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W W Hall

Publications and source records attributed to W W Hall.

At least 37 records · Page 2Linked to original sources
PubMed1998

Clonal expansion within CD4+ and CD8+ T cell subsets in human T lymphotropic virus type I-infected individuals.

To investigate the diversity of the T cell repertoire involved in human T lymphotropic virus type I (HTLV-I) infections, peripheral blood T cell subsets were analyzed by using a PCR-based assay that permits determination of complementarity-determining region 3 (CDR3) length variation in TCR Vbeta transcripts. In two of four asymptomatic HTLV-I carriers and in four of five patients with HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP), mono- or oligoclonal expansions were detected in the CD4+ T cell subset. In one patient with adult T cell leukemia, a specific clone bearing Vbeta7 was detected in the CD4+ T cell subset. In contrast, clonal expansion was not observed in the CD4 T cell subsets of three individuals with asymptomatic HTLV-II infection or in our previous studies of a large number of uninfected individuals. Oligoclonal expansions in the CD8+ T cell subset were detected in all subjects, including the patient with adult T cell leukemia. No differences in the number of expanded clones were noted between asymptomatic carriers and in patients with HAM/TSP and there was no obvious restriction in the TCR V region usage. Direct sequencing revealed no significant bias in the CDR3 motifs utilized by the predominant clones. This report is the first direct demonstration of clonal expansions within fractionated T cell subsets (CD4+ and CD8+) in HTLV-I infections and suggests that 1) clonal expansion of CD4+ T lymphocytes likely occurs as a direct result of infection and 2) polyclonal CD8+ T cell expansion occurs frequently and independently of disease association.

Adult↗
PubMed1998

Identification and molecular characterization of human T lymphotropic virus type II infections in intravenous drug abusers in the former South Vietnam.

Previous serological studies have demonstrated that some 60% of intravenous drug abusers (IVDAs) in urban areas of the former South Vietnam are infected with HTLV-II. In the present report we have attempted to characterize the viruses using restriction fragment length polymorphism (RFLP) and nucleotide sequence analysis of the provirus long terminal repeat (LTR) region. RFLP analysis of nine samples demonstrated that all were infected with the HTLV-IIb subtype. The HTLV-IIa subtype was not detected. Phylogenetic analysis of the nucleotide sequences demonstrated that the viruses clustered closely with HTLV-IIb isolates present in IVDAs from the New York City area. The present molecular analysis together with the previously reported absence of HTLV-II infection in North Vietnam supports the view that HTLV-II may have been introduced from the United States to this part of Asia by military personnel during the Vietnam conflict.

HTLV-II Infections↗
PubMed1998

Reflux of HTLV-I infected lymphocytes from the privileged compartment(s) to peripheral blood flow in patients with HTLV-I-associated myelopathy.

To understand the mechanisms involved in the pathogenesis of human T lymphotropic virus type I (HTLV-I)-associated myelopathy/tropical spastic paraparesis (HAM/TSP), three in vivo phenomena which have been observed in the peripheral blood of patients and differing from that in asymptomatic HTLV-I carriers must be taken into consideration: (a) the presence of increased HTLV-I viral load, (b) a higher immune responsiveness against HTLV-I antigens, and (c) biased nucleotide substitutions in the HTLV-I pX region which indicate a decreased selection pressure for viral amino acid changes. We now propose a hypothesis which focuses on the in vivo dynamics of HTLV-I infected lymphocyte migration and which incorporates these features. In addition, the hypothesis assumes the existence of a deviation in immune surveillance for HTLV-I in the central nervous system (CNS) in spite of the presence of frequent specific immune effectors. We suggest that in the active phase of HAM/TSP, accompanied with or following autoaggressive interactions between infected lymphocytes and immunocompetent cells in the CNS, there is a consequential reflux of the infected lymphocytes to the peripheral blood. The reflux of infected cells would be expected to provide peripheral blood with tissue-derived HTLV-I proviruses which have been indulged and propagated in an immune-privileged site. This process would result in and account for the observed increase in viral load and the substitution bias in HTLV-I sequences in the peripheral blood.

Deltaretrovirus Antibodies↗
PubMed1998

Negative-pressure dressings as a bolster for skin grafts.

