnosis. Unexplained anemia and neutropenia were observed in one patient. Cytogenetic abnormalities were detected in two of four patients studied with t(6;12) in one and der(5), der(6), and der(11) in the other. The approximately T gamma and T beta genes were in the germline configuration and Epstein-Barr virus DNA was undetectable in five of five patients studied. Natural killer-cell LGL proliferations were morphologically indistinguishable from T-cell LGL proliferations. However, the two were immunophenotypically and genotypically distinct and NK-cell activity was consistently observed in the former. Most of the NK-cell proliferations also were chronic indolent disorders and the incidence of associated cytopenias seemed to be lower than T-cell LGL proliferations.

Adult↗
PubMed1992

Cardiac A2 adenosine receptors--influence of ischaemia.

OBJECTIVE: The aim was to detect cardiac A2 adenosine receptors through radioligand binding, and to assess the effect of ischaemia on these receptors. METHODS: Isolated working rat hearts were subjected either to aerobic perfusion or to global ischaemia. A membrane fraction was prepared from ventricular tissue, and 3H-5'-N-ethylcarboxamide adenosine (NECA) binding was determined in the presence of N6-cyclopentyl adenosine (CPA). A2 binding was calculated as the fraction of NECA binding displaced by 100 microM CPA but not displaced by 50 nM CPA. RESULTS: Analysis of A2 NECA binding according to single binding site model yielded Kd = 22.0 nM, Bmax = 34.0 fmol.mg-1 in control hearts; Kd = 49.7 nM, Bmax = 44.3 fmol.mg-1 in hearts subjected to 30 min ischaemia (p < 0.05 for difference in Kd). In the control group a two site model provided a significantly (p < 0.05) better fit (Kd = 5.6 and 183.7 nM, Bmax = 9.5 and 64.4 fmol.mg-1 for the high and low affinity sites respectively). The high affinity component of A2 NECA binding disappeared in the presence of the GTP analogue guanyl-5'-yl imidodiphosphate, suggesting the existence of multiple coupling states of the receptor. In the ischaemic group no significant improvement in data fitting was obtained with the two site model. CONCLUSIONS: The results provide evidence of the existence of cardiac A2 adenosine receptors. Ischaemia modifies receptor properties and appears to affect chiefly the high affinity component of A2 binding, possibly by preventing receptor interaction with membrane G proteins.

Adenosine↗
PubMed1992

Identification of a human cDNA encoding a protein that is structurally and functionally related to the yeast adenylyl cyclase-associated CAP proteins.

The adenylyl cyclases of both Saccharomyces cerevisiae and Schizosaccharomyces pombe are associated with related proteins named CAP. In S. cerevisiae, CAP is required for cellular responses mediated by the RAS/cyclic AMP pathway. Both yeast CAPs appear to be bifunctional proteins: the N-terminal domains are required for the proper function of adenylyl cyclase, while loss of the C-terminal domains results in morphological and nutritional defects that appear to be unrelated to the cAMP pathways. Expression of either yeast CAP in the heterologous yeast suppresses phenotypes associated with loss of the C-terminal domain of the endogenous CAP but does not suppress loss of the N-terminal domain. On the basis of the homology between the two yeast CAP proteins, we have designed degenerate oligonucleotides that we used to detect, by the polymerase chain reaction method, a human cDNA fragment encoding a CAP-related peptide. Using the polymerase chain reaction fragment as a probe, we isolated a human cDNA clone encoding a 475-amino-acid protein that is homologous to the yeast CAP proteins. Expression of the human CAP protein in S. cerevisiae suppresses the phenotypes associated with loss of the C-terminal domain of CAP but does not suppress phenotypes associated with loss of the N-terminal domain. Thus, CAP proteins have been structurally and, to some extent, functionally conserved in evolution between yeasts and mammals.

Adaptor Proteins, Signal Transducing↗
PubMed1992

Effect of gallopamil on cardiac sarcoplasmic reticulum.

We investigated the effect of gallopamil on cardiac sarcoplasmic reticulum (SR) function. Heavy SR was prepared from bovine ventricular muscle. Oxalate-supported calcium uptake was stimulated by gallopamil at concentrations ranging from 10 to 300 nM, whereas higher concentrations were ineffective. Peak stimulation averaged 25-30% of control calcium uptake and was observed at free calcium concentrations ranging from 1 to 6 microM. Calcium uptake is actually the difference between active calcium transport by SR calcium-adenosine triphosphate (calcium-ATPase), and passive efflux through SR calcium-release channels. In the presence of 300 microM of ryanodine, a blocker of SR channels, calcium uptake increased by 43% under control conditions, but not further stimulation was produced by gallopamil. SR calcium-ATPase was not affected by gallopamil. Similar results were obtained when oxalate-supported calcium uptake was determined with use of unfractionated homogenate obtained from rat hearts. We conclude that gallopamil acts on SR calcium-release channels and reduces the probability of channel opening and/or channel conductivity. The dose-response curve is bell shaped, and the maximum effect, which corresponds to 65% of the maximum effect of ryanodine, is achieved at therapeutic concentrations. Such action might contribute to the beneficial effect of gallopamil in the treatment of myocardial ischemia.

