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At least 919 records · Page 51Linked to original sources
PubMed2002

Human T-cell lymphotropic virus type I Tax activates lung resistance-related protein expression in leukemic clones established from an adult T-cell leukemia patient.

OBJECTIVE: We examined the significance of human T-cell lymphotropic virus type I (HTLV-I) Tax protein-induced resistance to anticancer drugs and the relationship between Tax and multidrug resistance proteins. MATERIALS AND METHODS: S1T cell, a leukemic non-Tax-producing T-cell clone established from an adult T-cell leukemia (ATL) patient, S1TcTax05 and S1TcTax10 clones, transfected with Tax stably expressing cDNA, and S1Tneo, transfected with a neomycin-resistant gene, were examined for Tax-related anticancer drug resistance. Resistance of those cells to the anticancer drugs doxorubicin, etoposide, cisplatin, and vindesine was tested with the MTT method. Expression of multidrug resistance protein mRNAs (MDR1, MRP1, cMOAT/MRP2, and LRP) was analyzed with reverse transcriptase polymerase chain reaction (RT-PCR). Doxorubicin subcellular distribution in those cells was examined by fluorescence microscopy. RESULTS: S1TcTax05 and S1TcTax10 showed resistance to doxorubicin, etoposide, and vindesine, but not to cisplatin as compared with S1T or S1Tneo. RT-PCR demonstrated that MRP1 mRNA was expressed, but MDR1, cMOAT, and LRP mRNAs were not in S1T or S1Tneo. Marked expression of LRP mRNA was detected, but no change of MDR1, MRP1, or cMOAT mRNA expression in Tax-expressing S1TcTax05 and S1TcTax10. Fluorescence microscopy demonstrated that doxorubicin was distributed mainly in the cytoplasm of S1TcTax05 and S1TcTax10, and in the nucleus of S1T and S1Tneo. CONCLUSIONS: These findings suggest that Tax-related drug resistance of ATL cells is due to LRP and not MDR1, as reported previously. These findings in cells derived from an ATL patient suggest a novel mechanism for drug resistance in Tax-expressing ATL cells.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2003

Aberrant processing of Fas transcripts in adult T-cell leukemia: a possible role in tumor cell survival.

In adult T-cell leukemia (ATL), tumor cells commonly express abundant membrane-bound Fas antigen. We reported a significant correlation between Fas expression status of ATL patients and their clinical outcome. In the current study, we analyzed the Fas cDNA sequence of the distinctive ATL cases that barely expressed mFas identified during the previous study. According to the results, changes in the Fas amino acid sequence were deduced in two of seven cases. Furthermore, we identified seven novel variants of Fas mRNA produced by alternative splicing. Our data indicates the diversity of Fas gene expression at a mRNA level in ATL.

Alternative Splicing↗
PubMed2002

Canine infection and the possible role of dogs in the transmission of American tegumentary leishmaniosis in Salta, Argentina.

Some Leishmania species affect humans in two principal forms: visceral and cutaneous leishmaniosis (CL). Several studies have identified dogs as the main reservoirs of the visceral leishmaniosis (VL) caused by Leishmania infantum. The purpose of this work was to carry out a survey of the canine population associated with human cases of American tegumentary leishmaniosis (ATL), in order to establish the clinical, parasitological, serological and immunological characteristics of the canine disease, in an endemic region for both ATL and Chagas' disease in the province of Salta, in northwestern Argentina. Two hundred and eight dogs from the endemic area were examined and 41 (19.7%) of them presented lesions compatible with leishmaniosis. In order to investigate the presence of antibodies against Leishmania spp. and Trypanosoma cruzi, sera were screened by ELISA using two complex antigens from these parasites and, because of cross-reactions between them, a specific antigen for diagnosis of T. cruzi infection. Sixty-two (29.8%) of 208 dogs were positive for the complex antigen F45 from Leishmania and 50 (24%) were positive for the complex antigen F105 from T. cruzi. Nine dogs (4.3%) were positive for the specific Ag163B6-cruzipain suggesting that these dogs were truly infected with T. cruzi. Furthermore, three of these nine dogs presented Leishmania sp. in their skin lesions and therefore were considered as infected by both, T. cruzi and Leishmania parasites. The prevalence of Leishmania infection detected by lesions and/or positive serology was 27.4% (57/208). On the basis of previous observations regarding the clustered appearance of human ATL, the dog population was divided into two groups: zone A, dogs living within a 100 m radius from houses with human cases, and zone B, dogs living beyond this limit. The prevalence of ATL in dogs was significantly higher in zone A (34.6%) than in zone B (7.3%), suggesting a strong correlation between canine and human cases. The average time required for a parasitological diagnosis by microscopy was six times longer for dog samples than human ones, and the average number of parasites per 100 microscopic fields was 14-fold lower in canine samples. The high prevalence of Leishmania infection and the close association with human cases, demonstrated that dogs are a very susceptible host for Leishmania infection, but the scarcity of parasites in their lesions suggests that they may not be the main reservoir of the parasite in this endemic area.

