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At least 991 records · Page 55Linked to original sources
PubMed2003

Real-time PCR assay compared to nested PCR and antigenemia assays for detecting cytomegalovirus reactivation in adult T-cell leukemia-lymphoma patients.

We analyzed the efficiency of the quantitative real-time PCR assay for cytomegalovirus (CMV) reactivation in adult T-cell leukemia-lymphoma (ATL) patients and compared the results with those obtained with qualitative nested PCR and antigenemia assays. The viral load obtained by the real-time PCR assay closely paralleled the number of antigen-positive cells obtained with the antigenemia assay. Real-time PCR revealed that a large number of DNA copies could be present even in samples assessed as negative or low in antigen-positive cells (0 to 10 antigen-positive cells/50,000 cells) by antigenemia assay. CMV copy numbers did not differ between the negative and low-antigen-positive groups. When the input concentration for real-time PCR assay was 2,500 to 5,000 copies/ml, the positivity rate for the nested PCR assay was 47.3%, while the positivity rate was more than 90% at an input concentration of >/=50,000 copies/ml. Real-time PCR is more sensitive than the antigenemia and nested PCR assays. Moreover, real-time PCR was able to detect CMV reactivation earlier than the antigenemia and nested PCR assays through the use of longitudinal analysis in four ATL patients with CMV pneumonia. In longitudinal assessments, analysis of the results suggested that a cutoff level of 5,000 copies/ml might be used to initiate treatment. Real-time PCR is more suitable for monitoring CMV reactivation in ATL patients than the antigenemia and nested PCR assays. CMV viral loads of 5,000 copies/ml are proposed as the cutoff for initiating antiviral therapy in ATL patients.

Adult↗
PubMed2003

Expansion of human T-cell leukemia virus type 1 (HTLV-1) reservoir in orally infected rats: inverse correlation with HTLV-1-specific cellular immune response.

Adult T-cell leukemia (ATL) occurs in a small population of human T-cell leukemia virus type 1 (HTLV-1)-infected individuals. Although the critical risk factor for ATL development is not clear, it has been noted that ATL is incidentally associated with mother-to-child infection, elevated proviral loads, and weakness in HTLV-1-specific T-cell immune responses. In the present study, using a rat system, we investigated the relationships among the following conditions: primary HTLV-1 infection, a persistent HTLV-1 load, and host HTLV-1-specific immunity. We found that the persistent HTLV-1 load in orally infected rats was significantly greater than that in intraperitoneally infected rats. Even after inoculation with only 50 infected cells, a persistent viral load built up to considerable levels in some orally infected rats but not in intraperitoneally infected rats. In contrast, HTLV-1-specific cellular immune responses were markedly impaired in orally infected rats. As a result, a persistent viral load was inversely correlated with levels of virus-specific T-cell responses in these rats. Otherwise very weak HTLV-1-specific cellular immune responses in orally infected rats were markedly augmented after subcutaneous reimmunization with infected syngeneic rat cells. These findings suggest that HTLV-1-specific immune unresponsiveness associated with oral HTLV-1 infection may be a potential risk factor for development of ATL, allowing expansion of the infected cell reservoir in vivo, but could be overcome with immunological strategies.

Administration, Oral↗
PubMed2006

A novel alternative splicing isoform of human T-cell leukemia virus type 1 bZIP factor (HBZ-SI) targets distinct subnuclear localization.

Adult T-cell leukemia (ATL) is associated with prior infection with human T-cell leukemia virus type 1 (HTLV-1); however, the mechanism by which HTLV-1 causes adult T-cell leukemia has not been fully elucidated. Recently, a functional basic leucine zipper (bZIP) protein coded in the minus strand of HTLV-1 genome (HBZ) was identified. We report here a novel isoform of the HTLV-1 bZIP factor (HBZ), HBZ-SI, identified by means of reverse transcription-PCR (RT-PCR) in conjunction with 5' and 3' rapid amplification of cDNA ends (RACE). HBZ-SI is a 206-amino-acid-long protein and is generated by alternative splicing between part of the HBZ gene and a novel exon located in the 3' long terminal repeat of the HTLV-1 genome. Consequently, these isoforms share >95% amino acid sequence identity, and differ only at their N termini, indicating that HBZ-SI is also a functional protein. Duplex RT-PCR and real-time quantitative RT-PCR analyses showed that the mRNAs of these isoforms were expressed at equivalent levels in all ATL cell samples examined. Nonetheless, we found by Western blotting that the HBZ-SI protein was preferentially expressed in some ATL cell lines examined. A key finding was obtained from the subcellular localization analyses of these isoforms. Despite their high sequence similarity, each isoform was targeted to distinguishable subnuclear structures. These data show the presence of a novel isoform of HBZ in ATL cells, and in addition, shed new light on the possibility that each isoform may play a unique role in distinct regions in the cell nucleus.

