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Biomedical subjects

F Lin

Publications and source records attributed to F Lin.

At least 55 records · Page 3Linked to original sources
PubMed2000

[The clinical significance of lung resistance protein (LRP) gene expression in patients with acute leukemia].

OBJECTIVE: To investigate the relationship between the expression of lung resistance protein (LRP) gene and drug resistance in patients with acute leukemias (AL). METHODS: Semi-quantitative reverse transcriptase-polymerase chain reaction (RT-PCR)was used to examine the expression of LRP gene in AL patients and 15 normal subjects. Beta(2) microglobulin (beta(2)MG) was used as internal reference. LRP/beta(2)MG ratio >or= 0.3 was defined as LRP positive. RESULTS: The positivity percentage of LRP gene expression in newly diagnosed group was 32.4%. The first complete remission rate was 84.0% and 33.0% in LRP negative and LRP positive patients, respectively. The difference was significant (P < 0.005). The expression level of LRP mRNA and the positivity percentage of LRP in relapsed/refractory group were significantly higher than that in newly diagnosed group (P < 0.01). The expression level of LRP gene in normal subjects and long-term survival groups was very low and correlated with FAB subtypes. The mdr-1 gene was examined simultaneously in 61 AL patients. No significant correlation was found between the expression of LRP and mdr-1 gene (P > 0.5). Coexpression of LRP and mdr-1 genes in the same AL patient might result in the worst prognosis. CONCLUSION: High expression of LRP gene leads to clinical drug resistance and is an unfavorable factor to AL patients of prognosis.

Acute Disease↗
PubMed2000

[P53 delta 37 protein exhibits 3'-5' exonuclease activity].

Mummenbrauer et al. (1996) found that P53 protein exhibits 3'-5' exonuclease activity. This exonuclease activity is intrinsic to wildtype P53 protein, dependent on Mg2+, and it can be inhibited by addition of 5 mmol/L nucleoside monophosphates. In the present study, we intended to know whether mutated P53 protein--P53 delta 37 has this 3'-5' exonuclease activity or not. The results reveal that P53 delta 37 also has 3'-5' exonuclease activity. It has more protein and more exonuclease activity, but this activity can not be inhibited by guanine monophosphate. There are many processes related to exonuclease activity in mammalian cells; for example, DNA replication, DNA recombination and DNA repair. The exonuclease activity of P53 delta 37 protein may be important in these processes.

Exodeoxyribonuclease V↗
PubMed2000

[The influence of probe geometry on the sensitivity of tissue oximeter using near infra-red spectroscopy].

Based on the modified Lambert-Beer law under scattering media, near infra-red spectroscopy tissue oximeter measures the changes of absorber concentrations (such as oxy-hemoglobin, deoxy-hemoglobin, cytochrome aa3). This is made possible by recording the optical density change under different physiological status. This paper describes the average penetration depth, average photon path-length and spatial sensitive profile in multi-layered tissue model using Monte-Carlo method. The result shows the probe geometry of the sensor, which is the separation between the light source and the detector, has a great influence on the sensitivity of measurement. Increasing this separation properly allows the improvement of the sensitivity of measurement and the increase of the probability of looking at oxygenation deep under the surface tissue. But this improvement is limited by the decrease of signal-noise ratio. Optimum probe spacing should be estimated for special tissue structure.

Humans↗
PubMed1999

Bcr: a negative regulator of the Bcr-Abl oncoprotein.