Animals↗
PubMed2000

Simultaneous determination of atenolol and amlodipine in tablets by high-performance thin-layer chromatography.

A new simple, precise, rapid and selective high-performance thin-layer chromatographic (HPTLC) method has been developed for the simultaneous determination of atenolol (ATL) and amlodipine (AMLO) in tablets, using methylene chloride:methanol:ammonia solution (25% NH3) (8.8:1.3:0.1; v/v) as the mobile phase and Merck HPTLC plates (0.2 mm thickness) precoated with 60F254 silica gel on aluminium sheet as the stationary phase. Detection was carried out densitometrically using a UV detector at 230 nm. The retention factors of ATL and AMLO were 0.33 and 0.75, respectively. Calibration curves were linear in the range 10-500 microg ml(-1) for both. Assays of ATL and AMLO were 49.87 mg per tablet (relative standard deviation (R.S.D.), 1.3%) and 4.90 mg per tablet (R.S.D., 1.38%) for brand I, and 49.27 mg per tablet (R.S.D., 1.12%) and 4.98 mg per tablet (R.S.D., 1.42%) for brand II, respectively. The percentage recoveries for ATL and AMLO for brands I and II were 99.06 and 99.30%, and 99.27 and 99.15%, respectively.

Amlodipine↗
PubMed1997

Assessing changes over time in temporal lobectomy: outcome by scoring seizure frequency.

Current methods of evaluating seizure outcome after anterior temporal lobectomy (ATL) have major limitations. We evaluated the usefulness of a recently proposed system in our study of the stability of seizure frequency after ATL in 184 patients with intractable epilepsy. Data collection by chart review was supplemented by an intensive program of follow-up by our survey research center through correspondence or phone calls according to a protocol approved by our Institutional Review Board. Seizure frequency during each 12-month period after ATL was scored for each patient. The only statistically significant change in seizure frequency scores during follow-up was between the third and the fourth years (means of 2.61 and 2.11; P < 0.045). Further assessment showed that the change was most likely due to an increase in the proportion of patients who achieved a score of 0 when they successfully stopped taking antiepileptic medications (9.1% in the third year and 22.5% in the fourth year; P < 0.05). There was no statistically significant difference between follow-up years in the proportion of patients achieving excellent outcome (i.e. scores of 0-4). Outcome remained unchanged when follow-up at each year was confined to the same patients throughout their postsurgical course. By using the Seizure Frequency Scoring System, we have demonstrated that seizure outcome remains stable after ATL. The scoring system facilitates the detection of subtle changes in the postoperative course. The advantages and the limitations of the system are discussed.

Adult↗
PubMed2003

Emotional facial paresis in temporal lobe epilepsy: its prevalence and lateralizing value.

The selection of patients with medically refractory temporal lobe epilepsy (TLE) for surgery depends on the concordance of data from clinical, imaging and electroencephalographic evaluation. Though clinical examination is often normal, emotional facial paresis has been described in patients with TLE. Utilizing a well-characterized group of mesial TLE (MTLE) patients, who have achieved excellent seizure outcome following anterior temporal lobectomy with amygdalohippocampectomy (ATL), we investigated the prevalence, predictive value and associations of emotional facial paresis. When compared to 8 out of 50 control subjects (16%), 36 out of 50 MTLE patients (72%) exhibited unilateral emotional facial paresis; the difference was highly significant (P<0.0001). The presence of contralateral emotional facial paresis correctly predicted the side of ATL in 86.1% patients. The occurrence of emotional facial paresis was significantly associated with longer duration of epilepsy prior to ATL and left ATL. Our observations confirm that emotional facial parersis contralateral to the side of mesial temporal sclerosis (MTS) is a valuable localizing sign in correctly predicting the epileptogenic temporal lobe. We hypothesize that the presence of an intact right hemisphere and pathological changes more extensive than MTS may be required for emotional facial paresis to readily manifest.

Adolescent↗
PubMed2002

Predictors of postoperative memory function after left anterior temporal lobectomy.