Contoured wounds needing closure with skin grafts are often located in complex anatomic regions or are in unusual positions, which make conventional skin graft stabilization techniques cumbersome and ineffective. Often after 72 hours, a skin graft covered with a bolstered dressing has poor take secondary to shear stresses, as well as hematoma formation or serum collection, negating the effectiveness of the stabilizing dressing. The Food and Drug Administration has recently approved vacuum-assisted closure (V.A.C.), an innovative technique using negative pressure, for closure of chronic wounds. This reportedly leads to enhanced granulation tissue formation and consequently more rapid reepithelialization of wounds compared with conventional packing with saline-moistened gauze. Experimental studies have demonstrated increased oxygen tension, decreased bacterial counts, and increased granulation formation occurring under negative-pressure systems. Extending the use of this concept, we have coupled skin grafting with negative-pressure dressings for closure of large, complex open wounds. Our results indicate greater than 95% graft take in all patients in this study. This technique is extremely efficacious, with increased graft take due to total immobilization of the graft, thereby limiting shear forces, elimination of fluid collections, bridging of the graft, and decreased bacterial contamination. Moreover we have noted decreased edema in rotated muscle flaps, improved contour conformity, and shortened hospitalizations.

Aged↗
PubMed1997

A strategy for rapid, high-confidence protein identification.

A procedure is described for rapid, high-confidence identification of proteins using matrix-assisted laser desorption/ionization tandem ion trap mass spectrometry in conjunction with a genome database searching strategy. The procedure involves excision of copper-stained bands or spots from electrophoretic gels, in-gel trypsin digestion of the proteins, single-stage mass spectrometric analysis of the resultant mixture of tryptic peptides, followed by tandem ion trap mass spectrometric analysis of selected individual peptides, and database searching of the relevant genomic database using the program PepFrag. The scheme provides sensitive, real-time protein identification as well as facile identification of modifications. A single operator can unambiguously identify 5-10 proteins/day from an organism whose genome is known at a level of > 0.5 pmol of protein loaded on a gel. The utility of the technique was demonstrated by the identification and characterization of a band from a human HTLV-I preparation and 11 different proteins from a yeast RNA polymerase II C-terminal repeat domain-affinity preparation. The technology has great potential for postgenome biological science, where it promises to facilitate the dissection and anatomy of macromolecular assemblages, the definition of disease state markers, and the investigation of protein targets in biological processes such as the cell cycle and signal transduction.

Amino Acid Sequence↗
PubMed1997

Lack of evidence for the transmission of JC polyomavirus between human populations.

Human polyomavirus JC virus (JCV), the causative agent of progressive multifocal leukoencephalopathy, is ubiquitous in humans, infecting children asymptomatically then persisting in renal tissue. Since JCV DNA can readily be detected from urine, it should be a useful tool with which to study the mode of virus transmission in humans. Based on this notion, we examined the extent to which JCV was transmitted from the American to Japanese populations in Okinawa Island, Japan. (A population of about 50 000 American soldiers and families have been stationed in Okinawa since 1945.) Four JCV types (A to D) were identified in American populations in U.S.A., whereas only type B was prevalent in elder Japanese in Okinawa who had reached adulthood by 1945. Thus, types A, C, and D served as indicators of the transmission of JCV from American to Japanese populations. We then examined whether types A, C, and D were detectable in Japanese in Okinawa aged 30-50 years who may have been in contact with Americans during childhood. However, all the 125 isolates from the younger Japanese population were type B without exception. From this finding, we concluded that JCV is rarely transmitted between human populations.

Adult↗
PubMed1997

In vitro virus propagation and high cellular responsiveness to the infected cells in patients with HTLV-I-associated myelopathy (HAM/TSP).

The reasons for the development of HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP) in certain infected individuals remain poorly understood, but the susceptibility should involve both viral factors and host conditions. To assess simultaneously both virus-induced activation of infected cells and the cellular response to virus producing cells, an analysis of fractionated peripheral blood lymphocytes obtained from patients with HAM/TSP (n = 15) were compared with those of asymptomatic HTLV-I carriers (n = 9) in an age-matched manner. The in vitro propagation of HTLV-I infection was evaluated as the spontaneous thymidine incorporation into CD4+ cells, and proliferative response of CD8+ cells against cultured and irradiated autologous CD4+ cells was employed to analyze the HTLV-I-induced cellular response. The comparative analysis using these two parameters demonstrated that HAM/TSP patients were characterized by the concomitance of a high inducibility of HTLV-I propagation and a high cellular responsiveness against HTLV-I as compared with asymptomatic HTLV-I carriers, suggesting the involvement of both of these factors in disease susceptibility. In addition, the coupled evaluation of these two in vitro phenomena may offer a better diagnostic hallmark for HTLV-I seropositive myelopathy cases with other known cause of myelopathy.

