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Biomedical subjects

W W Hall

Publications and source records attributed to W W Hall.

At least 55 records · Page 3Linked to original sources

Anti-viral and immunomodulatory effects of interferon-alpha on cultured lymphocytes from patients with human T lymphotropic virus type I-associated myelopathy (HAM/TSP).

In contrast to therapeutic benefits of interferon-alpha (IFN-alpha) in patients with human T lymphotropic virus type I (HTLV-I)-associated myelopathy/tropical spastic paraparesis (HAM/TSP), little is known about the mechanisms underlying its clinical efficacy. To investigate the anti-viral and/or immunomodulatory properties of IFN-alpha in HTLV-I infection, the effects of IFN-alpha on HTLV-I-induced in vitro phenomena were evaluated. In vitro activation of HTLV-I in fractionated CD4+ T lymphocyte-rich cells (CD4+ cells) could be demonstrated by increased thymidine incorporation into the cells, detection of proviral HTLV-I and viral RNA, and by assays of reverse transcriptase activities in culture supernatants. T cell immune responses were evaluated by thymidine incorporation into CD8+ T lymphocyte-rich cells (CD8+ cells) responding to cultured and irradiated autologous CD4+ cells possessing HTLV-I antigens. It could be shown that IFN-alpha suppressed both the in vitro activation of HTLV-I and the CD8+ cell response. Moreover, 1 day supplementation of IFN-alpha as a pretreatment was sufficient for the induction of these properties. These findings, together with the clinical efficacy of IFN-alpha administration in patients with HAM/TSP, support the view that viral activation and T cell responses are critical components in the pathogenic processes involved in HAM/TSP.

Antiviral Agents↗

Nucleotide sequence and restriction fragment length polymorphism analysis of the long terminal repeat of human T cell leukemia virus type II.

Molecular studies have demonstrated the existence of two major subtypes of human T cell leukemia virus type II: HTLV-IIa and HTLV-IIb. In attempts to further classify this family of viruses we have carried out nucleotide sequence and restriction fragment length polymorphism (RFLP) analysis of the long terminal repeat (LTR), a region that has been shown in previous studies to have the greatest intra- and intersubtype genomic divergence. Analysis of the nucleotide sequences suggested the existence of distinct phylogenetic groups in each subtype and, on the basis of predicted differences in restriction endonuclease sites, RFLP analysis allowed the identification of four groups within the IIa subtype (a1-a4) and six within the IIb subtype (b1-b6). Nucleotide sequence analysis also suggested the possible existence of HTLV-II quasispecies. However, this appeared not to be significant, and preliminary studies suggest that these would not be expected to influence the results of RFLP analysis appreciably. The validity of the RFLP method was demonstrated in an analysis of 36 randomly chosen samples from HTLV-II seropositive blood donors from the New York City Blood Center, where it could be shown that all could be successfully classified. Moreover, the RFLP analysis correctly matched the viruses in donors and recipients of contaminated blood in four situations in which HTLV-II was inadvertently transmitted by transfusion. RFLP analysis of the LTR appears to be a rapid and reliable method by which to identify HTLV-II infection. This should prove useful in studies of the epidemiology and the characterization of viruses present both in nonindigenous and indigenous populations.

Base Sequence↗

Extraordinary high rate of HTLV type II seropositivity in intravenous drug abusers in south Vietnam.

Serum specimens (n = 1899) were assayed for infections with HTLV-I, HTLV-II, and HIV-1 in seven classified groups of normal healthy controls, children, pregnant women, prostitutes, intravenous drug abusers, patients under going hemodialysis, and hemophiliacs in South and North Vietnam. Surprisingly, 125 of 954 samples from South Vietnam exhibited seropositivity for HTLV-II and 119 of these belonged to the group of IVDAs (n = 200). The remaining six positives were a healthy control, a prostitute, two children, and two patients under going hemodialysis. Two IVDAs who were seropositive for HTLV-I and 10 of 15 seropositives for HIV-1 were also positive for HTLV-II in this population. In contrast, no seropositives to any of the viruses were detected in the North Vietnamese samples (0 of 945). The HTLV-II-seropositive IVDAs exhibited increased seropositivity with age compared with HIV-1 seropositivity in the population, and there was no statistical relation between seropositivity for HTLV-II and HIV-1. The HTLV-IIs in South Vietnam IVDAs appeared, by subtype-specific peptide ELISA, to be a mixture of both subtypes a and b, with subtype a predominant. It seems possible that HTLV-II may have been introduced into this population from IVDAs from the United States during the Vietnam conflict, but in a period prior to, or early in, the introduction of HIV-1 to IVDAs.

