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PubMedDate not supplied

Serum protein polymorphisms (GC, TF, and PI subtypes) in the Basque population of Alava.

Group-specific component (GC), transferrin (TF) and alpha-1-antitrypsin (PI) polymorphisms have been studied in the Basque population of Alava. The following gene frequencies were found: GC*1S = 0.525, GC*1F = 0.109, GC*2 = 0.366; TF*C1 = 0.793, TFC*2 = 0.171, TF*C3 = 0.032, TF*B = 0.003; PI*M1 = 0.611, PI*M2 = 0.164, PI*M3 = 0.101, PI*M4 = 0.019, PI*S = 0.101, PI*T = 0.003, PI*Z = 0.002. These results show that there is heterogeneity within the Basque population. In comparison with other populations from the Iberian Peninsula, the Basques from Alava show significant differences only for the PI system.

Alleles↗
PubMed2005

Population pharmacokinetic-pharmacodynamic modeling of TF-505 using extension of indirect response model by incorporating a circadian rhythm in healthy volunteers.

The pharmacokinetic-pharmacodynamic (PK-PD) relationship of the newly developed drug, (-)-(S)-4-[1-[4-[1-(4-isobutylphenyl)butoxy]benzoyl]indolizin-3-yl]butyric acid (TF-505), was characterized via a population approach in early human study. Healthy volunteers were divided into six groups. The groups received four single doses (25, 50, 75 or 100 mg) and 2 multiple doses (12.5 or 25 mg) of TF-505, respectively. Dihydrotestosterone (DHT) data were collected to assess TF-505 pharmacodynamics. Population PK/PD modeling of TF-505 was performed via mixed-effects modeling using the NONMEM software package. The final PK-PD model incorporates a two-compartment PK model and an extended indirect PD model. The population PK parameters were 0.197 h(-1) for the k(a), 0.0678 h(-1) for k(e), 12.5 l for V(c), 0.0645 h(-1) for k(12), 0.0723 h(-1) for k(21). Extension of indirect response model by incorporating a time-dependent periodic function for k(in) takes into account the chronopharmacologic rhythms (I(max): 0.706+/-0.297, IC(50): 1.01+/-1.64 (microg/ml), k(out): 0.221+/-0.0486 (h(-1)), R(m): 20.4+/-8.08 (% h(-1)), R(amp): 5.06+/-3.43 (% h(-1)), T(z): 5.01+/-0.407 (h) (Population mean+/-S.E.)). R(m) is the mean DHT synthesis rate, R(amp) is the amplitude of the DHT synthesis rate, and T(z) is the acrophase time, signifying maximum synthesis rate. The present study represents a successful population PK-PD model using the full data from early human studies. The population parameters thus obtained could provide useful indicators for the determination of dosage regimens in exploratory studies in patient populations.

Adult↗
PubMed2004

Therapeutic angiogenesis by autologous bone marrow cell implantation for refractory chronic peripheral arterial disease using assessment of neovascularization by 99mTc-tetrofosmin (TF) perfusion scintigraphy.

We investigated efficacy and safety of implantation of autologous bone marrow mononuclear cells plus platelets, including endothelial progenitor cells (EPCs), for recovering refractory chronic peripheral arterial disease (PAD) using visual and quantitative analyses by 99mTc-tetrofosmin (TF) perfusion scintigraphy, and also investigated various quantitative assessments objectively. We performed 12 consecutive cases and 19 limbs and hands with severe chronic PAD that were almost Fontaine class IV (11/12 cases, about 92%) in this trial. This treatment was very effective in relieving severe pain of PAD, especially for Buerger's disease. We used a visual analog scale (VAS) for measurement of pain level. The maximum pain level before implantation was 66.5+/-5.0 mm, and it decreased to 12.1+/-2.2 mm after implantation (p < 0.001). Rest pain in legs and fingers was resolved in 11 cases (11/12 cases, 92%). All patients could measure pain-free walking time on a treadmill, which improved remarkably (140+/-53 s before implantation vs. 451+/-74 s after implantation, p = 0.034). Resting ankle brachial pressure index (ABI) in legs implanted with bone marrow mononuclear cells was also improved (0.65+/-0.08 before implantation vs. 0.73+/-0.07 after implantation, p = 0.055). According to 99mTc-TF perfusion scintigraphy, the proximal area (region from knee to ankle) was 1.32+/-0.10 before implantation versus 1.56+/-0.11 after implantation (p = 0.007). 99Tc-TF perfusion scintigraphy in the distal area (region from ankle to end of toes, or from wrist to end of fingers) was 0.79+/-0.06 before implantation versus 0.83+/-0.06 after implantation (p = 0.29). Ischemic legs and hands that were injected showed increased perfusion blood flow. 99mTc-TF perfusion scintigraphy was effective to estimate visual and quantitative analysis of collateral vessels in neovascularization. We were successful with this new treatment for the most severe, chronic PAD that was not curable by any of the current treatments. Thus, this therapeutic angiogenesis could be a new strategy for saving severe ischemic limbs and hands.