Adult↗
PubMed1997

Managing epilepsy in general practice: the dissemination and uptake of a free audit package, and collated results from 12 practices in England and Wales.

This study aimed to assess the uptake and use by general practitioners of a free epilepsy audit protocol, and describe the care provided by practices which returned completed audits. A protocol for epilepsy audit in general practice was designed and described in the medical press. Practices were invited to reply. Responders were provided with the protocol. A total of 215 practices responded to the articles in the press. Questionnaires asking how they had used the audit protocol were sent to them 18 months later. One hundred and seventy (79%) of the 215 responding practices returned the questionnaires. Forty-seven (28%) had collected some or all of the data. Twenty-two (13%) submitted data of which 12 (7%) matched the original protocol. Aggregated list sizes for these 12 practices was 75689 and 502 (0.66%) patients were being treated. Of these, 60% were seizure free and 11% were having more than one seizure per month. Seventy-one were receiving monotherapy and only two patients were taking more than three drugs. Eighty-eight per cent of patients still having seizures had been seen by their GP for their epilepsy in the last 12 months. In 18% of cases, information on epilepsy lifestyle issues had been given and noted. Offering a free epilepsy audit package can stimulate interest amongst practices in the topic and resulted in 13% collecting and submitting their data for analysis. Practices reported a higher prevalence for epilepsy (0.66%) than in previous studies. The majority of patients with active epilepsy (88%) had been seen by a general practitioner in the last 12 months. Most (71%) were receiving monotherapy, but recording of seizure frequency and provision of information about epilepsy was low.

Anticonvulsants↗
PubMed1997

A rat model of Parkinson's disease induced by Japanese encephalitis virus.

In Fischer rats infected with Japanese encephalitis virus (JEV) at 13 days after birth and sacrificed 12 weeks later, the major pathological changes resembled those found in Parkinson's disease. Specifically there was neuronal loss with gliosis which was confined mainly to the zona compacta of the substantia nigra, with a notable absence of lesions in the cerebral cortex and cerebellum. Changes were bilateral being most severe in the central part of the zona compacta. Immunohistochemical studies with anti-tyrosine hydroxylase (TH) demonstrated that the number of TH-positive neurons was significantly decreased in the substantia nigra compared to controls, while comparable numbers of TH-positive neurons were found in the basal ganglia in both JEV-treated rats and age-matched controls. JEV-infected rats showed marked bradykinesia, with significant behavioral improvement being observed following administration of L-DOPA. Immunohistochemical studies failed to detect JEV antigens in any region of the rat brain and the JEV genome was undetectable in the substantia nigra and the cerebral cortex using the reverse transcription-polymerase chain reaction (RT-PCR). The findings suggest that JEV infection of rats under the conditions described may serve as a model of virus induced Parkinson's Disease.

Animals↗
PubMed1997

The role of topoisomerase I in HIV-1 replication.

The mechanisms involved in the restriction of the cellular tropism of HIV-1 to cells of primate origin remain to be clearly defined. However, a number of studies have shown that this is determined not only at the level of the cellular receptor(s) or virus entry, but at a number of additional and later stages in virus replication. We have recently reported that the reverse transcription of HIV-1 RNA is markedly enhanced by the association of the gag encoded nucleocapsid p15 protein and cellular topoisomerase 1. In the present study we have now investigated if the recruitment of cellular topoisomerase I during virus replication is important in determining the cellular tropism of HIV-1. Employing a stable murine cell line, L929, expressing both human CD4 and topoisomerase I, it could be demonstrated that effective proviral DNA synthesis occurred following infection. In contrast in cells expressing only human CD4 proviral DNA synthesis was not detected. In addition we have co-expressed fusin, a protein known to act as an accessory factor as the virus entry stage in infection of T cell tropic HIV-1, to support viral entry completely. However no progeny virus could be detected after HIV-1 infection. These results suggest that reverse transcription in vivo is critically dependent on the presence of cellular topoisomerase I, and support the view that involvement of this enzyme is in HIV-1 replication. Moreover the findings suggest that other factors which remained to be identified, are involved in restricting HIV-1 replication in non-primate cells.