Chronic myelogenous leukemia is typically characterized by the presence of the Philadelphia chromosome (Ph) in which 5' portions of the BCR gene are fused to a large portion of the ABL gene. Our studies and those of others indicate that Bcr sequences within the Bcr-Abl oncoprotein are critically involved in activating the Abl tyrosine kinase and actively participate in the oncogenic response, which is generated by the Bcr-Abl oncoprotein. We investigated the role of the Bcr protein in the oncogenic effects of Bcr-Abl. Reduction of the level of the Bcr protein by incubating cells with a 3' BCR anti-sense oligodeoxynucleotide increased the growth rate and survival of hematopoietic cell lines expressing Bcr-Abl. Also, enforced expression of Bcr in Bcr-Abl cell lines strongly reduced transformation efficiency. Induction of Bcr expression drastically reduced the phosphotyrosine content of Bcr-Abl in Rat-1 fibroblasts transformed by P185 BCR-ABL and in hematopoietic cells expressing P210 Bcr-Abl within days following induction of Bcr. Rat-1/P185 cells maintained for three weeks after Bcr induction had dramatically reduced amounts of phosphotyrosine proteins compared to cells in which Bcr expression was repressed by the addition of Tet. In contrast Bcr expression did not decrease the phosphotyrosine content of either v-Src or activated Neu tyrosine kinase. Importantly, the phosphotyrosine content of total P160 BCR (induced plus endogenous) was strongly reduced by inducing expression of Bcr, indicating that the induced Bcr protein was not a target of the tyrosine kinase activity of Bcr-Abl but instead functioned as an inhibitor of Bcr-Abl. These results show that the Bcr protein can function as a negative regulator of Bcr-Abl, but that the inhibitory effects of Bcr are dependent on achieving an elevated level of Bcr expression relative to Bcr-Abl.

Animals↗
PubMed1999

Decreased (45)Ca(2)(+) uptake in P/Q-type calcium channels in homozygous lethargic (Cacnb4lh) mice is associated with increased beta3 and decreased beta4 calcium channel subunit mRNA expression.

The mutated gene in the lethargic (Cacnb4lh) mouse model of absence seizures encodes the beta4 subunit of voltage-gated calcium channels (VGCCs), leading to decreased mRNA expression of a beta4 subunit that is truncated and cannot bind to alpha1 subunits of VGCCs. In this study we accomplished two goals. First, we studied the functional consequence of altered VGCCs by examining the effects of a selective P/Q-type channel antagonist on KCl-induced (45)Ca(2)(+) uptake in brain synaptosomes from Cacnb4lh homozygotes and non-epileptic controls (designated by +/+). We found that depolarization-induced (45)Ca(2)(+) uptake was significantly reduced in the brains of Cacnb4lh homozygotes, and that the reduced uptake was completely accounted for by reduced function of P/Q-type calcium channel. Second, we examined VGCC subunit composition to determine if other subunits were altered in addition to the mutation affecting beta4 subunits in Cacnb4lh homozygotes; when alterations were found, we determined if they were regional or global. We used in situ hybridization histochemistry (ISHH) to analyze the neuro-anatomic distribution of beta4, beta1b, beta2, beta3, alpha1A, alpha1B, alpha1C, alpha1E, and alpha1G subunit mRNAs in brain sections from matched Cacnb4lh homozygotes and +/+ controls. Our results indicated that expression of beta4 subunit mRNA is globally reduced throughout the brains of Cacnb4lh homozygotes, in contrast to a small but significant global increase in the expression of beta3 subunit mRNA. There were no significant differences in expression of the other VGCC subunit mRNAs examined. Together, these findings indicate that a host of changes in VGCC subunit composition accompany reduced function of P/Q-type channels in homozygous lethargic mice.

Animals↗
PubMed1999

Age-related relationship between mRNA expression of GABA(B) receptors and calcium channel beta4 subunits in cacnb4lh mice.

In previous studies we found increased GABA(B) receptor number in 8-week-old homozygous Cacnb4lh mice compared to nonepileptic (+/+) littermates. In this study, we examined the relationship between Cacnb4 and GABA(B) receptor mRNA expression in brains from Cacnb4lh homozygotes and (+/+) controls. We found a significant correlation between the magnitude of increased GABA(B) receptor and decreased Cacnb4 mRNA expression in 8-week-old mice. In contract, in 6-month-old mice, there was no change in GABA(B) receptor or Cacnb4 mRNA expression. These findings suggest that the factor(s) responsible for decreased Cacnb4 and increased GABA(B) receptor mRNA expression abate in older mice.

Aging↗
PubMed1999

Phe310 in transmembrane VI of the alpha1B-adrenergic receptor is a key switch residue involved in activation and catecholamine ring aromatic bonding.

