If free speech costs lives that's a high price to pay.
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Biomedical subjects
Publications and source records attributed to R A Weiss.
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Castleman disease (CD) is a lymphoproliferative disorder of unknown etiology that is associated with the development of secondary tumors, including B-cell lymphoma. Human herpesvirus 8 (HHV-8) (Kaposi's sarcoma-associated herpesvirus) sequences have been described in some cases of multicentric Castleman disease (MCD). Using a monoclonal antibody against an HHV-8-latent nuclear antigen, we show that HHV-8 is specifically associated with a variant of MCD in which HHV-8-positive plasmablasts that show lambda light-chain restriction localize in the mantle zone of B-cell follicles and coalesce to form microscopic lymphomas in some cases. Furthermore, we show that the frank plasmablastic lymphoma that develops in patients with this plasmablastic variant of MCD is also positive for HHV-8 and lambda light chain. Plasmablastic lymphoma associated with MCD is a new disease entity associated with HHV-8 infection. (Blood. 2000;95:1406-1412)
BACKGROUND: The goal of laser or flashlamp photoepilation is to produce long-term, cosmetically significant hair removal. We document the long-term efficacy achieved with an intense pulsed light source for photoepilation. DESIGN: Prospective study comparing long-term results of single vs multiple treatments, and effects of anatomic site and skin type on efficacy of photoepilation with a device emitting broad-spectrum, noncoherent (nonlaser) radiation from 550- to 1200-nm wavelengths, in macropulses divided into 2 to 5 minipulses. SETTING: Private dermatology practice. PATIENTS: Thirty-four patients (8 men, 26 women) with hirsutism. INTERVENTIONS: Parameters for the study were wavelength of 615 to 695 nm, pulse duration of 2.6 to 3.3 milliseconds, fluence of 34 to 42 J/cm(2), 10 x 45-mm exposure field, and application of 1 degrees C cooling gel. MAIN OUTCOME MEASURES: Hair removal efficiency, calculated as percentage ratio of the number of hairs present compared with baseline counts, and patient satisfaction questionnaire completed at last follow-up. RESULTS: The mean hair removal efficiency achieved was 76% after a mean of 3.7 treatments. More than 94% of the sites reached mean hair removal efficiency values greater than 50%. Hair removal efficiency was not significantly related to skin type, hair color, anatomic site, or number of treatments. Side effects were mild and reversible and occurred in a minority of patients (hyperpigmentation in 3 and superficial crusting in 2). CONCLUSIONS: Our data document the long-term clinical efficacy of intense pulsed light source-induced hair removal in light and dark skin phenotypes. Maximal photoepilation was achieved from the initial 1 to 3 treatments; only a small added benefit was seen after more treatments.
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Since the Human Immunodeficiency Virus was first isolated in 1983, we have come to know it in exquisite detail. Yet we still do not understand sufficiently how it causes disease. Neither do we know why chimpanzees and some African monkeys, which are the natural reservoir of the precursors of HIV-1 and HIV-2, can harbour similar levels of virus without becoming ill. Our knowledge of the replication cycle of HIV as a retrovirus has been pivotal in the development of antiviral drugs. Our knowledge of the cellular tropism and cell surface receptors exploited by the virus help to explain the pattern of immune deficiency, wasting and dementia that make up the clinical dimensions of AIDS. The extraordinary rate of genetic and phenotypic evolution of the virus - both within the infected individual and across the worldwide pandemic - partially explains why no vaccine constructs to date have been successful. HIV comprises just 9 genes but represents one of humanity's most formidable foes.
BACKGROUND: Tissue necrosis after sclerotherapy has been observed, but is unexplained. OBJECTIVE: To present the complication of extensive tissue necrosis following high-concentration sclerotherapy for varicose veins. METHODS: Cases coming to the attention of the authors are presented briefly with commentary and discussion to explain the mechanisms of tissue destruction. RESULTS: Although the complication of extensive tissue necrosis has been ascribed to intra-arterial injection, in fact, careful study of the cases described here shows that intravenous injection was present in each case. A theory of distribution of the sclerosant into the arterial arborization is proposed. This theory would explain the distribution of sclerosant into the arterial tree and would also explain the causation of extensive tissue necrosis. Mention is made of experimental work in which intra-arterial injection was not the mechanism of causation of tissue necrosis. CONCLUSION: Extensive tissue necrosis following high-concentration sclerotherapy may be rare, but its occurrence is serious and its treatment may be incomplete.