Aged↗
PubMed1997

[The changes and clinical significance of serum CRP, C3, Tf, and PA in the early postburn stage].

The aim of this study was to investigate the regulation and clinical significance of serum acute phase proteins. The patients were divided into three groups: group I consisted of 11 patients with less than 20% of TBSA; group II 10 patients with 20-50% of TBSA and group III 11 patients with more than 50% of TBSA. Blood samples were taken at 8, 24, 48 and 72 h postburn, and in group III additional blood samples were taken on the 7th, 14th, 21st day or in septic episode. The concentration of CRP and C3, Tf, PA were detected by rate nephelometry, agar immunodiffusion and rocket immunoelectrophoresis respectively. Compared with controls, the peak value of CRP was observed during 48-72 h (P < 0.01), C3 decreased at 8 h and lowest at 24 h. Tf was lowered at 48 h, PA and Tf shared the similar changes. However, all four variables had no marked difference during infection and sepsis. The results showed no correlation between C3 and CRP (r = 0.0885, P > 0.05). The results suggested that: 1. CRP mainly reflected the extent of injury but not sepsis; 2. increased CRP was not the causative factor of decreased C3. Tf reduction accelerated bacterial growth.

Adult↗
PubMedDate not supplied

[Transfection of TF-1 cell line with human bcl-2 proto-oncogene provides short-term survival in absence of GM-CSF without changing the phenotype].

UNLABELLED: Apoptosis is a process genetically controlled. The produce of the bcl-2 gene, bcl-2, is an anti apoptotic protein that is linked to the external membrane of the mitochondria. OBJECTIVE: To explore the possibility that bcl-2 transfection could change phenotype, response to mitogenic factor, and cell morphology on the TF-1 parental cell line and the bcl-2 transfectant TB-1 or TF-1neo. METHODS: We look at the expression of CD13, CD34 and c-Kit surface markers by flow cytometry. We have measured cell proliferation in response to GM-CSF and cell survival after GM-CSF withdrawal by the MTT assay on the same cell lines. Apoptosis was evaluated by the apoptotic membrane blebbing set up at different times after serum and survival factor removal or tolerance to cytotoxic compounds from Justicia spicigera. RESULTS: According with our results, ectopic expression of the bcl-2 gene prevented apoptosis without changes in morphology or phenotype in the absence of GM-CSF and serum or the presence of the extract from Justicia spicigera. Consisting with the Bcl-2 function, we found that Bcl-2 did not change response to GM-CSF. Serum deprivation or GM-CSF withdrawal induces cell death at 36 hours in TF-1 and TF-1neo cells, whereas TB-1 cells undergo apoptotic membrane blebbing after 96 hours under the same conditions. CONCLUSIONS: Taken together, our data indicate that Bcl-2 is a short term anti apoptotic protein in TB-1 cell line, that does not affect response to GM-CSF neither CD13, CD34 nor c-Kit antigen expression.

Cell Line↗
PubMedDate not supplied

Expression of the Thomsen-Friedenreich (TF) antigen in the human placenta.

