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PubMed1990

Cytogenetic studies of human T-cell leukemia virus type I carriers. A family study.

Recently, the chromosome 14q11 anomaly has been reported to be specific to adult T-cell leukemia (ATL), and this anomaly has also been confirmed in the preleukemic state of adult T-cell leukemia (pre-ATL) patients. Because the cytogenetic abnormality at the stage of human T-cell leukemia virus type I (HTLV-I) carrier remains uncertain, we performed cytogenetic studies of lymphocytes stimulated with phytohemagglutinin in three HTLV-I carriers and three non-HTLV-I carriers in an ATL family. As a result, in three HTLV-I carriers, four of 311 cells examined (1.3%) had chromosome 14q11 anomaly. However, in three non-HTLV-I carriers, none of 260 cells examined had chromosome 14q11 anomaly. These results suggest that chromosome 14q11 anomaly is already present at the stage of HTLV-I carrier and seems to be an important cytogenetic clue to the pathogenesis of ATL.

Adult↗

PubMed1996

[Strongyloides stercoralis in T-cell leukemia/lymphoma in adults and acquired immunodeficiency syndrome].

The mechanisms of chronic infestation by Strongyloides stercoralis (Ss) are unknown. Immunodepression is classically evoked to explain the proliferation of the parasite that is sometimes massive and overwhelming. We present here two retrospective studies of 13 cases of strongyloidiasis (three disseminated strongyloidiasis) out of 26 patients with adult T-cell leukemia/lymphoma (ATL) and of ten cases of strongyloidiasis out of 98 patients with AIDS. Ten patients out of 98 were dually infected with both HIV and HTLV-1: 2/10 also infected by Ss. The frequency of Ss infection appears higher in ATL patients when compared with AIDS patients (P < 0.001). Ss-infected ATL patients were younger than those uninfected (P < 0.01). Ss-infected AIDS patients were older than the ones uninfected (p < 0.03). No significative difference was found between ATL and AIDS patients who were over 40 years-old. These data suggest that 1) the particular type of immunodepression produced early by HTLV-1 is more favorable to the development of Ss infection than the one associated with HIV, 2) the latency of expression of HTLV-1, prior to the development of leukemia, is reduced in Ss-infected patients, 3) Ss infection may slow down VIH pathogenic activity.

AIDS-Related Opportunistic Infections↗

PubMed1984

The relationship of the level of training and area of medical specialization with registrant performance in an advanced trauma life-support course.

Approved advanced trauma life-support (ATLS) programs were given to 160 residents and practitioners of various specialties, utilizing a standardized 50-item, multiple-choice posttest. Level of training (practitioner v resident) and area of medical specialization with registrant performance on total score and in specific subcontent areas of ATLS were evaluated by subjecting total and subcontent percent scores to a two-way analysis of variance and Newman-Keuls pairwise comparisons. Practitioners outperformed the residents in the subcontent area of abdominal injuries, P less than .05. In specialization, emergency medicine outperformed internal medicine specialists, P less than .05. Pairwise differences among specialists were not statistically significant. In airway problems, surgeons and internists were outperformed by emergency medicine, whereas in burns, emergency medicine and family practitioners significantly outperformed the surgeons. Emergency medicine outperformed internal medicine, P less than .05, in subcontent area of extremity injuries. We conclude that registrants are likely to benefit from an ATLS course, but preliminary evidence would seem to justify some "tailoring" of the ATLS curriculum for different registrant specialty groups.

Curriculum↗

PubMed2006

Hypergammaglobulinemia and corneal opacities in patients with human T-cell lymphotrophic virus type-1.

PURPOSE: To investigate the relationship between serum immunoglobulin levels and corneal opacities in a cohort of patients with human T-cell lymphotrophic virus type-1 (HTLV-1). DESIGN: Retrospective case series. METHODS: Complete ophthalmologic examination was performed on 44 patients with HTLV-1 infection (25 patients with adult T-cell leukemia/lymphoma [ATL], 18 patients with HTLV-1 that was associated myelopathy/tropical spastic paraparesis [HAM/TSP], and one patient who was asymptomatic). Corneal opacities were described by shape, size, color, and location. Serum immunoglobulin (Ig) levels (IgG, IgM, and IgA) were measured by nephelometry. RESULTS: Corneal opacities were identified in 15 of 25 patients (60%) with ATL and five of 18 patients (28%) with HAM/TSP. The prevalence of corneal opacities was associated statistically with elevated IgG level (P = .023) in patients with ATL, but not in patients with HAM/TSP (P > .99). CONCLUSION: Although the mechanism remains unclear, hypergammaglobulinemia is associated with the development of the corneal opacities in patients of African descent with ATL.