Alternative Splicing↗
PubMed1990

MR imaging-based volume measurements of the hippocampal formation and anterior temporal lobe: validation studies.

An experiment was designed to compare the accuracy and reproducibility of three different techniques for in vivo magnetic resonance (MR) imaging-based volume measurements of brain structures. These techniques were tracing, thresholding, and random marking. Anterior temporal lobe (ATL) and hippocampal formation (HF) volumes in 10 volunteers were measured from MR images, as were four cylinders of known volume. The upper limit of accuracy of in vivo volume measurements is estimated to be within 0.1 cm3 of true volume for the HF and 0.9 cm3 for the ATL with a combined tracing-thresholding technique. Intra- and interobserver variations were estimated from the pooled standard deviations of HF and ATL measurements. With the combined tracing-thresholding technique, the coefficient of variation for HF measurement was 1.9%; for the ATL measurement, it was 0.7%. The results indicate that MR-based volume measurements of these brain structures can be made with high precision and reproducibility.

Hippocampus↗
PubMed2004

Three-dimensional lateral and vertical relationships of inner medullary loops of Henle and collecting ducts.

Functional reconstruction of inner medullary thin limbs of Henle and collecting ducts (CDs) has enabled us to characterize distinctive three-dimensional vertical and lateral relationships between these segments. We previously reported that inner medullary descending thin limbs (DTLs) that form a bend at a distance greater than approximately 1 mm below the inner medullary base express detectable aquaporin (AQP) 1 only along the initial 40% of the segment before the bend, whereas ClC-K1 is expressed continuously along all ascending thin limbs (ATLs), beginning with the prebend segment. We have now reconstructed individual CDs that are grouped together in single clusters at the base of the inner medulla; CDs belonging to each separate cluster coalesce into a single CD in the deep papilla. DTLs are positioned predominantly at the periphery of each individual CD cluster at all levels of the inner medulla and are absent from within the cluster. In contrast, ATLs are distributed near uniformly among the CDs and DTLs at all levels of the inner medulla. A second population of inner medullary DTLs averages approximately 700 microm in length from base to bend and, as previously reported, expresses no detectable AQP1 and expresses ClC-K1 continuously beginning with the prebend segment. ATLs located within the interior of the CD clusters arise predominantly from these short AQP1-null inner medullary DTLs, suggesting there may be functional interdependence between IMCD1 segments and short-length inner medullary thin limbs exhibiting minimal water permeability along their descending segments. AQP1-expressing DTLs and CDs are apparently separated into two structurally distinct lateral compartments. A similar lateral compartmentation between the ATLs and CDs is not apparent. This architectural arrangement indicates that fluid and solutes may be preferentially transported transversely between multiple inner medullary compartments.

Animals↗
PubMed2005

Three-dimensional architecture of inner medullary vasa recta.

The manner in which vasa recta function and contribute to the concentrating mechanism depends on their three-dimensional relationships to each other and to tubular elements. We have examined the three-dimensional architecture of vasculature relative to tubular structures in the central region of rat kidney inner medulla from the base through the first 3 mm by combining immunohistochemistry and semiautomated image acquisition techniques with graphical modeling software. Segments of descending vasa recta (DVR), ascending vasa recta (AVR), descending thin limb (DTL), ascending thin limb (ATL), and collecting duct (CD) were identified with antibodies against segment-specific proteins associated with solute and water transport (urea channel B, PV-1, aquaporin-1, ClC-K1, aquaporin-2, respectively) by immunofluorescence. Results indicate: 1) DVR, like DTLs, are excluded from CD clusters that we have previously shown to be the organizing element for the inner medulla; 2) AVR, like ATLs, are nearly uniformly distributed transversely across the entire inner medulla outside of and within CD clusters; 3) DVR and AVR outside CD clusters appear to be sufficiently juxtaposed to permit good countercurrent exchange; 4) within CD clusters, about four AVR closely abut each CD, surrounding it in a highly symmetrical fashion; and 5) AVR abutting each CD and ATLs within CD clusters form repeating nodal interstitial spaces bordered by a CD on one side, one or more ATLs on the opposite side, and one AVR on each of the other two sides. These relationships may be highly significant for both establishing and maintaining the inner medullary osmotic gradient.