Animals↗
PubMed1997

The role of topoisomerase I in HIV-1 replication.

The mechanisms involved in the restriction of the cellular tropism of HIV-1 to cells of primate origin remain to be clearly defined. However, a number of studies have shown that this is determined not only at the level of the cellular receptor(s) or virus entry, but at a number of additional and later stages in virus replication. We have recently reported that the reverse transcription of HIV-1 RNA is markedly enhanced by the association of the gag encoded nucleocapsid p15 protein and cellular topoisomerase I. In the present study we have investigated if the recruitment of cellular topoisomerase I during virus replication is important in determining the cellular tropism of HIV-1. Employing a stable murine cell line, L929, expressing both human CD4 and topoisomerase I, it could be demonstrated that effective proviral DNA synthesis occurred following infection. In contrast in cells expressing only human CD4, proviral DNA synthesis was not detected. In addition we have co-expressed fusin, a protein known to act as an accessory factor as the virus entry stage in infection of T cell tropic HIV-1, to support viral entry completely. However no progeny virus could be detected after HIV-1 infection. These results suggest that reverse transcription in vivo is critically dependent on the presence of cellular topoisomerase I, and support the view that involvement of this enzyme is important in HIV-1 replication. Moreover the findings suggest that other factors which remained to be identified, are involved in restricting HIV-1 replication in non-primate cells.

Animals↗
PubMed1996

A kinetic comparative study on lymphocyte responses to superantigen and phytohemagglutinin: reciprocal presentation of superantigen on the surface of activated lymphocytes.

The kinetics of thymidine incorporation into fractionated T lymphocytes responding to bacterial superantigens were compared to those of cells activated by phytohemagglutinin (PHA). Evident differences between the kinetics of cell proliferation induced by PHA-P and staphylococcal enterotoxin B (SEB) emerged after Day 4 of culture. PHA-P-induced proliferative responses of peripheral blood mononuclear cells (PBMCs) and fractionated cells were apparent on Day 4 because of the presence of accessory cells in the initial cell suspensions. This gradually diminished in correlation with the decline of accessory cells in the cultures. The SEB-induced cell growth (PBMCs and CD4+ cells), however, continued until Day 9 of the culture. This finding suggests the reciprocal usage of MHC class II molecules to present SEB by activated T lymphocytes for superantigen-induced T cell activation and suggests that superantigen-related immune activation may depend in part on the potential of activated T lymphocytes to mediate reciprocal cell-to-cell interactions in the presence of superantigens. The decline observed in the CD8+ cell response to SEB and toxic shock syndrome toxin-1 after Day 4 was revived by exogenous recombinant interleukin-2 (rIL-2) supplementation, suggesting that the consequent autocrine or paracrine secretion of IL-2 from the responding cells is essential for subsequent cell proliferation. SEB-induced cell proliferation was significantly suppressed by anti-CD11a (lymphocyte function-associated antigen-1; LFA-1, alpha-chain) monoclonal antibody, and the inhibitory effect was most obvious in 6-day cultured CD8+ lymphocytes. The results suggest that the lymphocyte response associated with the cell-to-cell copresentation of superantigens involves LFA-1 molecules as an accessory factor, particularly in CD8+ lymphocytes.

Antibodies, Monoclonal↗
PubMed1996

Generic prescribing for epilepsy. Is it safe?

Generic prescribing for epilepsy remains controversial. This study aimed to ascertain if a change occurred in the incidence of seizures or side-effects when a different pharmaceutical manufacturer's version of the same antiepileptic drug was taken (a 'switch'). Forty general practices with a list size of 350 168 were recruited. They identified 2285 people being treated for epilepsy with either carbamazepine, phenytoin or sodium valproate. A questionnaire was sent to the people with epilepsy. Those who recalled taking a different pharmaceutical manufacturer's supply of the same antiepileptic drug over the last 2 years were interviewed by their practice if they reported a problem with the control of their epilepsy after a 'switch'. One thousand, three hundred and thirty-three (58.8%) people with epilepsy responded: 251 (18.7%) had experienced a 'switch', 27 (10.8%) reported 'validated' problems; 25 (9.9%) reported unproven problems; 22 (8.8%) reported problems, but follow-up was incomplete; 177 (70.5%) reported no problems. This study suggests that money saved by generic prescribing is outweighed by negative health gain for the person with epilepsy, increased work in general practice, and increased social costs.