Adult↗

Continued prescribing of inappropriate drugs in general practice.

Seven general practitioners used various methods to identify patients in their practices whom they had inherited and whose medication they regarded as inappropriate in the light of current knowledge. Information was collected in each case about the drug concerned, the patient, the original prescriber, and the reason for continued prescribing. Each patient was also interviewed. Altogether, 25 different drugs were prescribed for 40 patients: in 16 the inappropriate drug was one acting on the brain, in 13 an antihypertensive, in seven it was given for heart disease and in three, for asthma. The influence of the original prescriber, and the patient's dependence on the drug, helped to explain its continued use. Almost half the patients said that they might consider changing their medication. The study underlines the importance of reviewing long-term medication and offers a method of scrutinizing repeat prescribing in general practice. Community pharmacists could help in this process.

Adult↗

Occurrence of multiple JC virus variants with distinctive regulatory sequences in the brain of a single patient with progressive multifocal leukoencephalopathy.

We established 99 JC virus (JCV) DNA clones directly from the brain of a single patient with progressive multifocal leukoencephalopathy (PML). Based upon restriction patterns, the cloned viral DNAs were classified into two major groups (NY-1A and -1B) containing 53 and 35 clones, respectively, and several minor groups containing one or a few clones. The regulatory sequences of representative clones were compared with the archetypal regulatory sequence, which has been detected in JCV DNAs cloned from the urine of healthy and nonimmunosuppressed individuals. The regulatory sequence of NY-1B had the two structural features common to most PML-type regulatory regions, duplication and deletion of specific segments in the archetypal sequence, while that of NY-1A contained a small deletion and an insertion of a 29-bp sequence originating from the early region of the JCV genome. A regulatory region similar to that of NY-1A has never been detected in JCV isolates obtained thus far.

AIDS-Related Opportunistic Infections↗

Transmission of human T cell lymphotropic virus (HTLV) type II by transfusion of HTLV-I-screened blood products.

Blood donors have been screened for antibodies to human T cell lymphotropic virus (HTLV) type I since December 1988. Screening for HTLV-II has been simultaneously done because of cross-reactivity between antibodies to the two viruses. Currently, < 1 in 10,000 US blood donors is positive for HTLV-I or -II. Lookback studies led to the identification of 6 HTLV-II-infected patients. Three received transfusions before introduction of HTLV-I screening tests, while the other 3 received blood components that tested negative for HTLV-I. The HTLV-II subtypes of each of 4 donor/recipient pairs, as determined by DNA amplification using polymerase chain reaction, were identical, supporting the view that transfusions were the source of infection. In conclusion, currently licensed blood donor screening tests for HTLV-I lack sensitivity for HTLV-II, and transfusion of blood from HTLV-II-infected donors that test negative on HTLV-I screening tests may result in infection.

Adult↗

Acquired ichthyosis in concomitant HIV-1 and HTLV-II infection: a new association with intravenous drug abuse.

BACKGROUND: Papulosquamous eruptions are common in HIV-1-infected patients. Acquired ichthyosis may occur after profound T-cell depletion. Intravenous drug users infected with HIV-1 can be coinfected with human lymphotropic virus II (HTLV-II). OBJECTIVE: We examined the relation between acquired ichthyosis and concomitant infection with HIV-1 and HTLV-II in intravenous drug users. METHODS: We examined 184 male and female HIV-1-positive intravenous drug users for acquired ichthyosis. Enzyme-linked immunosorbent assay was used to screen these patients for antibody to HTLV-I/II. Western blot, viral isolation, and the polymerase chain reaction were used to confirm that serologic responses were from HTLV-II and not HTLV-I. RESULTS: Acquired ichthyosis occurred in 6.3% of white, 16.4% of Hispanic, and 21.7% of black patients. It occurred only after profound helper T-cell depletion, in association with increasing age, and with concomitant infection with HTLV-II (22.2% vs. 6.8% in HIV-1 singly infected patients [p < 0.038]). CONCLUSION: Acquired ichthyosis may be a marker of concomitant infection with HIV-1 and HTLV-II in intravenous drug users and occurs after profound helper T-cell depletion.