Patients who undergo left anterior temporal lobectomy (ATL) for intractable epilepsy are at risk of postoperative memory decline. This study attempts to identify the best predictors of memory after ATL using preoperative tests. Thirty-two consecutive patients who underwent left ATL with preoperative and postoperative neuropsychological testing were retrospectively identified. The following independent variables were analyzed by multiple regression: age of onset of seizures, age of temporal lobe damage, gender, MRI results, preoperative memory testing, and intracarotid amytal procedure (IAP) results. Neuropsychological measures of verbal and nonverbal memory served as dependent variables. Male gender (P<0.005), failing the IAP with both left and right hemispheres (P<0.001), and higher logical memory (LM) scores preoperatively (P<0.001) were associated with greater declines in LM after surgery. Our data demonstrate that the IAP predicts postoperative memory independent of other factors known to affect memory after left ATL.

Journal Article↗
PubMed2005

The acquisition of face and person identity information following anterior temporal lobectomy.

Thirty unilateral anterior temporal lobectomy (ATL) subjects (15 right and 15 left) and 15 controls were presented a multitrial learning task in which unfamiliar faces were paired with biographical information (occupation, city location, and a person's name). Face recognition hits were similar between groups, but the right ATL group committed more false-positive errors to face foils. Both left and right ATL groups were impaired relative to controls in acquiring biographical information, but the deficit was more pronounced for the left ATL group. Recall levels also varied for the different types of biographical information; occupation was most commonly recalled followed by city name and person name. In addition, city and person name recall was more likely when occupation was also recalled. Overall, recall of biographical information was positively correlated with clinical measures of anterograde episodic memory. Findings are discussed in terms of the role of the temporal lobe and associative learning ability in the successful acquisition of new face semantic (biographical) representations.

Adult↗
PubMed2005

Insecticidal activity of Arum maculatum tuber lectin and its binding to the glycosylated insect gut receptors.

Mannose binding approximately 50 kDa homotetrameric lectin, purified from edible Arum maculatum tuber, was analyzed through SDS-PAGE and studied for its agglutination property using rabbit erythrocytes. Cross reactivity of the purified lectin was verified through western blot using Colocasia esculantum(Family, Araceae) tuber lectin antibody. The insecticidal activity of Arum maculatum tuber lectin (ATL) was tested against two economically important sucking pests, Lipaphis erysimi and Aphis craccivora, in an artificial diet. The LC(50) values for L. erysimi and A. craccivora were determined to be 21 microg/mL and 16 microg/mL, respectively. Addition of alpha-d-mannose in ATL-supplemented diet reduced the aphid mortality. Two major receptor proteins of ATL (approximately 40 kDa and approximately 35 kDa) were detected from the brush border membrane vesicle (BBMV) protein of L. erysimi and A. craccivora guts, respectively, using ligand-binding assay. Alpha-d-Mannose was found to be a deterrent to such binding of ATL to the BBMV receptors.

Animals↗
PubMed2002

A nested case-control study of risk factors for adult T-cell leukemia/lymphoma among human T-cell lymphotropic virus type-I carriers in Japan.

OBJECTIVES: The purpose of this study was to investigate the serological risk factors for development of adult T-cell leukemia/lymphoma (ATL) among human T-cell lymphotropic virus type-I (HTLV-I) carriers. METHODS: A nested case-control study was performed. The source population comprised 23,922 subjects who had either visited the outpatient clinic or who had received annual health check-ups at the K Hospital, Nagasaki, Japan, at least once during 1985-1996 (HTLV-I seroprevalence = 16.1%). Markers of HTLV-I infection were examined in stored sera from 29 incident cases of ATL diagnosed during 1985-1997, and 158 controls matched for sex, birth year, date of sample collection, and HTLV-I seropositivity (median follow-up = 6.4 years). RESULTS: In exact conditional logistic regression analysis, high levels of soluble interleukin-2 receptor (> or = 500 U/ml) and high HTLV-I antibody titers (> or = 1,024) were independently associated with an increased risk of developing ATL (Odds ratio 20.5. 95% confidence interval (CI) 4.5-194 and 2.9, 95% CI 0.98-9.5, respectively). The results remained essentially unchanged when the subjects were restricted to those whose histories were followed for two years or longer. CONCLUSIONS: These findings indicate that high soluble interleukin-2 receptor levels and high HTLV-I antibody titers are strong predictors of ATL among carriers of HTLV-I.

Age Distribution↗
PubMed2003

Human T-lymphotropic virus type-I infection, survival and cancer risk in southwestern Japan: a prospective cohort study.

