Biomedical subjects
R A Weiss
Publications and source records attributed to R A Weiss.
Transcriptional analysis of human herpesvirus-8 open reading frames 71, 72, 73, K14, and 74 in a primary effusion lymphoma cell line.
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.
Distribution of human herpesvirus-8 latently infected cells in Kaposi's sarcoma, multicentric Castleman's disease, and primary effusion lymphoma.
Human herpesvirus 8 (HHV-8, also called KSHV) is linked to the etiopathogenesis of Kaposi's sarcoma (KS), multicentric Castleman's disease (MCD), and primary effusion lymphoma (PEL). The universal presence of HHV-8 in early KS has not yet been shown. We used a mAb (LN53) against latent nuclear antigen-1 (LNA-1) of HHV-8 encoded by ORF73 to study the distribution of the cell types latently infected by HHV-8 in patch, plaque, and nodular KS, MCD, and PEL. In early KS, HHV-8 is present in <10% of cells forming the walls of ectatic vessels. In nodular KS, HHV-8 is present in cells surrounding slit-like vessels and in >90% of spindle cells, but not in normal vascular endothelium. In addition, HHV-8 colocalizes with vascular endothelial growth factor receptor-3 (VEGFR-3), a marker of lymphatic and precursor endothelium. In early KS lesions, VEGFR-3 is more extensively expressed than LNA-1, indicating that HHV-8 is not inducing the proliferation of VEGFR-3-positive endothelium directly. In MCD, HHV-8 is present in mantle zone large immunoblastic B cells. No staining for LNA-1 is seen in samples from multiple myeloma, prostate cancer, and angiosarcoma, supporting the absence of any etiological link between these diseases and HHV-8.
Two types of HTLV-1 particles are released from MT-2 cells.
The MT-2 cell line transformed by human T-cell leukemia virus type 1 (HTLV-1) contains one complete provirus and seven defective proviruses. Four defective genomes have an identical structure (LTR-MA-deltaCA-pX-LTR) with an open reading frame that spans from MA to pX, giving rise to a 3.4-kb (24S) RNA transcript encoding a chimeric Gag-pX protein, p28. MT-2 cells release two distinct types of virions. The major "classic" type of particle has a buoyant density of 1.155-1.16 g/cm3 and contains the standard HTLV-I structural proteins and reverse transcriptase (RT). In addition, about 5% of particles are "light," approximately 1.12 g/cm3, and contain p28, RT activity, and the 3.4-kb RNA transcript. RT-PCR and in vitro translation indicate that some of the classic HTLV-1 particles package 3.4-kb RNA as well as full-length 8.5-kb RNA. In addition to matrix features, the p28 protein has a motif resembling a zinc finger at the C-terminal, pX0 region, which may play a role in the assembly of the defective light virions.
From Pan to pandemic.
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Degradation of p27(Kip) cdk inhibitor triggered by Kaposi's sarcoma virus cyclin-cdk6 complex.
The Kaposi's sarcoma-associated human herpesvirus 8 (KSHV/HHV8) encodes a protein similar to cellular cyclins. This cyclin is most closely related to cellular D-type cyclins, but biochemically it behaves atypically in various respects. Complexes formed between the viral cyclin and the cyclin-dependent kinase subunit, cdk6, can phosphorylate a wider range of substrates and are resistant to cdk inhibitory proteins. We show here that the KSHV-cyclin-cdk6 complex phosphorylates p27(Kip) on a C-terminal threonine that is implicated in destabilization of this cdk inhibitor. Expression of the viral cyclin in tissue culture cells overcomes a cell cycle block by p27(Kip). However, full cell-cycle transit of these cells appears to depend on C-terminal phosphorylation of p27(Kip) and seems to involve transactivation of other cellular cyclin-dependent kinases. A p27(Kip)-phosphorylating cdk6 complex exists in cell lines derived from primary effusion lymphoma and in Kaposi's sarcoma, this indicating that virally induced p27(Kip) degradation may occur in KSHV-associated tumours.
Treatment of port-wine stains with a noncoherent pulsed light source: a retrospective study.