Animals↗
PubMed1993

In vitro perfusion of chinchilla thin limb segments: urea and NaCl permeabilities.

We measured the urea and NaCl permeabilities (Purea and PNaCl, respectively) of the following nephron segments from chinchilla: the upper part of the long-loop descending limb (from outer medulla, LDLu), the middle part of the long-loop descending limb (from outer 30% of the inner medulla, LDLm), the lower part of the long-loop descending limb (from deep inner medulla, LDLl), and the thin ascending limb (from deep inner medulla, ATL). We found that Purea (x10(-5) cm/s) was relatively low in the LDLu (3.3), but that the value was larger in the inner medullary thin descending limb (16.8 for LDLm and 47.6 for LDLl). The ATL had an even higher value (170). Phloretin, 0.25 mM, added to the peritubular bath had no effect on Purea of these segments, suggesting that the rapid transport rate is not due to a phloretin-sensitive facilitated transport pathway like that seen in the inner medullary collecting duct. PNaCl (x10(-5) cm/s) also increased with distance along the length of the thin descending limb (LDLu, 11.7; LDLm, 41.2; LDLl, 98.4; and ATL, 321). Calculations from NaCl dilution potential measurements showed that LDLu was Na+ permselective, whereas LDLl and ATL were Cl- permselective. High solute permeabilities in the inner medullary thin descending limb contradict a major requirement of the passive model of urinary concentration developed previously (J. P. Kokko and F. C. Rector, Jr. Kidney Int. 2: 214-223, 1972; and J. L. Stephenson. Kidney Int. 2: 85-94, 1972).

Animals↗
PubMed1995

Amiloride-sensitive Na+/H+ antiporter in basolateral membrane of hamster ascending thin limb of Henle's loop.

The mechanisms of intracellular pH (pHi) regulation were investigated in the in vitro microperfused hamster ascending thin limb (ATL) of Henle's loop with the fluorescent pH indicator, 2',7'-bis(carboxyethyl)-5(6)-carboxyfluorescein. pHi of ATL cells was 7.05 +/- 0.02 (n = 30) when microperfused with a CO2/HCO(3-)-buffered solution. In HEPES-buffered solution, pHi was 7.10 +/- 0.02 (n = 16), which was significantly higher than the value in CO2/HCO(3-)-buffered solution (P < 0.05, n = 16). In HEPES-buffered solution, elimination of Na+ and addition of 1 mM amiloride to basolateral solution decreased the pHi by 0.12 +/- 0.03 (n = 6) and 0.11 +/- 0.02 (n = 5) at 1 min, respectively. The same manipulations in the luminal solution had no effect on pHi. One millimolar of N-ethylmaleimide (NEM) added to either side of ATL caused no significant change in pHi. Elimination of K+ on either side of ATL did not alter pHi. After adding 20 mM NH4Cl to basolateral solution, pHi instantaneously increased from 7.17 +/- 0.01 to 7.51 +/- 0.03 (n = 3), and then returned to steady-state level of 7.21 +/- 0.05 (n = 15) in 3 min. Removal of NH4Cl from basolateral solution then caused a rapid fall in pHi to 6.31 +/- 0.05 (n = 15), followed by spontaneous recovery at a rate of 0.43 +/- 0.06 unit/min (n = 15).(ABSTRACT TRUNCATED AT 250 WORDS)

Amiloride↗
PubMed1995

Convective uphill transport of NaCl from ascending thin limb of loop of Henle.