OBJECTIVES: This study prospectively evaluated the associations of human T-lymphotropic virus type-I (HTLV-I) infection with survival and cancer incidence. METHODS: The study base comprised 4297 adults (aged 40-69 years in 1993) who had either visited the outpatient clinic or who had received annual health check-ups at the A Hospital, Nagasaki, Japan, between 1985 and 1992 (HTLV-I seropositivity = 24.7%). During the follow-up period (1993-1999 or 2000), 290 deaths and 261 cases of malignant neoplasms occurred, including ten deaths and six incident cases of adult T-cell leukemia/lymphoma (ATL). RESULTS: After adjustment for gender, age and other covariates, HTLV-I seropositivity was associated with an increased mortality from all-causes excluding ATL (rate ratio, RR = 1.3, 95% confidence interval, CI = 1.0-1.7), all non-neoplastic diseases (RR = 1.5, 95% CI = 1.0-2.3) and heart diseases. HTLV-I infection was not found to be associated with an increased risk of developing total cancers other than ATL (RR = 0.98, 95% CI = 0.74-1.3), colorectal cancers, liver cancer or lung cancer, but was associated with a reduced risk of gastric cancer (RR = 0.42, 95% CI = 0.17-0.99). CONCLUSIONS: HTLV-I infection is associated with increased mortality from all-causes excluding ATL and all non-neoplastic diseases. HTLV-I carriers may not be at increased general cancer risk, but at reduced risk of gastric cancer.

Aged↗
PubMed1994

Declarative memory following anterior temporal lobectomy in humans.

This study hypothesized that verbal memory decline following anterior temporal lobectomy (ATL) is associated with a lack of significant neuropathology in resected left, but not right, hippocampus and is limited to measures of episodic memory only. Tests of immediate (digit span), semantic (visual naming), and episodic memory as measured by the California Verbal Learning Test (CVLT) were administered before and 6 months after resection of the anterior left (n = 36) or right (n = 26) temporal lobe. There were no effects of hippocampal pathology on measures of immediate or semantic memory for either ATL group or for episodic memory for the right ATL group. Left ATL patients who demonstrated no/mild hippocampal sclerosis exhibited significantly greater postoperative decline in episodic memory compared with those with moderate/marked hippocampal sclerosis on multiple CVLT indices (recall measures, learning characteristics, and contrast measures).

Adult↗
PubMed2006

Lateralization of the startle reflex circuit in humans: an examination with monaural probes following unilateral temporal lobe resection.

Startle reflex (SR) modulation elicited by monaural probes during affective picture viewing was investigated in patients following left temporal lobectomy (LTL; n = 8) and right temporal lobectomy (RTL; n = 10) and in controls (n = 18). All patients had undergone anteromedial temporal lobe (ATL) resection. LTL participants exhibited attenuated overall SR magnitude. Affective SR modulation in controls was significant for left ear probes, at both eyes, but not for right ear probes. RTL but not LTL participants displayed significant startle attenuation during pleasant picture viewing. Results suggest that monaural startle probes primarily activate structures in the ipsilateral ATL and that the ATLs are interconnected, with the left ATL more critical in perceiving arousing properties of affective stimuli, necessary for affective SR modulation.

Adult↗
PubMed1994

Treatment of adult T-cell leukaemia-lymphoma with irinotecan hydrochloride (CPT-11). CPT-11 Study Group on Hematological Malignancy.

A late phase II study of a new camptothecin analogue, irinotecan hydrochloride (CPT-11), was conducted to evaluate the anti-tumour effect and toxicity in patients with refractory leukaemia and lymphoma including adult T-cell leukaemia (ATL)-lymphoma, in a multi-institutional cooperative study. All the patients with ATL had been previously treated with various conventional combination chemotherapies and were refractory to these therapies or had relapsed. CPT-11 was administered at a dose of 40 mg m-2 day-1 for three consecutive days repeated weekly until evidence of disease progression. One complete remission and four partial remissions were achieved in 13 assessable patients with ATL. The median total dose to achieve remission was 240 mg m-2 and the median duration of response was 31 days. The major toxicities were leucopenia (83%), diarrhoea (62%) and nausea/vomiting (69%). These were relatively severe, but they were generally tolerable and reversible. However, one patient died probably as a result of this therapy. No effective chemotherapy for adult T-cell leukaemia-lymphoma has yet been established, and the prognosis for patients with this disease is very poor. Our results suggest that CPT-11 may be a promising agent for this disease. Further combination therapy with CPT-11 is needed to improve the therapy for ATL.

Adult↗
PubMed2001

Improved outcome of adult T cell leukemia/lymphoma with allogeneic hematopoietic stem cell transplantation.