Acquired Immunodeficiency Syndrome↗

Nucleotide sequence analysis of human T cell leukemia virus, type II (HTLV-II) isolates.

A study by Hall et al. (J Virol 1992;66:2456-2463; Ref. 11) has suggested the existence of two closely related molecular subtypes of HTLV-II, which were tentatively designated HTLV-IIa and HTLV-IIb. To confirm this nucleotide sequence analysis of 986 bp of the env gene region encoding the entire surface glycoprotein, gp46, and the amino terminus of the transmembrane glycoprotein, gp21, of 10 HTLV-II isolates was carried out. The results clearly established the existence of two subtypes and demonstrated a 4.3% divergence in sequence in this region. Analysis of other gene regions of the provirus, including the pol (1544 bp), gag (448 bp), and the entire LTR (743 bp) of two representative isolates of each subtype, showed a sequence divergence of 3.8 to 5.7%, with greatest divergence occurring in the LTR. In addition to single nucleotide changes, the gag regions encoding the structural protein, p19, of the HTLV-IIb isolates were also found to have a 66-bp deletion that would be expected to result in a p19 protein having a 22-amino acid deletion in the carboxy-terminus region. Attempts to exploit this to differentiate the two subtypes serologically were unsuccessful in that recombinant p19 proteins of both subtypes were found to be antigenically cross-reactive. The finding of two molecular subtypes of HTLV-II may have important implications for a better understanding of the biological and pathogenic properties of the virus, and will be useful in characterizing the viruses present in endemic foci in American Indian populations.

Amino Acid Sequence↗

Endemic human T cell leukemia virus type II infection in southwestern US Indians involves two prototype variants of virus.

Human T cell leukemia virus (HTLV) type II is endemic in certain American Indians, and high rates of infection occur in intravenous drug users (IVDUs). North American IVDUs are infected with two distinct variants, HTLV-IIa and -IIb. If IVDUs became infected as a result of interaction with members of an American Indian population, both viral forms should be demonstrable in such populations. Nucleotide sequence analysis of 630 bases of the env gene encoding the gp21 protein was done on DNA from 12 New Mexico Indians (8 Pueblo, 4 Navajo). All samples were typical subtype a or b viruses. Seven of the 8 Pueblo and 2 of 4 Navajo had subtype b; the rest had subtype a. The results are compatible with an indigenous New World origin for both subtypes of HTLV-II.

Adult↗

Aggressive natural killer cell lymphoma/leukemia. A recently recognized clinicopathologic entity.

We report a comprehensive study of a case of aggressive natural killer cell lymphoma/leukemia, which is characterized by young male predominance, rapidly progressive clinical course, and presence of lymphadenopathy, hepatosplenomegaly, and bone marrow involvement. The leukemic phase is frequently preceded by pancytopenia. The diagnostic clues are the detection of cytoplasmic granules in tumor cells on Wright-Giemsa-stained tissue imprints or smears and a selective loss of T-cell antigens. Immunophenotyping is decisive in making the final diagnosis by showing positive natural killer cell markers (CD16, CD56, and/or CD57), CD2, CD11c, and Ia, but negative CD3, T-cell receptor heterodimers, terminal deoxynucleotidyl transferase, and B-cell markers. Genotyping always shows germline configuration in both immunoglobulin and T-cell receptor genes. The unique feature in this case is its presentation as a testicular lymphoma, which has not been previously reported. Polymerase chain reaction was performed in this case but failed to detect human T-cell leukemia virus type I/II provirus. It is important to recognize this new entity as it is a highly aggressive disease with a rapidly progressive clinical course and fails to respond to any chemotherapeutic regimen available.

Adult↗

Identification of human T cell leukemia virus type IIb infection in the Wayu, an aboriginal population of Colombia.

Human T cell leukemia virus type II (HTLV-II) is endemic in a number of native American populations and high rates of infection have also been demonstrated in intravenous drug abusers (IVDAs). Studies of virus isolates in the latter population have shown the existence of two closely related subtypes of the virus, HTLV-IIa and HTLV-IIb. To characterize the viruses present in native Americans, we analyzed by nucleotide sequence analysis the proviruses from the Wayu, an aboriginal population residing in Colombia, South America. The results showed HTLV-IIb infection in this population, and also demonstrated remarkable conservation of sequence when compared to the proviruses in IVDAs.