Pharmacophore mapping of adrenergic receptors indicates that the phenyl ring of catecholamine agonists is involved in receptor binding and activation. Here we evaluated Phe310, Phe311, and Phe303 in transmembrane VI (TMVI), as well as Tyr348 in TMVII of the alpha1B-adrenergic receptor (alpha1B-AR), which have been implicated in a catechol-ring interaction. Neither catecholamine docking studies nor mutagenesis studies of Phe311, Phe303, or Tyr348 supported a role for these residues in catechol-ring binding. By contrast, docking studies indicated that the Phe310 side chain is well positioned to interact with the catechol-ring, and substituted cysteine accessibility method studies revealed that the side chain of the 310, but not 311 residue, is both solvent accessible and directed into the agonist-binding pocket. Also, saturation mutagenesis of both Phe310 and Phe311 revealed for the former, but not for the latter, a direct relationship between side chain volume and agonist affinity, and that aromaticity is essential for wild-type agonist binding, and for both wild-type agonist potency and efficacy. Moreover, studies of Phe310 mutants combined with a previously described constitutively active alpha1B-AR mutant, A293E, indicated that although not required for spontaneous receptor isomerization from the basal state, R, to a partially activated conformation R', interaction of Phe310 with catecholamine agonists is essential for isomerization from R' to the fully activated state, R.

2-Hydroxyphenethylamine↗
PubMed1999

Beta-arrestin-dependent formation of beta2 adrenergic receptor-Src protein kinase complexes.

The Ras-dependent activation of mitogen-activated protein (MAP) kinase pathways by many receptors coupled to heterotrimeric guanine nucleotide binding proteins (G proteins) requires the activation of Src family tyrosine kinases. Stimulation of beta2 adrenergic receptors resulted in the assembly of a protein complex containing activated c-Src and the receptor. Src recruitment was mediated by beta-arrestin, which functions as an adapter protein, binding both c-Src and the agonist-occupied receptor. beta-Arrestin 1 mutants, impaired either in c-Src binding or in the ability to target receptors to clathrin-coated pits, acted as dominant negative inhibitors of beta2 adrenergic receptor-mediated activation of the MAP kinases Erk1 and Erk2. These data suggest that beta-arrestin binding, which terminates receptor-G protein coupling, also initiates a second wave of signal transduction in which the "desensitized" receptor functions as a critical structural component of a mitogenic signaling complex.

Adrenergic beta-Agonists↗
PubMed1999

Dynamic complexes of beta2-adrenergic receptors with protein kinases and phosphatases and the role of gravin.

Signals mediated by G-protein-linked receptors display agonist-induced attenuation and recovery involving both protein kinases and phosphatases. The role of protein kinases and phosphatases in agonist-induced attenuation and recovery of beta-adrenergic receptors was explored by two complementary approaches, antisense RNA suppression and co-immunoprecipitation of target elements. Protein phosphatases 2A and 2B are associated with the unstimulated receptor, the latter displaying a transient decrease followed by a 2-fold increase in the levels of association at 30 min following challenge with agonist. Protein kinase A displays a robust, agonist-induced association with beta-adrenergic receptors over the same period. Suppression of phosphatases 2A and 2B with antisense RNA or inhibition of their activity with calyculin A and FK506, respectively, blocks resensitization following agonist removal. Recycling of receptors to the plasma membrane following agonist-promoted sequestration is severely impaired by loss of either phosphatase 2B or protein kinase C. In addition, loss of protein kinase C diminishes association of phosphatase 2B with beta-adrenergic receptors. Overlay assays performed with the RII subunit of protein kinase A and co-immunoprecipitations reveal proteins of the A kinase-anchoring proteins (AKAP) family, including AKAP250 also known as gravin, associated with the beta-adrenergic receptor. Suppression of gravin expression disrupts recovery from agonist-induced desensitization, confirming the role of gravin in organization of G-protein-linked signaling complexes. The Ht31 peptide, which blocks AKAP protein-protein interactions, blocks association of beta-adrenergic receptors with protein kinase A. These data are the first to reveal dynamic complexes of beta-adrenergic receptors with protein kinases and phosphatases acting via an anchoring protein, gravin.