In this paper we describe a mathematical model of the renal inner medulla based on a previously proposed model [A.S. Wexler, R.E. Kalaba, and D.J. Marsh. Am. J. Physiol. 260 (Renal Fluid Electrolyte Physiol. 29): F368-F383, 1991] in which in the inner medullary ascending thin limb of Henle's loop (ATL) and collecting duct (CD) exchange with a local capillary node with the reabsorbed water and solutes flowing radially toward a central vascular bundle. Our model differs in that ascending and descending vasa recta and surrounding interstitial space are replaced by a central core. Our analysis of the coupled ATL-CD system shows that it is theoretically capable of transporting NaCl out of the ATL into the central vascular space (approximated by the central core) against a concentration gradient, which in the absence of radial diffusion can be arbitrarily large. By numerical solution of the model with the radial diffusion coefficient (D(r)) for NaCl of 0, we find that the ATL can be more than 100 mosmol/l hypotonic with respect to the core. We also find that with restricted diffusion the osmolality of the CD at the papilla is significantly greater than that of the loop of Henle. As D(r) approaches the diffusion coefficient of NaCl in free solution, the osmolality of the loop increases and that of the CD decreases. Thus, overall, contrary to intuitive expectations, the radial separation and uphill transport of NaCl do not give any significant increase in loop concentration, which depends primarily on the quantity of urea reabsorbed from the CD.

Animals↗
PubMed1995

Comparison of central core and radially separated models of renal inner medulla.

In this paper we describe the effect of partitioning exchange of ascending thin limb (ATL) and collecting duct (CD) between a central vascular space (CORE) and a radially separated capillary node (NODE) in a mathematical model of the concentrating mechanism of the renal inner medulla. A detailed description of the model has been provided [J. L. Stephenson, J. F. Jen, H. Wang, and R. P. Tewarson. Am. J. Physiol. 268 (Renal Fluid Electrolyte Physiol. 37): F680-F692, 1995]. We define a partition coefficient theta, which denotes the fractional exchange of CD and ATL with the NODE. Thus with theta = 0 we have a central core model, in which the ATL and CD exchange with the CORE only, and with theta = 1 we have a totally radially separated model, in which the ATL and CD exchange with the NODE only. Decreasing the partition coefficient from 1 to 0 effects a continuous transition from a totally radially separated model to a central core model. As this transition progresses with increasing exchange with the CORE, the osmolalities in all structures become nearly the same at the papilla, and the ability to transport salt uphill is lost. This is true even with no radial diffusion. However, radial diffusion and direct exchange with the CORE act synergistically in decreasing osmolality differences at the papilla and the capacity for convective uphill transport. These are lost in a more or less parallel way. There is, however, no significant concomitant change in concentrating ability. These results indicate that models with radial mixing of the interstitial vascular space are probably reasonably good approximations for the inner medulla.

Animals↗
PubMed2004

Loss of thioredoxin-binding protein-2/vitamin D3 up-regulated protein 1 in human T-cell leukemia virus type I-dependent T-cell transformation: implications for adult T-cell leukemia leukemogenesis.

Human T-cell leukemia virus type I (HTLV-I) is the causative agent of adult T-cell leukemia (ATL). However, the low incidence of ATL among HTLV-I-infected carriers, together with a long latent period, suggests that multiple host-viral events are involved in the progression of HTLV-I-dependent transformation and subsequent development of ATL. Human thioredoxin (TRX) is a redox active protein highly expressed in HTLV-I-transformed cell lines, whereas the TRX-binding protein-2/vitamin D3 up-regulated protein 1 (TBP-2/VDUP1) was recently identified as a negative regulator of TRX. We report here that expression of TBP-2 is lost in HTLV-I-positive, interleukin-2-independent T-cell lines but maintained in HTLV-I-positive, interleukin-2-dependent T-cell lines, as well as HTLV-I-negative T-cell lines. Ectopic overexpression of TBP-2 in HTLV-I-positive T cells resulted in growth suppression. In the TBP-2-overexpressing cells, a G1 arrest was observed in association with an increase of p16 expression and reduction of retinoblastoma phosphorylation. The results suggest that TBP-2 plays a crucial role in the growth regulation of T cells and that the loss of TBP-2 expression in HTLV-I-infected T cells is one of the key events involved in the multistep progression of ATL leukemogenesis.

Carrier Proteins↗
PubMed2004

Human T-cell lymphotropic virus type I-infected cells extravasate through the endothelial barrier by a local angiogenesis-like mechanism.