The Thomsen-Friedenreich (TF) antigen (or, more precisely, epitope; Gal beta 1-3GalNAc-) has been known for a long time as a pancarcinoma antigen. Here we report the immunohistochemical identification of this carbohydrate antigen in the human placenta. Paraffin-embedded placental and decidual tissues of the first, second and third trimester were incubated with different monoclonal antibodies (A78-G/A7 and HH8) directed against the TF-epitope and stained with an immunohistochemistry system. We found a strong expression of the TF-epitope in the first trimester of pregnancy. In addition, we identified an expression of the TF-antigen in the second trimester of pregnancy but only in a few cases a positive staining in the third trimester of pregnancy.

Antigens, Tumor-Associated, Carbohydrate↗
PubMed1999

[Changes of TF and TFPI activities in patients with hypertension or coronary atherosclerotic heart disease].

OBJECT: To investigate the changes of tissue factor (TF) and tissue factor pathway inhibitor(TFPI) activities in patients with hypertension or coronary atherosclerotic heart (CAH) disease. METHODS: TF activity was measured by two-stage assay, and TFPI activity was detected according to Sandset's method. RESULTS: Plasma TF activity in both patients with hypertension and patients with CAH disease was higher than that of normal control(P < 0.05). CONCLUSION: Hypercoagulative state may be involved in the pathogenetic processes of hypertension and CAH diseases. TF and TFPI activities have the likelihood to become the accessory diagnostic indexes for hypertension and CAH diseases.

Adult↗
PubMed2002

[Tissue factor (TF) and inhibitor (TFPI) concentrations in patients with urinary tract tumors and haematological malignancies].

The aim of study was to evaluate TF activity and TFPI concentration in patients with haematological malignancies and urinary tract tumors. TFPI concentration and activity and TF concentration were measured in 20 patients suffering from acute myeloblastic leukaemia (AML), 21 patients with chronic myelogenous leukaemia (CML), 17 patients with chronic lymphatic leukaemia (CLL), 16 patients with multiple myeloma (MM) and 65 healthy adults. TFPI and TF concentrations were measured also in patients with renal cell carcinoma (n = 12) and bladder cancer (n = 17) and patients with benign prostatic hyperplasia (BPH) (n = 15). Patients with AML, CML, CLL, and cancer revealed elevated TFPI concentrations. Patients with AML, CML, CLL, MM showed decreased TFPI activity. However TFPI concentration correlated inversely with TFPI activity only in the AML group. No significant changes were observed in TF concentrations in all investigated groups.

Biomarkers, Tumor↗
PubMed1992

Serum protein polymorphisms in Arab Moslems and Druze of Israel: BF, F13B, AHSG, GC, PLG, PI, and TF.

We report results of typing two population samples, Israeli Arab Moslems and Arab Druze, for seven serum protein genetic variants. Data are presented in comparison with results for the same markers in a sample of Jordanian Arabs. In Israeli Moslems gene frequencies for BF (n = 169) were BF*S = 0.6361, BF*F = 0.3343, BF*S07 = 0.0296, and BF*1 = 0, and for TF (n = 90) the gene frequencies were: TF*C1 = 0.7167, TF*C2 = 0.2611, and TF*C3 = 0.0222. Allele frequencies for AHSG in Israeli Moslems (n = 155) and Druze (n = 192) were AHSG*1 = 0.9129 and 0.8750 and AHSG*2 = 0.0806 and 0.1250, respectively. Gene frequencies for PLG in Moslems (n = 149) and Druze (n = 190) were PLG*A = 0.4597 and 0.5288 and PLG*B = 0.5101 and 0.4188, respectively. The typing of Israeli Arab Druze (n = 194) for F13B resulted in F13B*1 = 0.8454, F13B*2 = 0.0387, F13B*3 = 0.0979, and F13B*4 = 0.0180. Results on the same population for PI (n = 192) were PI*M1 = 0.7839, PI*M2 = 0.1276, PI*M3 = 0.0781, PI*M4 = 0.0026, and PI*M5 = 0.0026. Observed rare alleles in various systems indicate gene flow from Europe, Africa, and Asia into the Middle East. The results on Arab populations were considered in relation to available population data in the three adjacent continents. The emerging gene frequency profile for Arabs seems to fit with the central geographic and climatic position of the Middle East.

Adolescent↗
PubMed1991

Transferrin polymorphisms in Japanese populations: north-south cline in the distribution of the TF*C2 allele.