Corneal Opacity↗

PubMedDate not supplied

A case of uveal, palpebral, and orbital invasions in adult T-Cell leukemia.

BACKGROUND: Patients with adult T-cell leukemia (ATL) may have eyelid lymphoma, uveitis, or cytomegalovirus retinitis due to being immunocompromised. However, there have been few reports on the invasion of multiple ocular lesions. We treated 1 unusual ATL patient with uveitis in whom multiple ocular invasions were suspected. CASE: A woman in whom ATL was diagnosed 10 years previously complained of blurred vision and decreased visual acuity in the right eye. Anterior uveitis of the right eye was suspected. One week later the cells increased in the anterior chamber, and fibrin exudates and hyphema appeared. She was admitted to our hospital. OBSERVATIONS: The visual acuity was 0.04 in the right eye and finger-counting from 30 cm in the left. She was treated with systemic steroid therapy. Inflammation disappeared, but both eyelids became swollen and multiple ocular lesions appeared. She was given carcinostatic therapy once more and the mass lesions decreased. Mass lesions appeared in the iris and in the bulbar conjunctiva. Computed tomography and magnetic resonance imagining (MRI) showed that the mass lesions extended to the right orbit and both nasal cavities. MRI also demonstrated choroidal thickening in the left eye. CONCLUSION: This case documents that ATL cells may cause severe uveitis and invade multiple ocular tissues such as the iris, eyelid, choroids, and orbit.

Adult↗

PubMed2005

Curcumin suppresses constitutive activation of AP-1 by downregulation of JunD protein in HTLV-1-infected T-cell lines.

Activation of the activator protein 1 (AP-1) plays a critical role in oncogenesis by human T-cell leukemia virus type 1 (HTLV-1), the etiologic agent of adult T-cell leukemia (ATL), and is required for maintenance of the malignant phenotype. Curcumin (diferuloylmethane), the major pigment of the spice turmeric, has anti-tumor activity; however, the effect of curcumin against ATL has not been elucidated. In this study, we examined the effects of curcumin on AP-1 activity in HTLV-1-infected T-cell lines. Curcumin suppressed the constitutive AP-1 DNA-binding and transcriptional activity in HTLV-1-infected T-cell line. Curcumin also inhibited HTLV-1 Tax-induced AP-1 transcriptional activity. JunD was detectable as a major component of the AP-1-DNA complex in HTLV-1-infected T-cell lines using the supershift assay. The expression of JunD was suppressed by curcumin treatment. Curcumin inhibited the growth of HTLV-1-infected T-cell lines by inducing cell cycle arrest followed by apoptosis. Our results suggest that suppression of the constitutively active AP-1 by curcumin is due to, at least in-part, reducing the expression of JunD by curcumin. Inhibition of AP-1 activity by curcumin may be one of the mechanisms responsible for the anti-ATL effect of curcumin. We propose that curcumin is a potentially promising compound for the treatment of ATL.

Apoptosis↗

PubMed2006

Multidrug resistance protein expression of adult T-cell leukemia/lymphoma.

In adult T-cell leukemia/lymphoma (ATL), it is difficult to achieve remission and the reason for the resistance to chemotherapeutic agents may be linked to the presence of multidrug resistance (MDR) proteins. Lung resistance-related protein (LRP), multidrug resistance-associated protein and P-glycoprotein are three MDR proteins which we examined in ATL cells using multiparametric flow cytometry and real-time RT-PCR. LRP was highly expressed and suppressing LRP function increased doxorubicin accumulation in nuclei. This indicates LRP may be contributing to drug resistance in ATL patients, and the suppression of LRP function could be a new strategy for ATL treatment.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed2006

Loss of spastic paraplegia gene atlastin induces age-dependent death of dopaminergic neurons in Drosophila.