BACKGROUND: Effective treatment of poikiloderma of Civatte combines elimination of both the vascular and pigmented components simultaneously. A broad spectrum, noncoherent, intense pulsed light (IPL) source delivers multiple wavelengths with software controlled pulse durations and sequencing, which permits treatment of both vascular and pigmented lesions simultaneously. OBJECTIVE: To determine response and side effects of poikiloderma of Civatte of the neck and chest when treated by IPL. METHODS: One hundred and thirty-five patients randomly selected with typical changes of poikiloderma of Civatte on the neck and/or upper chest were treated with one to five treatments using IPL. RESULTS: Clearance of more than 75% of telangiectasias and hyperpigmentation comprising poikiloderma was observed. The incidence of side effects was 5%, including pigment changes. In many cases, improved skin texture was noted both by physician and patient. CONCLUSION: IPL is an effective mode of therapy for poikiloderma of Civatte. It offers a reduction of pigment and telangiectasias with a low risk profile. Additional benefits include subjective changes of improvement in skin texture.
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BACKGROUND: Intense pulsed light (IPL), utilizing noncoherent yellow, red, and near-infrared wavelengths can be used to treat telangiectasias. In order to circumvent epidermal heating and allow greater fluence to be delivered safely, a new device that circulates water around the IPL crystal in contact with the skin to provide continuous cooling at 1 degrees C-4 degrees C range was developed. OBJECTIVE: To observe the effects of contact cooling on IPL treatment of leg telangiectasias. METHODS: A total of 25 patients were treated using two similar sites of matted telangiectasias on the leg, one site was treated without epidermal cooling and the other with the epidermal cooling crystal collar device. Results were evaluated by comparison with pretreatment photographs at 1 month. At one treatment center, a crossover was performed at the 1-month visit in which the non-E3C site was treated by cooling. Parameters consisted of a 570 nm filter, coupled pulses of 2-2.5 msec/6-7 msec with a 10-msec delay with fluences of 38-40 J. On the site receiving contact cooling the fluence was increased by 10% (4 J/mm2). Sites were graded worse, unchanged, or improved (RAW) or on a numerical scale of 1-4 (NSS). RESULTS: Compared to the contact cooling sites, uncooled sites showed 7 were improved, 5 were unchanged, and 3 were worsened, but cooled sites showed 10 were improved, 5 were unchanged, and none were worsened (P<.05). The grading scale on 10 patients revealed a mean improvement of 1.7 for noncooled sites and 2.7 for cooled sites (P<.001). For crossover treatment, eight noncooled sites (unchanged or worsened) were subsequently treated with cooling, demonstrating six improved (P<.001) and two with no change. Less erythema and edema was noted at all cooled sites. Furthermore, pain was significantly reduced with cooling (P<.003). Epidermal injury involving hyper- or hypopigmentation, crusting, or vesiculation was not observed in any of the cooled sites, but was recorded in three of the noncooled sites. CONCLUSIONS: These data indicate that continuous epidermal cooling with IPL allows delivery of higher fluences with less pain and fewer side effects. Efficacy is significantly improved using the coupled short pulse/long pulse protocol. An additional benefit is that IPL treatment becomes less operator dependent because the chilled crystal may be placed directly in contact with the skin.
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Human herpesvirus 8 (HHV-8), also known as Kaposi's sarcoma associated herpesvirus (KSHV), has been shown to be the causative agent for Kaposi's sarcoma (KS) and to be more prevalent in populations or risk groups at increased risk for KS. HHV-8 infection is rare in children from the US and the UK, but has been reported in African children. In this study we examine HHV-8 infection in children from Italy, a country with an elevated prevalence of HHV-8 in adults and high socio-economic conditions.