Adult T cell leukemia/lymphoma (ATL) is a poor prognosis T cell malignancy. In order to improve the outcome, we employed allogeneic stem cell transplantation (allo-SCT) for ATL in 10 patients, nine of whom were from HLA-identical siblings and one from an unrelated donor. Conditioning regimens varied among the patients except that all received total body irradiation. The patients tolerated the regimens well with mild, if any toxicity, and engraftment occurred in all cases. Median leukemia-free survival after allo-SCT was 17.5+ months (range 3.7-34.4+). Six of the 10 patients developed acute GVHD (one case each with grade I, III or IV, and three cases with grade II) and three patients developed extensive chronic GVHD. Four patients died after allo-SCT during the study period from either acute GVHD (grade IV), pneumonitis, gastrointestinal bleeding or renal insufficiency. Two of the 10 cases with no symptoms of GVHD relapsed with clinical ATL. These results strongly suggest that allo-SCT may improve the survival in ATL if a controlled degree of GVHD develops.

Adult↗
PubMed1998

A novel single cell PCR assay: detection of human T lymphotropic virus type I DNA in lymphocytes of patients with adult T cell leukemia.

The abnormal lymphocytes in adult T cell leukemia (ATL) reveal a peculiar morphology that is characterized by indented or lobulated nuclei. While human T lymphotropic virus type I (HTLV-I) is thought to be integrated in ATL cells, the correlation between the nuclear irregularities and HTLV-I infection is obscure. We have devised a novel single cell polymerase chain reaction (PCR) technique to examine the integration of HTLV-I provirus genome in cells from two patients with ATL. To isolate single cells, peripheral blood smears were prepared on thin polyester slides and stained with May-Grünwald-Giemsa. Morphologically defined single cells were cut out after light microscopy. The HTLV-I DNA sequences were detected not only in ATL cells but also in normal-looking lymphocytes. This novel PCR method may provide a valuable tool for understanding the molecular events associated with HTLV-I infection at the single cell level.

Adult↗
PubMed2005

Discrete serum protein signatures discriminate between human retrovirus-associated hematologic and neurologic disease.

The human T-cell leukemia virus type I (HTLV-I) is the causative agent for adult T-cell leukemia (ATL) and HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP). Approximately 5% of infected individuals will develop either disease and currently there are no diagnostic tools for early detection or accurate assessment of disease state. We have employed high-throughput expression profiling of serum proteins using mass spectrometry to identify protein expression patterns that can discern between disease states of HTLV-I-infected individuals. Our study group consisted of 42 ATL, 50 HAM/TSP, and 38 normal controls. Spectral peaks corresponding to peptide ions were generated from MS-TOF data. We applied Classification and Regression Tree analysis to build a decision algorithm, which achieved 77% correct classification rate across the three groups. A second cohort of 10 ATL, 10 HAM and 10 control samples was used to validate this result. Linear discriminate analysis was performed to verify and visualize class separation. Affinity and sizing chromatography coupled with tandem mass spectrometry was used to identify three peaks specifically overexpressed in ATL: an 11.7 kDa fragment of alpha trypsin inhibitor, and two contiguous fragments (19.9 and 11.9 kDa) of haproglobin-2. To the best of our knowledge, this is the first application of protein profiling to distinguish between two disease states resulting from a single infectious agent.

Adolescent↗
PubMed2005

Transcriptional regulation of parathyroid hormone-related protein promoter P3 by ETS-1 in adult T-cell leukemia/lymphoma.

Parathyroid hormone-related protein (PTHrP) plays a primary role in the development of humoral hypercalcemia of malignancy seen in the majority of adult T-cell leukemia/lymphoma (ATLL) patients with human T-cell lymphotropic virus type-1 (HTLV-1) infection. HTLV-1 Tax has been shown to complex with ETS-1 and SP1 to transactivate the PTHrP P3 promoter. Previously, we established a SCID/bg mouse model of human ATL with RV-ATL cells and showed that PTHrP expression was independent of Tax. In this study, we report an inverse correlation of PTHrP with tax/rex mRNA in multiple HTLV-1-positive cell lines and RV-ATL cells. Stimulation of Jurkat T cells with PMA/ionomycin upregulated the PTHrP P3 promoter by a previously characterized Ets binding site and also induced protein/DNA complex formation identical to that observed in RV-ATL cells. Further, we provide evidence that cotransfection with Ets-1 and constitutively active Mek-1 in HTLV-1-negative transformed T cells with stimulation by PMA/ionomycin not only resulted in a robust induction of PTHrP P3 but also formed a complex with ETS-1/P3 EBS similar to that in ATLL cells. Our data demonstrate that transcriptional regulation of PTHrP in ATLL cells can be controlled by T-cell receptor signaling and the ETS and MAPK ERK pathway in a Tax-independent manner.

Adult↗