Animals↗
PubMed1992

[Variations in the purine metabolism of the reperfused heart].

Isolated hearts were subjected to 30 min of aerobic perfusion followed by 10 min of global normothermic ischemia and 40 min of reperfusion. We determined the release of purine catabolites (adenosine, inosine, hypoxanthine, xanthine, uric acid) and the incorporation of exogenous 3H-adenosine and 14C-hypoxanthine into cellular nucleotides. Ischemia-reperfusion produced remarkable reduction in the release of purine catabolites, with no significant variation in the incorporation of adenosine and hypoxanthine.

Analysis of Variance↗
PubMed1992

Protection of isolated perfused working rat heart from oxidative stress by exogenous L-propionyl carnitine.

The effect of exogenous L-propionyl carnitine on peroxidative injury was investigated on isolated working rat hearts. The addition of 190 microM hydrogen peroxide to the perfusion buffer caused a marked decrease in aortic flow, minute work and peak aortic pressure, and a release of intracellular enzymes. In the presence of L-propionyl carnitine the haemodynamic damage was significantly lower and enzyme leakage remarkably decreased. The protection was concentration-dependent and the whole structure of the molecule was required, since carnitine alone was found less effective and propionate had no effect. In the absence of hydrogen peroxide L-propionyl carnitine increased heart performance. The effect of L-propionyl carnitine on oxidative stress could account for the beneficial effect of this substance in different models of ischaemic injury. L-propionyl carnitine increases the cardiac performance and protects the rat heart from peroxidation through metabolic and antiperoxidative mechanisms.

Animals↗
PubMed1992

[Effects of oxygen free radicals on the function of the cardiac sarcoplasmic reticulum].

Peroxidative stress, exerted by oxygen free radicals, seems to be an important mechanism of the ischemia-reperfusion myocardial damage. In the present study we evaluated the modifications of sarcoplasmic reticulum function subjected to peroxidation by ferric ions. A subcellular fraction enriched in sarcoplasmic reticulum was obtained from rabbit hearts by homogenization and differential centrifugations. Sarcoplasmic reticulum vesicles were peroxidated through incubation for 5 min at 37 degrees C in presence of ferric cloride (FeCl3) ranging in concentration between 0.3 and 0.9 mM. Peroxidation of sarcoplasmic reticulum vesicles determined a dose-dependent reduction of Ca-uptake (39.2 +/- 10.3, 36.5 +/- 9.9, 28.9 +/- 8.4 and 18.8 +/- 8.2 nmol/min/mg in presence of 0, 0.3, 0.6 e 0.9 mM FeCl3; NS, p less than 0.05 and less than 0.01, respectively) which was paralleled by an increase in the production of malondialdehyde, an index of lipid peroxidation (1.0 +/- 1.0, 7.0 +/- 3.2, 14.1 +/- 3.9 and 27.0 +/- 4.7 nmol/mg in presence of 0, 0.3, 0.6 e 0.9 mM FeCl3; p less than 0.05, less than 0.01 and less than 0.01, respectively). Depression of Ca-uptake was not accounted for by modifications of Ca-ATPase activity or membrane aspecific permeability to Ca++ ions, since these parameters were not affected by exposure to 0.3-0.9 mM FeCl3. On the contrary, the responsiveness of Ca-release channels to the specific inhibitor ryanodine was greatly altered, even at lower FeCl3 concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Effects of verapamil, gallopamil, diltiazem and nifedipine on sarcoplasmic reticulum function in rat heart.