Hereditary spastic paraplegias (HSPs) are human genetic disorders causing increased stiffness and overactive muscle reflexes in the lower extremities. atlastin (atl) is one of the major genes in which mutations result in HSP. We generated a Drosophila model of HSP that has a null mutation in atl. As they aged, atl null flies were paralyzed by mechanical shock such as bumping or vortexing. Furthermore, the flies showed age-dependent degeneration of dopaminergic neurons. These phenotypes were rescued by targeted expression of atl in dopaminergic neurons or feeding L-DOPA or SK&F 38393, an agonist of dopamine receptor. Our data raised the possibility that one of the causes of HSP disease symptoms in human patients with alt mutations is malfunction or degeneration of dopaminergic neurons.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗

PubMedDate not supplied

Anti-inflammatory circuitry: lipoxin, aspirin-triggered lipoxins and their receptor ALX.

Endogenous chemical mediators or autacoids play key roles in controlling inflammation and its programmed resolution. Among them, it is known that lipoxins (LX) and aspirin-triggered LX (ATL) evoke bioactions in a range of physiologic and pathophysiologic processes and serve as endogenous lipid/chemical mediators that stop neutrophilic infiltration and initiate resolution. LXA4, ATL and their metabolic stable analogs elicit cellular responses and regulate PMN in vivo via interacting with their specific receptor, namely ALX. ALX is the first cloned and identified lipoxygenase-derived eicosanoid receptor with cell type-specific signaling pathways. Also, ALX could regulate PMN by interacting with each class of ligands (lipid vs. peptide) within specific phases of an inflammatory response. Together LX, ATL and ALX may provide new opportunities to design "resolution-targeted" therapies with high degree of precision in controlling inflammation. In this chapter, we give an overview and update of the current actions for LX and ATL, the identification of ALX and their novel anti-inflammatory and pro-resolving signals.

Amino Acid Sequence↗

PubMed2004

Immunological risks of adult T-cell leukemia at primary HTLV-I infection.

A small percentage of human T-cell leukemia virus type-I (HTLV-I)-infected individuals develop adult T-cell leukemia (ATL). In animal experiments, inoculation of HTLV-I via the oral route, which is the main route of mother-to-child viral transmission in humans as a result of breastfeeding, induced host HTLV-I-specific T-cell unresponsiveness and resulted in increased viral load. This strongly suggested that the known epidemiological risk factors for ATL (i.e. vertical HTLV-I infection and elevated viral load) are linked by an insufficient HTLV-I-specific T-cell response. Recent findings on the anti-tumor effects of Tax-targeted vaccination in rats and the reactivation of Tax-specific T cells in ATL patients as a result of hematopoietic stem cell transplantation imply promising immunological approaches for the prophylaxis and therapy of ATL.

Animals↗

PubMed2006

Comparison of neuropsychological outcomes after selective amygdalohippocampectomy versus anterior temporal lobectomy.

Transsylvian selective amygdalohippocampectomy (TSA) is an operative technique designed to spare unaffected brain tissue during surgical treatment for mesial temporal lobe epilepsy. In contrast to standard anterior temporal lobectomy (ATL), the advantages of TSA with respect to postoperative cognitive outcome are equivocal. We compared cognitive function before and after surgery in 49 patients with unilateral mesial temporal lobe seizures who underwent either ATL (n=17) or TSA (n=32). All patients received neuropsychological testing before and 1 year after surgery. The intelligence quotient (IQ) increased postoperatively in both surgical groups. Memory evaluation in the ATL group revealed a postoperative decline in nonverbal memory after right-sided resection and a postoperative decline in verbal memory after left-sided resection. In the TSA group, there was a slight postoperative decline only in verbal memory after left-sided resection, but other memory function was well preserved. In particular, there was significant postoperative improvement in verbal memory after right-sided resection. Overall, memory function was better preserved in the TSA group than in the ATL group.

Adult↗

PubMed2002

Intraocular infiltration of adult T-cell leukemia.