Allele frequencies for human transferrin (TF) subtypes were determined using serum samples from Japanese subjects living in Fukui prefecture, Japan, and compared with other Japanese populations using isoelectric focusing (IEF) and immunoblotting. The application of IEF revealed considerable heterogeneity in the TF system, enhancing its potential value for anthropologic and genetic studies. So far, TF subtypes of about 27,000 Japanese individuals from 35 population groups have been analyzed to evaluate the degree of genetic variation at the TF locus. Possible geographic and biologic factors are discussed.

Alleles↗
PubMed1990

[Ecogenetic cause of polymorphism of transferrin (Tf) in various sex and age groups of Russians and Buryats].

The distribution of transferrin (Tf) suballeles have been studied in Russians and Buriats, in connection with sex-age characters. No directional change in Tf suballele frequencies was obtained for age cohorts of Buriats. The tendency for decrease in the Tf allele frequency was noted in oldest age groups of Russians. The differences between Russians and Buriats were conditioned by differences between female subgroups, with respect to transferrins solely. The frequencies of relatively rare Tf alleles (C3, B, D) were higher in female subgroups, as compared with males.

Adult↗
PubMedDate not supplied

Serum protein polymorphisms (HP; TF-, GC- and PI-subtypes) in Sardinia.

Haptoglobin (HP), transferrin (TF), group-specific component (GC) and alpha-1-antitrypsin (PI) polymorphisms have been studied in Sardinia and the following gene frequencies have been found: HP*1 = 0.389, TF*C1 = 0.754, TF*C2 = 0.213, TF*C3 = 0.032, GC*1F = 0.193, GC*1S = 0.546, GC*2 = 0.260, PI*M1 = 0.607, PI*M2 = 0.221, PI*M3 = 0.126, PI*S = 0.040 and PI*Z = 0.006. These findings confirm the genetic uniqueness of Sardinians compared to the other Italian populations.

Adult↗
PubMed1987

Unusual transferrin TF*D mutants in some Congo populations.

Transferrin allele (TF) distribution was investigated in three Bantu and one Babenga Pygmy groups of Congo, by isoelectric focusing on polyacrylamide (PIEF). In comparison with other Black populations, the four groups had a twofold higher TF*D frequency. Three different TF*D mutants were observed, the commonest type of which was identical by PIEF to a *D1 Caucasian allele. The classification of the other two is discussed. The homozygous TF D1 pattern was present in Babenga. The polymorphism of transferrin confirmed the uniqueness of anthropological traits in such Congo populations.

Alleles↗
PubMed1984

The structural gene for transferrin (TF) maps to 3q21----3qter.

A cloned human cDNA for transferrin (TF) was used as hybridization probe in analysing a series of rodent x human somatic cell hybrids for the presence of human TF sequences. The assignment to chromosome 3 was further refined to region 3q21----3qter using hybrids that carried a translocated chromosome 3 and fibroblasts from a patient trisomic for this region. The gene for TF therefore maps to the same region as the gene for transferrin receptor (TFR) thereby defining an iron transport region on 3q2 to which the transferrin-related tumor associated antigen p97 may also belong. It follows that the genes for pseudocholinesterase (CHE1), ceruleoplasmin (CP) and alpha-2HS-glycoprotein (A2HS) which belong to the, as yet unassigned, linkage group of TF, now also map to chromosome 3 in man.

Animals↗
PubMed1994

Negative regulation by the R2 element of the MHC class I enhancer in adenovirus-12 transformed cells correlates with high levels of COUP-TF binding.

The transcriptional down-regulation of the major histocompatibility complex (MHC) class I antigens in adenovirus type 12 (Ad12) transformed cells gives them the potential to escape immunosurveillance and to form tumors. The enhancer of the class I promoter is the target of transcriptional repression which is mediated by the E1A gene of Ad12. The R2 region within the class I enhancer acts as a negative element in Ad12-transformed cells and exhibits a stronger binding activity than is observed in nontumorigenic Ad5-transformed cells, which are not reduced in class I expression. The R2 element contains a nuclear hormone receptor half-site consensus sequence, AGGTCA, which is required for both the binding activity and the ability of R2 to act as a negative element in Ad12-transformed cells. In this study, we show that an orphan hormone receptor protein, COUP-TF, contributes to the differential R2 binding activity observed between Ad12- and Ad5-transformed cells. Additionally, COUP-TF was shown to bind as a dimer to the R2 element and to use the consensus AGGTCA as one half-site and its 3' flanking sequence as a probable second degenerate half-site. Since COUP-TF can act as a transcriptional repressor, we suggest that the higher COUP-TF binding activity to the R2 element in Ad12-transformed cells contributes to down-regulation of class I transcription and, consequently, tumorigenesis.