We investigated the effect of the calcium antagonists verapamil, gallopamil, diltiazem and nifedipine on cardiac sarcoplasmic reticulum function. In a cell-free homogenate from rat hearts, oxalate-supported Ca uptake was stimulated by verapamil, gallopamil and diltiazem at concentrations in the order of 10 nM to 100 nM, while higher concentrations were ineffective. Nifedipine was also ineffective. Peak stimulation of Ca uptake averaged 15-20% of control. Ca uptake is the difference between active Ca transport by Ca-ATPase and passive efflux through sarcoplasmic reticulum channels. In the presence of 300 microM ryanodine, which blocks sarcoplasmic reticulum channels, Ca uptake increased by 50%, but no further stimulation was produced by the addition of any calcium antagonist, at concentrations ranging from 1 nM to 100 microM. In a fraction enriched in sarcoplasmic reticulum, no drug affected the activity of Ca-ATPase at concentrations able to stimulate Ca uptake. We conclude that low concentrations of verapamil, gallopamil and diltiazem reduce Ca efflux through the Ca channels of the sarcoplasmic reticulum. Such an action might contribute to the clinical effect of these drugs.

Animals↗
PubMed1992

Surgical treatment of hilar bile duct carcinoma. Clinical and pathological studies.

Resection of the extrahepatic bile tract for hilar bile duct carcinoma was performed at the PLA General Hospital, with a resectability rate of 62% (31/50) and no operative mortality. Hepatic lobectomy was performed at the same time in 16 cases (51.6%). Reoperative resections were successfully done in 5 cases; 4 cases are still living 1-4 years after the second operation. The cause of late death was mainly biliary infection due to local recurrence and bile duct obstruction. The median survival period was 15 months. 32 cases were studied pathologically, of which 27 were resected surgical specimens and 5 autopsies. The tumors were histologically classified into 4 types: papillary adenocarcinoma (6 cases); well differentiated adenocarcinoma (21); poorly differentiated adenocarcinoma (3); and simple carcinoma (2). The importance of early diagnosis of hilar bile duct carcinoma at its subclinical stage before appearance of clinical jaundice is stressed.

Adenocarcinoma↗
PubMed1992

[Pathological study on 10 cases of inflammatory pseudotumour of the liver].

Histopathological changes of 10 cases of resected inflammatory pseudotumour of liver were observed. These cases were considered to be the primary liver carcinomas or malignant tumours clinically. Morphologically, the inflammatory pseudotumour of liver exhibited varied histological features, including plasma cell granuloma, xanthogranuloma, fibrous proliferation, endophlebitis, necrosis etc. All these cases showed the characteristics of an inflammatory proliferative mass. The causes and the diagnosis criteria of inflammatory pseudotumours of liver were briefly discussed.

Adolescent↗
PubMed1991

Increased DNA binding and transcriptional activity associated with transcription factor Sp1 in K562 cells transfected with the myeloid-specific c-fes tyrosine kinase gene.

Myeloblast cell line K562, when stably transfected with the human genomic c-fes sequence encoding a proto-oncogene tyrosine-protein kinase, acquires the characteristics of more mature granulocytic cells (WS-1 cells) and the ability to undergo differentiation (Yu, G., Smithgall, T. E., and Glazer, R. I. (1989) J. Biol. Chem. 264, 10276-10281). To explore the role of transcription factors in the differentiation process, WS-1 cells were analyzed for the presence of DNA-binding proteins capable of interacting with the 5'-long terminal repeat (LTR) region of human immunodeficiency virus (HIV)-1, that contains the binding sequences for transcription factors Sp1 and NFKB. Southwestern blotting and mobility shift assays revealed the presence of Sp1 in K562 and WS-1 cells. The DNA-binding activity of Sp1 was significantly greater in WS-1 cells than in K562 cells, despite the detection by immuno-blotting of equivalent quantities and degrees of heterogeneity of Sp1 in both cell lines. DNA footprinting of the HIV-1 5'-LTR demonstrated that two of the three Sp1-binding sites and both NFKB binding sequences were protected by nuclear extracts from WS-1 cells, while no protection was afforded by nuclear extracts from K562 cells. Analysis of transcription in vitro by primer extension revealed enhanced initiation of transcription from the HIV-1 5'-LTR by nuclear extracts from WS-1 cells, but not from K562 cells. These data indicate that the response evoked by the c-fes tyrosine-protein kinase leads to enhanced DNA binding activity of Sp1 and NFKB, that results in the activation of transcription from the HIV-1 5'-LTR.

Blotting, Southern↗
PubMed1991

Analysis of Fc gamma RIII (CD16) membrane expression and association with CD3 zeta and Fc epsilon RI-gamma by site-directed mutation.