Base Sequence↗

In vivo cellular tropism of human T cell leukemia virus type II (HTLV-II).

To investigate the in vivo cellular tropism of human T cell leukemia virus type II (HTLV-II), subpopulations of fresh peripheral blood mononuclear cells from infected individuals were isolated and analyzed by polymerase chain reaction for the presence of provirus. In eight of nine patients, HTLV-II was detected exclusively in the CD8+ T lymphocyte population. In the remaining patient, provirus was also detected in CD4+ T lymphocytes. Provirus was not detected in B lymphocytes or monocytes of any patient. These results suggest that in vivo HTLV-II has a preferential, and perhaps in some cases, an exclusive tropism for CD8+ T lymphocytes. The findings contrast sharply with those on HTLV-I where there is a preferential tropism for CD4+ T lymphocytes. Although HTLV-II infection has not been consistently associated with any lymphoproliferative disorders, the results suggest that if these occur, they may be different from those known to be associated with HTLV-I.

Adult↗

Multiple isolates and characteristics of human T-cell leukemia virus type II.

Human T-cell leukemia (or lymphotropic) virus type II (HTLV-II) was isolated from eight HTLV-seropositive patients, six of whom were also infected with human immunodeficiency virus, by cocultivation of peripheral blood mononuclear cells (PBMCs) with BJAB, a continuous B-cell line. Restriction endonuclease mapping of the proviruses demonstrated consistent differences among isolates, and two distinct physical map patterns were observed. The results suggest the existence of two closely related molecular subtypes of HTLV-II, which are tentatively designated HTLV-IIa and HTLV-IIb. This finding was supported by preliminary nucleotide sequence analysis of the env gene region encoding the transmembrane glycoprotein gp21, which showed consistent differences between the two proposed virus subtypes. Exploitation of differences in restriction endonuclease sites allowed polymerase chain reaction amplification to detect and differentiate the two subtypes in fresh PBMCs of HTLV-seropositive intravenous drug abusers (IVDAs). The results of these studies confirm that HTLV-II infection is the prominent HTLV infection in seropositive IVDAs and also show that infection with both subtypes occurs. The finding of genetic heterogeneity in the HTLV-II group of viruses may have important implications for studies on its role in human disease and will be useful in characterizing the viruses present in newly discovered endemic foci in New World indigenous populations.

Adult↗

Deleted HTLV-I provirus in blood and cutaneous lesions of patients with mycosis fungoides.

Mycosis fungoides, a rare form of cutaneous T cell leukemia/lymphoma, is suspected of having a viral etiology on the basis of certain similarities to adult T cell leukemia, which is associated with human T cell leukemia/lymphoma virus type I (HTLV-I) infection. Cell lines were established from peripheral blood mononuclear cells (PBMC) of an HTLV-I-seronegative patient with mycosis fungoides. DNA hybridization analysis revealed the presence of HTLV-I-related sequences with unusual restriction endonuclease sites. Sequence analysis of subcloned fragments demonstrated the presence of a monoclonally integrated provirus with a 5.5-kilobase deletion involving large regions of gag and env and all of pol. Additional evidence for the presence of deleted proviruses was found by polymerase chain reaction (PCR) amplification of DNA from cutaneous lesions of five other HTLV-I-seronegative patients. The findings suggest that HTLV-I infection may be involved in the etiology of at least certain cases of mycosis fungoides.

Base Sequence↗

Identification of type-specific linear epitopes in the glycoproteins gp46 and gp21 of human T-cell leukemia viruses type I and type II using synthetic peptides.

Synthetic peptides of 20-25 amino acids were employed in enzyme-linked immunosorbent assays to identify linear epitopes in the external glycoprotein gp46 and the transmembrane glycoprotein gp21 of human T-cell leukemia/lymphotropic viruses type I (HTLV-I) and II (HTLV-II). Ten linear epitopes were identified in the HTLV-I glycoproteins, seven in gp46 and three in gp21. Three major linear epitopes were identified in the gp46 of HTLV-II. Peptides representing linear epitopes of gp46 were found to be sensitive and specific for the detection of antibody and permit serological identification and differentiation of HTLV-I and HTLV-II infections.

Amino Acid Sequence↗