PURPOSE: To report a case of adult T-cell leukemia (ATL) with unilateral dense vitreous opacities that benefited from vitrectomy. DESIGN: Interventional case report. METHODS: Diagnostic vitrectomy was performed on a 59-year-old man with ATL who had vitreous opacity in the right eye. RESULTS: White infiltration of the retina was noted after vitrectomy. Cytologic examination of the vitreous specimen obtained during surgery revealed infiltration of ATL cells into the vitreous and retina. After vitrectomy and additional chemotherapy, visual acuity improved in the right eye from 20/100 to 25/20. CONCLUSION: Infiltration of the vitreous and retina by ATL is rare. Diagnostic vitrectomy is effective for treatment and visual improvement.

Drug Therapy↗

PubMed2001

Selectivity of recombinant human leukotriene D(4), leukotriene B(4), and lipoxin A(4) receptors with aspirin-triggered 15-epi-LXA(4) and regulation of vascular and inflammatory responses.

Aspirin-triggered lipoxin A(4) (ATL, 15-epi-LXA(4)) and leukotriene D(4) (LTD(4)) possess opposing vascular actions mediated via receptors distinct from the LXA(4) receptor (ALX) that is involved in leukocyte trafficking. Here, we identified these receptors by nucleotide sequencing and demonstrate that LTD(4) receptor (CysLT(1)) is induced in human vascular endothelia by interleukin-1beta. Recombinant CysLT(1) receptor gave stereospecific binding with both [(3)H]-LTD(4) and a novel labeled mimetic of ATL ([(3)H]-ATLa) that was displaced with LTD(4) and ATLa ( approximately IC(50) 0.2 to 0.9 nmol/L), but not with a bioinactive ATL isomer. The clinically used CysLT(1) receptor antagonist, Singulair, showed a lower rank order for competition with [(3)H]-ATLa (IC(50) approximately 8.3 nmol/L). In contrast, LTD(4) was an ineffective competitive ligand for recombinant ALX receptor with [(3)H]-ATLa, and ATLa did not compete for [(3)H]-LTB(4) binding with recombinant LTB(4) receptor. Endogenous murine CysLT(1) receptors also gave specific [(3)H]-ATLa binding that was displaced with essentially equal affinity by LTD(4) or ATLa. Systemic ATLa proved to be a potent inhibitor (>50%) of CysLT(1)-mediated vascular leakage in murine skin (200 microg/kg) in addition to its ability to block polymorphonuclear leukocyte recruitment to dorsal air pouch (4 microg/kg). These results indicate that ATL and LTD(4) bind and compete with equal affinity at CysLT(1), providing a molecular basis for aspirin-triggered LXs serving as a local damper of both vascular CysLT(1) signals as well as ALX receptor-regulated polymorphonuclear leukocyte traffic.

Animals↗

PubMed1996

The effects of human hippocampal resection on the serial position curve.

The purpose of this study was to examine the contribution of the human hippocampal formation to the classic serial position curve. Seventy-seven patients who underwent anterior temporal lobectomy (ATL) (47 left, 30 right) were administered a list learning task before and after surgery, and changes in the serial position curve were examined. Forty nonsurgical patients with complex partial seizures were tested at comparable intervals and served as controls. Changes in the serial position curve were seen only after left ATL, and almost exclusively among patients without hippocampal sclerosis. Patients without left hippocampal sclerosis, and who therefore underwent resection of hippocampus that was to a considerable degree structurally (and presumably functionally) intact, showed significant declines in recall from the primacy and middle portions of the list compared to all other groups. There was no change in the recency portion of the list. Patients with left hippocampal sclerosis showed only a modest decline in recall from the middle region compared only to the control group, and the right ATL groups did not show any significant changes in serial position recall. These findings demonstrate the contribution of the left hippocampus to those discrete portions of the serial position curve which rely on secondary memory, and have implications for assessing the effects of ATL on memory function.

Adult↗

PubMed2000

Confrontation naming after anterior temporal lobectomy is related to age of acquisition of the object names.