Extravasation of tumor cells through the endothelial barrier is a critical step in cancer metastasis. Human T-cell lymphotropic virus type I (HTLV-I)-associated adult T-cell leukemia/lymphoma (ATL) is an aggressive disease characterized by visceral invasion. We show that ATL and HTLV-I-associated myelopathy patients exhibit high plasma levels of functional vascular endothelial growth factor and basic fibroblast growth factor. The viral oncoprotein Tax transactivates the promoter of the gap-junction protein connexin-43 and enhances gap-junction-mediated heterocellular communication with endothelial cells. The interaction of HTLV-I-transformed cells with endothelial cells induces the gelatinase activity of matrix metalloproteinase (MMP)-2 and MMP-9 in endothelial cells and down-regulates the tissue inhibitor of MMP. This leads to subendothelial basement membrane degradation followed by endothelial cell retraction, allowing neoplastic lymphocyte extravasation. We propose a model that offers a mechanistic explanation for extravasation of HTLV-I-infected cells: after specific adhesion to endothelia of target organs, tumor cells induce a local and transient angiogenesis-like mechanism through paracrine stimulation and direct cell-cell communication with endothelial cells. This culminates in a breach of the endothelial barrier function, allowing cancer cell invasion. This local and transient angiogenesis-like sequence that may facilitate visceral invasion in ATL represents a potential target for ATL therapy.

CD4-Positive T-Lymphocytes↗
PubMed2004

Activating Fc receptors are required for antitumor efficacy of the antibodies directed toward CD25 in a murine model of adult t-cell leukemia.

We previously showed therapeutic efficacy of humanized anti-Tac (HAT), murine anti-Tac (MAT), and 7G7/B6 monoclonal antibodies, which recognize CD25, for human adult T-cell leukemia (ATL) in a murine model. In this study, we investigated the mechanism underlying the tumor-killing action mediated by these antibodies on an ATL model in nonobese diabetic/severe combined immunodeficient (SCID/NOD) wild-type mice that lack effective T and natural killer (NK) cells and in SCID/NOD Fc receptor common gamma chain knockout (FcRgamma-/-) mice. The ATL model was established by i.p. injection of human ATL cells (MET-1) into SCID/NOD wild-type or SCID/NOD FcRgamma-/- mice. HAT, MAT, and 7G7/B6 were given to the leukemia-bearing mice at a dose of 100 microg weekly for 4 weeks. The three antibodies inhibited the leukemia growth significantly in SCID/NOD wild-type mice, as monitored by serum levels of human beta2-microglobulin (P < 0.01), and prolonged survival of the leukemia-bearing SCID/NOD wild-type mice (P < 0.01) as compared with the control group. However, none of the antibodies manifested efficacy on the leukemia growth and survival of the SCID/NOD FcRgamma-/- mice bearing MET-1 leukemia. In a pharmacokinetics study, the blood concentrations of the radiolabeled antibodies decreased with time similarly in SCID/NOD wild-type and SCID/NOD FcRgamma-/- mice. Although NK cells may play a role in humans, in this murine model FcRgamma receptors on non-NK cells, such as polymorphonuclear leukocytes or monocytes, are required for the tumor-killing action of the antibodies directed toward CD25.

Animals↗
PubMed2006

NIK-333 inhibits growth of human T-cell leukemia virus type I-infected T-cell lines and adult T-cell leukemia cells in association with blockade of nuclear factor-kappaB signal pathway.

Adult T-cell leukemia (ATL) is caused by human T-cell leukemia virus type I (HTLV-I) and remains incurable. NIK-333, a novel synthetic retinoid, prevents the recurrence of human hepatoma after surgical resection of primary tumors. We explored the effects of NIK-333 on HTLV-I-infected T-cell lines and ATL cells. NIK-333 inhibited cell proliferation, induced G1 arrest, and resulted in massive apoptosis in all tested HTLV-I-infected T-cell lines and ATL cells, whereas little effect was observed on normal peripheral blood mononuclear cells. NIK-333 treatment decreases the levels of cyclin D1, cyclin D2, cIAP2, and XIAP proteins. Further analysis showed that NIK-333 inactivated nuclear factor-kappaB in HTLV-I-infected T-cell lines. In animal studies, treatment with NIK-333 (100 mg/kg given orally every other day) produced partial inhibition of growth of tumors of a HTLV-I-infected T-cell line transplanted s.c. in severe combined immunodeficient mice. Our results indicate that NIK-333 is a potentially useful therapeutic agent for patients with ATL.

Animals↗
PubMed1999

A 13-year experience with epilepsy surgery.