A Kinase Anchor Proteins↗
PubMed1999

Atypical glandular cells of undetermined significance in cervical cytologic findings.

OBJECTIVE: Our purpose was to increase our understanding of the clinical significance of atypical glandular cells of undetermined origin. STUDY DESIGN: All cytologic Papanicolaou smears were reviewed and classified within the context of the Bethesda classification system. Charts of all patients with a diagnosis of atypical glandular cells of undetermined origin were reviewed for previous medical history, diagnostic study, histologic diagnosis, and prior Papanicolaou smear abnormalities. RESULTS: The incidence of atypical glandular cells of undetermined origin in 76,018 Papanicolaou smears was 0.196%. We reviewed 133 patient medical records with cytologic diagnoses. Eighty of these patients have had appropriate follow-up. Thirty-six (45%) of these were found to have significant histologic abnormalities, including 6 patients with cervical intraepithelial neoplasia, grades 2 and 3, and 4 invasive cancers. CONCLUSION: The frequency of underlying serious histologic changes is much greater in atypical glandular cells than in atypical squamous cells of undetermined significance. On the basis of our results, we believe that all patients with atypical glandular cells should undergo intensive evaluation including colposcopy, cervical biopsy, and endocervical curettage. When diagnosis cannot be clearly established, patient should undergo endometrial biopsy.

Adolescent↗
PubMed1999

Protoporphyrin IX-sensitized photoinactivation of 5-aminolevulinate-treated leukemia cells: effects of exogenous iron.

Photodynamic therapy with 5-aminolevulinic acid (ALA) is based on metabolism of ALA to a photosensitizing agent, protoporphyrin IX (PpIX), in tumor cells. Photosensitivity of target cells may be influenced by mitochondrial iron levels because ferrochelatase-catalyzed insertion of Fe2+ into PpIX converts it to heme, a nonsensitizer. To investigate this prospect, we exposed L1210 cells (approximately 10(6)/mL in 1% serum-containing medium) to a lipophilic iron chelate, ferric-8-hydroxyquinoline (Fe[HQ]2, 0.5 microM), prior to treating with ALA (0.2 mM, 4 h) and irradiating with broadband visible light. When Fe(HQ)2 was added to cells immediately or 1 h before ALA, the initial rate of photokilling, as measured by thiazolyl blue (mitochondrial dehydrogenase) assay, was markedly less than that of non-iron controls. The HPLC analysis of cell extracts indicated that ALA-induced PpIX was at least 50% lower after this Fe(HQ)2 treatment, presumably explaining the drop in photolethality. By contrast, cells treated with ALA and light 20 h after being exposed to Fe(HQ)2 contained the same amount of PpIX as non-iron controls and were photoinactivated at nearly the same rate. The 20 h delayed cells contained approximately 12 times more immunodetectable ferritin heavy subunit than controls or 1 h counterparts, which could account for the disappearance of iron's antisensitization effects in the former. Consistent with this idea, the short-term effects of Fe(HQ)2 on ALA-induced sensitization were found to be blunted significantly in ferritin-enriched cells. The Fe(HQ)2 produced strikingly different results when cells were sensitized with exogenous PpIX, stimulating photokilling after short-term contact but inhibiting it after long-term contact while having no significant effect on the level of cell-associated PpIX in either case. Thus, iron can have diverse effects on PpIX-mediated photokilling, depending on contact time with cells and whether the porphyrin is metabolically derived or applied as such.

Aminolevulinic Acid↗
PubMed1999

Vancomycin use in 2 Ontario tertiary care hospitals: a survey.