Two genes encode Fc gamma RIII (CD16), a low affinity FcR for IgG. CD16-I is expressed as a phosphatidylinositol glycan-anchored membrane glycoprotein on neutrophils, whereas CD16-II is a transmembrane-linked glycoprotein on NK cells. Membrane anchoring is determined by codon 203. Site-directed mutation of codon 203 and transient expression of these cDNA in COS-7 cells indicated that Phe, Ile, Leu, and Val permit transmembrane expression, whereas Ser, Thr, Tyr, Asn, Gly, Ala, Asp and Lys enable phosphatidylinositol-glycan attachment. Thus, the involvement of amino acid 203 in membrane anchoring cannot be explained simply on the basis of size, charge, or polarity of the amino acid side groups at this site. Efficient expression of CD16-II in COS-7 cells requires co-transfection with either CD3 zeta or Fc epsilon RI-gamma. Truncation of the cytoplasmic segment of CD16 failed to affect association with CD3 zeta. CD3 zeta and Fc epsilon RI-gamma with truncated cytoplasmic segments were also able to facilitate membrane expression of CD16-II, implicating the transmembrane segments as the interaction site between CD16-II and CD3 zeta or Fc epsilon RI-gamma. Prior studies have suggested that the acidic residue in the CD3 zeta transmembrane segment may be important for the association of CD3 zeta complexes. Although site-directed mutation of CD3 zeta-Asp36 to Glu, Leu, or Val retained the ability to permit membrane expression of CD16-II, quantitatively the wild-type CD3 zeta-Asp36 provided optimal levels of expression, consistent with conservation of this amino acid in mouse and human CD3 zeta.

Antigens, CD↗
PubMed1991

A comparison of the central nervous system effects of caffeine and theophylline in elderly subjects.

1. The effects of oral administration of 250 mg caffeine or theophylline and placebo on subjective ratings and psychological test performance were studied in a double-blind crossover experiment in 20 healthy elderly subjects. 2. Performance on the continuous attention task showed a significant improvement compared with placebo with both active treatments. Performance with caffeine was significantly better than with theophylline. Mean error index scores (normalised AUCs) were: placebo--0.130; caffeine--0.083; theophylline--0.093. No other objective measure shows significant treatment effects. 3. Subjective ratings showed that subjects felt significantly more alert on caffeine than on either theophylline or placebo. Subjects also rated themselves as more energetic and interested on caffeine than on placebo. 4. Plasma concentrations of caffeine were lower than those of theophylline (mean 5.76 and 8.72 mg l-1 respectively at 2 h post-drug. 5. These results suggest that caffeine is a more potent CNS stimulant than theophylline.

Aged↗
PubMed1991

Screening for sleep apnea using pulse oximetry and a clinical score.

Confirmation of the diagnosis of OSA currently requires overnight polysomnography. This study evaluates the usefulness of pulse oximetry together with a clinical score in identifying OSA. Forty patients were assigned a clinical score based on the presence or absence of loud snoring, observations of interrupted breathing during sleep, hypersomnolence, obesity and essential hypertension. Each underwent a night of domiciliary pulse oximetry followed by nocturnal polysomnography. Significant OSA was confirmed in 26. All 15 patients with positive pulse oximetry tracings had significant OSA (apnea index greater than or equal to 10). Five of eight with negative tracings were also shown to have significant OSA along with six of the seven patients with inadequate or indeterminate tracings. Clinical scores were significantly different for those with and without OSA. This study confirms the usefulness of nocturnal pulse oximetry in establishing the diagnosis of OSA and highlights the value of a clinical score in improving its sensitivity as a screening tool.

Adult↗
PubMed1991

Transfection with protein kinase C alpha confers increased multidrug resistance to MCF-7 cells expressing P-glycoprotein.

Cross-resistance to anticancer drugs, termed multidrug resistance (mdr), has been functionally associated with the expression of a plasma membrane energy-dependent efflux pump, termed P-glycoprotein, the product of the mdr1 gene. When MCF-7 breast carcinoma cells were transfected with the human mdr1 gene (BC-19 cells), they expressed levels of P-glycoprotein equivalent to those of cells selected for resistance to doxorubicin (MCF-7/ADR) but exhibited 10- to 50-fold less resistance to doxorubicin and vinblastine. We have now demonstrated that when BC-19 cells were stably transfected with protein kinase C alpha (PKC alpha), resistance to doxorubicin and vinblastine was increased; wild-type MCF-7 cells transfected with PKC alpha did not exhibit any change in drug resistance. Increased resistance in PKC alpha-transfected BC-19 cells was associated with enhanced PKC activity and phosphorylation of P-glycoprotein and decreased drug accumulation. The PKC activator, phorbol dibutyrate, further increased resistance to doxorubicin and stimulated P-glycoprotein phosphorylation. These results demonstrate that transfection of P-glycoprotein-expressing cells with PKC resulted in increased mdr and that PKC may have served as an important modulator of this process.

ATP Binding Cassette Transporter, Subfamily B, Mem↗