Decline in visual confrontation naming ability may occur as a postacute complication of left anterior temporal lobectomy (ATL) for the treatment of intractable mesial temporal lobe epilepsy. In this study of 26 left ATL patients who demonstrated postsurgery decline on a standardized naming measure, it was hypothesized that naming performance would be significantly associated with specific attributes of the object names. We investigated the relation between performance on the Boston Naming Test (BNT) and the following attributes of the test items: living versus nonliving category (L/NL), word length (WL), written word frequency (WF), and age of acquisition (AoA). Regression analyses revealed that AoA and WF were significant predictors of preoperative group performance. AoA was the only significant predictor of performance after left ATL. For the 17 individuals who demonstrated a statistically meaningful decline on the BNT, as indicated by a Reliable Change Index, individual logistic regressions demonstrated that AoA was the strongest and most consistent predictor of postoperative success/failure for items that had been named correctly preoperatively. Consistent with the literature on naming errors in elderly normals and patients with aphasia or semantic dementia, the results provide evidence that object names learned in late childhood are among the most vulnerable when there is a decline in object naming ability. Investigation of additional attributes and semantic knowledge for the concepts represented by the pictured objects will be necessary to determine whether the naming deficit associated with TLE and ATL reflects an impairment of phonological word-form retrieval, semantics, or both.

Adult↗

PubMed2003

Capsaicin inhibits growth of adult T-cell leukemia cells.

Human T-cell leukemia virus type 1 (HTLV-1)-associated adult T-cell leukemia (ATL) is resistant to conventional chemotherapy. We examined the in vitro effects of capsaicin, the principal ingredients of red pepper, on three ATL cell lines. Capsaicin treatment inhibited the growth of ATL cells both in dose- and time-dependent manner. The inhibitory effect was mainly due to the induction of cell cycle arrest and apoptosis. Capsaicin treatment also induced the degradation of Tax and up-regulation of I kappa-B alpha, resulting in the decrease of nuclear factor (NF)-kappa B/p65 DNA binding activity. In addition, the Bcl-2 level was found to be decreased. Based on these findings, capsaicin may be considered for chemoprevention of ATL.

Apoptosis↗

PubMed1985

Cutaneous manifestations of adult T cell leukemia/lymphoma. Report of three different forms.

The clinical and pathologic features of cutaneous lesions observed in three adult T cell leukemia/lymphoma (ATL) patients identified in Taiwan are described. They represent one classical case of ATL and two "smoldering" variants. The classical ATL patient when first seen had numerous erythematous or purpuric papules, nodules, and plaques with or without ulceration. The two "smoldering" cases developed encrusted purpuric plaques with subcutaneous erythematous nodules in one patient and pompholyx-like vesicular eruptions with tumor masses in another patient. The pompholyx-like eruptions have not been described before. Pruritus was the major complaint in two patients. Histopathologic studies revealed pleomorphic infiltration in the classical case and monomorphic infiltration with medium-sized cells in the two "smoldering" variants. Therefore, the cutaneous lesions of ATL are diverse and not pathognomonic. The diagnosis requires a high index of suspicion, detection of circulating characteristic multilobated lymphoid cells with T helper/inducer cell marker, and demonstration of serum antibody against the adult T cell leukemia virus-associated antigen.

Adult↗

PubMed1996

Clinical and histologic spectrum of human T-cell lymphotropic virus type I-associated lymphoma involving the skin.

BACKGROUND: Adult T-cell leukemia/lymphoma (ATL) is associated with infection with human T-cell lymphotropic virus type I (HTLV-I). OBJECTIVE: The objective was to describe the clinical, histopathologic, and immunologic features in three patients with ATL involving the skin. METHODS: Clinical histories and skin biopsy specimens were reviewed. Immunophenotypic studies were performed on peripheral blood lymphocytes (three patients) and on skin biopsy specimens (one patient). RESULTS: Serologic testing in each patient was positive for HTLV-I. Specific cutaneous lesions of ATL were diverse. Histologic features included markedly epidermotropic lymphoid infiltrates and dermal aggregates of lymphocytes and macrophages resembling granulomas. One patient died 3 months after diagnosis; the other two are alive with residual lymphoma. CONCLUSION: A spectrum of clinical, histologic, and immunophenotypic features are seen in ATL involving skin. Those cases with a chronic course may resemble mycosis fungoides clinically and histologically. Serologic testing for HTLV-I is recommended in all patients with cutaneous lymphoma from endemic areas and in those with other risk factors for HTLV-I infection.

Adult↗