OBJECTIVE: Use of vancomycin is a risk factor for acquiring vancomycin-resistant enterococci (VRE). To optimize the use of vancomycin in hospitals, the Hospital Infection Control Practices Advisory Committee (HICPAC) published recommendations in 1995. The objectives of this study were to determine the frequency, indications, and risk factors for inappropriate inpatient vancomycin prescriptions before and after publication of the HICPAC recommendations. DESIGN: Cross-sectional study. SETTING: Two tertiary care hospitals in Ontario. INTERVENTIONS: Vancomycin prescriptions were randomly sampled and hospital chart view performed for two 12-month periods, one before and one after publication of the HICPAC recommendations on vancomycin use. RESULTS: Based on the review of 189 charts from hospital A and 190 from hospital B, there was no significant change in the proportion of inappropriate vancomycin prescriptions at either hospital from before publication of the HICPAC recommendations to afterward (63% v. 71% at hospital A, p = 0.21; 48% v. 37% at hospital B, p = 0.11). In 51% of all vancomycin prescriptions, the drug was prescribed instead of another antibiotic because of a recorded penicillin allergy. Surgical prophylaxis with more than 1 or 2 doses of vancomycin accounted for 66% (hospital A) and 58% (hospital B) of inappropriate prescriptions. In a multivariate analysis, surgical prophylaxis remained a significant risk factor for inappropriate use of vancomycin at both hospitals (odds ratio [OR] 5.6, 95% confidence interval [CI] 2.8 to 11.3, p = 0.01 for hospital A; OR 13.9, 95% CI 4.9 to 39.5, p = 0.01 for hospital B). Prescription by the orthopedic service also remained a significant risk factor in the final logistic regression model for hospital B (OR 3.9, 95% CI 1.1 to 13.9, p = 0.01). CONCLUSIONS: A high proportion of vancomycin prescriptions, surveyed before and after publication of the HICPAC recommendations on vancomycin use, were inappropriate. Excessive vancomycin use in surgical prophylaxis was an important factor. Our findings suggest that the use of standardized peri-operative order forms and of penicillin-allergy testing may help optimize vancomycin use in tertiary care hospitals.

Anti-Bacterial Agents↗
PubMed1999

Relationship between bone mineral density and polymorphism of the estrogen receptor gene in healthy postmenopausal women in China.

OBJECTIVE: To investigate the possible relationship between bone mineral density and polymorphism of the estrogen receptor (ER) gene in Shanghai healthy postmenopausal women. METHODS: 250 unrelated healthy postmenopausal women were selected for bone mineral density (BMD) determination by Dual energy X-ray absorptiometry (DEXA) and polymorphism of estrogen receptor gene analyses by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). RESULTS: Pvu II polymorphisms of ER gene was associated with low Troch BMD (P = 0.0153) while there was no significant relationship between Xba I polymorphism of ER gene and BMD at any of skeletal sites included in the present study, and the combination of Pvu II and Xba I polymorphisms of ER gene was significantly associated with both low Lumbar 2-4 (P = 0.0369) and Troch (P = 0.0384) BMD. Multiple stepwise regression analysis also indicated that two combined polymorphisms were correlated significantly with Lumbar 2-4 BMD (P = 0.0254) while this correlation was not revealed at any other skeletal sites. CONCLUSION: There is significant relationship between the polymorphism of ER gene and both Lumbar 2-4 BMD and Troch BMD. It is significant to explore the pathogenesis of osteoporosis and to prevent the development of osteoprosis by use of molecular genetics.

Absorptiometry, Photon↗
PubMed1998

Hemin-enhanced resistance of human leukemia cells to oxidative killing: antisense determination of ferritin involvement.

Human HL-60 cells exhibited a strong hyperresistance to the lethal effects of photodynamic activity (singlet oxygen) or glucose oxidase activity (hydrogen peroxide) 16-20 h after being exposed to hemin (ferriprotoporphyrin IX). Hyperresistance was accompanied by the overproduction of immunodetectable ferritin, predominantly the heavy (H) subunit, which exhibits ferroxidase activity. Cells that had been enriched in apoferritin via pinocytotic uptake showed similar hyperresistance to both types of oxidative challenge. On the other hand, preincubating cells with hemin in the presence of a phosphorothioate-linked antisense oligodeoxynucleotide against H-ferritin mRNA resulted in a strong diminution in both hyperresistance and H-ferritin induction. No effects were seen when a scrambled order oligodeoxynucleotide of the same base composition was used, confirming that the antisense oligomer had specifically inhibited H-ferritin translation. These results indicate that induced ferritin played a crucial role in the observed cytological responses. Enhanced oxidant resistance is attributed to the ability of this ferritin to rapidly sequester and incapacitate redox-active iron.

Apoferritins↗