Between 1985 and 1997, 563 therapeutic craniotomies were performed: 311 anterior temporal (ATL) and 158 extramesial temporal (XMT) resections, 67 callosotomies, 20 hemispherectomies and 7 multiple subpial transections. Sixty-seven percent of nonlesional ATL cases were seizure free (SF), and 76% of nonlesional ATL cases < or =18 years old were SF. Seventy-eight percent of lesional ATL cases with complete resection were SF. Seventy-three percent of lesional cases < or =18 were SF. Thirty-seven percent of nonlesional XMT cases were SF. Seventy percent of XMT lesional cases with complete resection were SF, and 82% of lesional XMT cases < or =18 were SF. Of the anterior callosotomy cases, there was a > or =90% decrease in generalized tonic-clonic seizures in 50% of patients, and in tonic seizures, drop attacks, absence and myoclonic seizures in approximately 60-70% of patients. Of 20 hemispherectomies, 65% were SF. Of 7 multiple subpial transections, 29% were SF.

Adult↗
PubMed1998

Distributional patterns of phospholipase C isozymes in rat kidney.

As the first step to investigate the physiological function of phospholipase C (PLC), we determined the distribution patterns of PLC isozymes in normal rat kidneys using Western blotting analysis and immunohistochemistry. Western blotting analysis was performed in four regions (cortex, outer stripe and inner stripe of the outer medulla, and the inner medulla). PLC-beta1 and beta3 were detected in the inner stripe of the outer medulla and the inner medulla. PLC-gamma1 was distributed homogeneously along the corticomedullary axis. PLC-gamma2 was observed in the medulla and PLC-delta1 showed a gradual increase from the cortex to the inner medulla. In contrast, no PLC-beta4 was detected in all regions. On immunohistochemistry, the immunoreactivities to PLC antibodies were observed as follows: PLC-beta1, from the thick ascending limb (TAL) to the inner medullary collecting tubule (IMCT); PLC-beta3, in the glomerulus (Glm), the ascending thin limb (ATL) and the collecting tubule; PLC-beta4, Glm, the proximal convoluted tubule (PCT), ATL, the distal convoluted tubule, the connecting tubule, and the collecting tubules; PLC-gamma1, PCT, TAL and IMCT; PLC-delta1, homogeneously from PCT to IMCT. PLC-beta3 immunoreactivities were detected in the nuclei of the TAL, ATL, outer medullary collecting tubule (OMCT) and IMCT. PLC-beta4 and gamma2 were observed in Glm, MTAL, ATL, OMCT and IMCT. These results suggest the intrarenal site-specific existence of PLC isozymes that may regulate kidney functions through the PLC-mediated signal transductions.

Animals↗
PubMed1995

Epidemiological features of HTLV-I and adult T cell leukemia.

Adult T-cell leukemia (ATL) patients and human T-cell leukemia virus type I (HTLV-I) carriers are clustered in limited groups in the world, especially among Japanese in Asia, Blacks in Central Africa, Melanesians in Papua New Guinea and Andeans in South America. The major transmission routes of HTLV-I under natural conditions are from mother-to-child through breast milk and from man-to-woman through semen. The whole life risk of ATL among persistent HTLV-I carriers is estimated at 2-6%. The detailed manifestation mechanism of ATL is not yet clarified; however, it is certain that HTLV-I infection in infancy is the main cause of ATL. Therefore, the prevention measure against mother-to-child transmission of HTLV-I is indispensable from a viewpoint of public health.

Adult↗
PubMed1989

Adult T cell leukemia in hemodialysis patients from the Kagoshima district, an area in which human T cell leukemia virus type I is highly endemic.

We report 2 cases of adult T cell leukemia (ATL) from hemodialysis (HD) patients with chronic renal failure (CRF) in the Kagoshima district, an endemic area of human T cell leukemia virus type I(HTLV-I) in Japan. The positivity of antibodies to ATL-associated antigen(anti-ATLA) in HD patients, regardless of whether or not blood transfusions were given, has been higher than in healthy persons in the district (p less than 0.01). ATL is considered to break out from HTLV-I carriers. Further study should be conducted to clarify the relationship between HTLV-I infection and CRF, and moreover, attention should be directed not only to treatment of HD but accompanying ATL as well, particularly in HTLV-I-endemic areas.

Aged↗