Adenoviruses, Human↗
PubMed1993

Chicken ovalbumin upstream promoter-transcription factor (COUP-TF) represses transcription from the promoter of the gene for ornithine transcarbamylase in a manner antagonistic to hepatocyte nuclear factor-4 (HNF-4).

Chicken ovalbumin upstream promoter-transcription factor (COUP-TF) and hepatocyte nuclear factor-4 (HNF-4) are orphan members of the steroid/thyroid receptor superfamily and exhibit ubiquitous and liver-enriched tissue distribution, respectively. The gene for rat ornithine transcarbamylase (OTC), an ornithine cycle enzyme, is mainly expressed in the liver and is under the control of the promoter and the 11-kilobase upstream enhancer, both of which are liver-selective. Two sites of the promoter region and two sites of the enhancer region of the OTC gene, as well as the ovalbumin promoter site, were recognized by both HNF-4 and COUP-TF, showing that these two factors have closely related binding specificities. Since HNF-4 activated expression from the OTC promoter in cotransfection analysis, this factor appears to participate in liver-selective activation of the OTC gene. On the other hand, COUP-TF repressed the expression from the OTC promoter, whereas it activated expression from several other promoters. Therefore, COUP-TF plays a dual regulatory role depending on the promoter context. Repression of a tissue-specific promoter by a ubiquitous transactivator and derepression by a related tissue-enriched transactivator is potentially an important mechanism for tissue-specific activation of a gene.

Animals↗
PubMed1996

[Overexpression of bcl-2 suppresses apoptotic cell death of the human leukemic cell line TF-1].

We analyzed the effect of overexpression of bcl-2 gene on cell cycle progression, using the growth factor dependent cell line, TF-1, derived from an erythroleukemia patient. TF-1 (bcl-2) cells, which were transfected with bcl-2 cDNA by the retrovirus vector system, survived and arrested in the G0-1 phase on GM-CSF removal. Centrifugal elutriation studies showed that G0-1-arrested subfraction of TF-1 (bcl-2) reentered the cell cycle with time delay upon GM-CSF re-addition, when compared with TF-1 (mock). A similar delay in cell cycle progression was observed during the recovery phase after 24h-exposure to staurosporine, a protein kinase C(PKC) inhibitor. These results imply functional involvement of bcl-2, both in the GM-CSF and the PKC signal transduction pathway and in G0-1 progression.

Apoptosis↗
PubMed1997

The Thomsen-Friedenreich (TF) antigen: a critical review on the structural, biosynthetic and histochemical aspects of a pancarcinoma-associated antigen.

Within the family of blood-group related carbohydrate antigens the Thomsen-Friedenreich (TF) antigen (or T antigen) is an outstanding member by attracting scientific interest for more than 65 years and by having retained its significance as object of current biomedical research; in particular, as a pancarcinoma-associated antigen. In accordance with its constant or even growing attraction scientists have searched for specific reagents which would allow the unambiguous and sensitive detection of the Thomsen-Friedenreich antigen on cells or tissues. While at the beginning, immunohistochemical work on TF antigen expression was restricted by the limited specificity of plant lectins (peanut lectin) a significant progress has been possible since the introduction of the hybridoma technique. The respective monoclonal antibodies display distinct fine specificities and cellular staining patterns in immunohistochemistry and have contributed to controversial discussions on the organ-characteristic and tumor-associated expression of the TF antigen in some organs. It is the aim of this survey to summarize in the context of its structural and biosynthetic aspects the current knowledge on the tissue expression of the TF antigen as based on the use of peanut agglutinin and monoclonal antibodies and to discuss the findings with regard to their biomedical relevance, in particular, with emphasis on their value in tumor diagnosis.

Antigens, Tumor-Associated, Carbohydrate↗