Adult↗
PubMed1996

Human T lymphotropic virus type II (HTLV-II): epidemiology, molecular properties, and clinical features of infection.

Human T lymphotropic virus, type II (HTLV-II), infection has been shown to be endemic in a number of American Indian populations, and high rates of infection have also been documented in intravenous drug abusers in urban areas throughout the world. Although the role of HTLV-II in human disease has yet to be clearly defined, there is accumulating evidence that like HTLV-I, infection may also be associated with rare lymphoproliferative and neurological disorders. In this article we review and summarize the epidemiology, molecular properties and clinical features of HTLV-II infection.

Amino Acid Sequence↗
PubMed1996

mtDNA variation indicates Mongolia may have been the source for the founding population for the New World.

mtDNA RFLP variation was analyzed in 42 Mongolians from Ulan Bator. All four founding lineage types (A [4.76%], B [2.38%], C [11.9%], and D [19.04%]) identified by Torroni and colleagues were detected. Seven of the nine founding lineage types proposed by Bailliet and colleagues and Merriwether and Ferrell were detected (A2 [4.76%], B [2.38%], C1 [11.9%], D1 [7.14%], D2 [11.9%], X6 [16.7%], and X7 [9.5%]). Sixty-four percent of these 42 individuals had "Amerindian founding lineage" haplotypes. A survey of 24 restriction sites yielded 16 polymorphic sites and 21 different haplotypes. The presence of all four of the founding lineages identified by the Torroni group (and seven of Merriwether and Ferrell's nine founding lineages), combined with Mongolia's location with respect to the Bering Strait, indicates that Mongolia is a potential location for the origin of the founders of the New World. Since lineage B, which is widely distributed in the New World, is absent in Siberia, we conclude that Mongolia or a geographic location common to both contemporary Mongolians and American aboriginals is the more likely origin of the founders of the New World.

DNA, Mitochondrial↗
PubMed1995

Human immunodeficiency virus type 1 reverse transcriptase: enhancement of activity by interaction with cellular topoisomerase I.

A number of studies have suggested that topoisomerase I (topo I) activity may be important in human immunodeficiency virus type 1 (HIV-1) replication. Specifically it has been reported that purified virus particles have topo I activity and that inhibitors of this enzyme can inhibit virus replication in vitro. We have investigated a possible association of HIV-1 gag proteins with topo I activity. We found that whereas the gag-encoded proteins by themselves do not have activity, the nucleocapsid protein p15 can interact with and enhance the activity of cellular topo I. Furthermore it could be demonstrated that topo I markedly enhanced HIV-1 reverse transcriptase activity in vitro and that this could be inhibited by the topo I-specific inhibitor camptothecin. The findings suggest that cellular topo I plays an important role in the reverse transcription of HIV-1 RNA and that the recruitment of this enzyme may be an important step in virus replication.

Base Sequence↗
PubMed1995

Differential effect of TGF-beta 1 on the in vitro activation of HTLV-I and the proliferative response of CD8+ T lymphocytes in patients with HTLV-I-associated myelopathy (HAM/TSP).

While considerable information is available on the pathogenesis of human T lymphotropic virus type I (HTLV-I)-associated myelopathy/tropical spastic paraparesis (HAM/TSP), fundamental questions remain unanswered. In particular the clinicopathological uniformity of the disorder among patients remains poorly understood. The potential role of TGF-beta as a preferential immune regulator in the CNS and the functional heterogeneity of TGF-beta has led us to assess the possible involvement of this cytokine in the pathogenic process. To investigate this, the modulatory effects of TGF-beta 1 on HTLV-I-induced in vitro phenomena were evaluated using fractionated lymphocytes from patients with HAM/TSP. It could be shown that the proliferative response of CD8+ cells against cultured and irradiated autologous CD4+ cells possessing HTLV-I antigens was significantly inhibited by TGF-beta 1. However, the in vitro activation of HTLV-I, which was evaluated by spontaneous proliferation of CD4+ cells, was unaffected by TGF-beta 1. The induction of intracytoplasmic HTLV-I antigens in cultured CD4+ cells was facilitated by TGF-beta 1 in a dose-dependent manner. These findings suggest that TGF-beta may have a critical role in localized viral activation within the CNS in patients with HAM/TSP.

Adult↗