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The natural history of type D simian retrovirus (SRV) infection is poorly characterized in terms of viral load, antibody status, and sequence variation. To investigate this, blood samples were taken from a small cohort of mostly asymptomatic cynomolgus macaques (Macaca fascicularis), naturally infected with SRV type 2 (SRV-2), some of which were followed over an 8-month period with blood taken every 2 months. Provirus and RNA virus loads were obtained, the samples were screened for presence of antibodies to SRV-2 and neutralizing antibody titers to SRV-2 were assayed. env sequences were aligned to determine intra- and intermonkey variation over time. Virus loads varied greatly among cohort individuals but, conversely, remained steady for each macaque over the 8-month period, regardless of their initial levels. No significant sequence variation was found within an individual over time. No clear picture emerged from these results, which indicate that the variables of SRV-2 infection are complex, differ from those for lentivirus infection, and are not distinctly related to disease outcome.
Human T-cell leukemia virus type 1 (HTLV-1) is the etiologic agent of adult T-cell leukemia/lymphoma (ATLL), HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP), and other diseases. The mechanisms of virus pathogenesis are still obscure. The occurrence of defective proviruses in HTLV-1-infected cell lines and the peripheral blood mononuclear cells (PBMC) of infected individuals is a frequent feature of virus infection. We detected defective proviruses with large internal deletions in PBMC from ATLL and HAM/TSP patients and in asymptomatic HTLV-1 carriers. Seventeen PCR-amplified defective proviruses were sequenced, and three types of deletions were found. Besides truncated MA and the 5' end of the genome, truncated CA, truncated SU, and more frequently truncated TM linked to the pX region were detected. Reverse transcription-PCR analysis of PBMC from ATLL patients and asymptomatic carriers also revealed RNA transcripts with large internal deletions. Analysis of two RT-PCR cDNA clones confirmed a Gag-TM-pX structure of the transcripts. Most defective proviruses contained numerous internal stop codons, but some were capable of coding for the truncated MA linked to a variable out-of-frame peptide. Cloned defective proviruses with long open reading frames were subjected to in vitro transcription-translation followed by radioimmunoprecipitation, which showed expression of chimeric proteins between 8 and 12 kDa. Possible roles of defective proviruses and chimeric proteins are discussed, although there is no firm association with pathogenesis.
Retroviruses are transmitted in two distinct ways: as infectious particles and as 'endogenous' proviral DNA integrated in the germ line of the host. Modern infectious viruses such as HIV-1 and HIV-2 recently infected mankind from chimpanzee and simian hosts, whereas human endogenous retroviral genomes have been present throughout old world primate evolution. Human T-cell leukemia viruses (HTLV-1 and II) have a much older human provenance than HIV, although new zoonoses from simians may also occur. We have recently characterized new retroviruses in pigs and humans. Porcine endogenous retroviral (PERV) genomes are carried in chromosomal DNA but can be activated to produce virions that are infectious for human cells, which has raised concern over human xenotransplantation using pig tissues. Human retrovirus 5 (HRV-5) is detected as an exogenous genome in association with arthritis and systemic lupus erythematosus.
We examined the transcription and splicing of open reading frames (ORFs) 71 (K13)-74 of human herpesvirus-8 (HHV-8) in the primary effusion lymphoma cell line BCP-1 (latently infected with HHV-8), using a combination of NORTHERN blot analysis, RT-PCR, and rapid amplification of cDNA ends (PCR-RACE). The three genes encoded by ORFs 71, 72, and 73 [viral FLICE inhibitory protein (v-FLIP), v-cyclin, latent nuclear antigen (LNA)] are transcribed from a common transcription start site in BCP-1 cells uninduced (latent) or induced (lytic) with n-butyrate. The resulting transcript is spliced to yield a 5.32-kb message encoding LNA, v-cyclin, and v-FLIP and a 1.7-kb bicistronic message encoding v-cyclin and v-FLIP. The two genes encoded by ORFs K14 and 74 (v-Ox2 and v-GPCR) are transcribed as a 2.7-kb bicistronic transcript that is induced with n-butyrate. A small (149-bp) intron is spliced from the intragenic noncoding region immediately before the v-GPCR initiating codon. Examination of sequence elements in the promoter of the LNA/v-cyclin/v-FLIP operon revealed TAATGARAT and Octamer binding motifs characteristic of herpesvirus immediate-early genes. Sequence elements in the v-Ox2/v-GPCR promoter included AP1 and Zta-like (EBV Zebra transactivator) binding motifs consistent with the n-butyrate induction of this operon.