OBJECTIVE: We investigated whether a noncoherent intense pulsed light source (IPLS) would be effective in therapy of port-wine stains (PWSs). DESIGN: To evaluate the efficacy in treatment of PWSs with IPLS, a retrospective study was initiated. SETTING: The data were collected by physicians working in private practices and departments of university hospitals and medical centers, respectively. PATIENTS: A total of 37 randomly selected patients with a total of 40 PWSs were included in the study. Clinical PWS characteristics recorded were color and location of the PWS. INTERVENTIONS: All patients were treated with IPLS. MAIN OUTCOME MEASURES: Data collected included treatment parameter (filters, pulse duration, fluence, and pulse sequencing), percentage of clearance, and side effects (purpura, blisters, crusting, altered pigmentation, and scarring). RESULTS: Good and complete (70%-100%) clearance was achieved in 28 of 40 PWSs treated with IPLS. The average number of treatment sessions in PWSs reaching 100% clearance included 4.0 for pink PWSs and 1.5 for red PWSs. The average number of sessions for purple PWSs reaching good clearance (70%-99%) was 4.2 sessions. Parameters used most frequently were 515- and 550-nm cut-off filters, pulse duration of 2.5 to 5.0 milliseconds, and fluences of 24 to 60 J/cm2. Side effects included purpura in 133 (76%), superficial blisters in 14 (8%), and crusting in 35 (20%). Transient pigmentation changes were seen in 10.8% of patients (hypopigmentation in 3 [8.1%], hyperpigmentation in 1 [2.7%]). No scarring was observed. CONCLUSION: Intense pulsed light source presents an effective and safe method for treating PWSs, especially purple PWSs.
Hair removal with a non-coherent filtered flashlamp intense pulsed light source.
BACKGROUND AND OBJECTIVE: To evaluate the effects on disruption of hair growth of the non-coherent filtered flashlamp intense pulsed light (IPL) source. MATERIALS AND METHODS: Twenty-eight sites on 23 patients with Fitzpatrick type I-III were enrolled using a single treatment IPL followed for three months post-treatment. Another 56 on 48 patients with Fitzpatrick skin types I-V randomly enrolled for two treatments one month apart and followed for six months. STUDY DESIGN: Prior to beginning treatment and at each follow-up visit hair counts were obtained by averaging three 1-cm2 areas on a clear acetate template placed over the skin. Repeat hair counts and photographs were obtained at 2, 4, 8, and 12 weeks for the single treatment protocol and at additional 4, 5, and 6 months for the double treatment protocol. Parameters utilized were a 2.8-3.2 millisecond pulse duration typically for three pulses with thermal relaxation intervals of 20-30 milliseconds with a total fluence of 40-42 J/cm2. RESULTS: For the double treatment protocol hair clearance of 64% was achieved immediately following the second treatment. By week 8 reduction of hair counts was 42%. At 6 months, hair counts were reduced by 33%. CONCLUSIONS: Non-coherent IPL is an effective modality for long-term hair removal. IPL is safe with minimal side effects of epidermal injury or pigmentation change.
Periorbital skin resurfacing using high energy erbium:YAG laser: results in 50 patients.
OBJECTIVE: To evaluate Erbium:YAG regional periorbital laser resurfacing clinically and histologically. STUDY DESIGN/MATERIALS AND METHODS: Photographic evaluation before and after Erbium:YAG resurfacing with histologic evaluation of depth of injury. SETTING: Group private single specialty practice. PATIENTS: Fifty patients in the age range of 35-62 years, Fitzpatrick skin types I-III were treated using Erbium:YAG for regional resurfacing of periorbital rhytides. OUTCOME MEASURES: Patients were seen at days 1, 2, 3, 7, 14, 28, and at six months and one year. Photographs were obtained prior to application of topical anesthesia and were utilized to judge improvement of rhytides at all time intervals. Additional photographs were taken at each follow-up visit and the results judged by an independent investigator. Results were graded into five categories at all treatment intervals: no improvement, mild (grade 1: up to 25%), moderate (grade 2: 25-50%), good (grade 3: 50-75%, or excellent (grade 4: 75-100%). For histologic evaluation of depth of ablation and thermal injury one, two, and three passes at 21.2 J/cm2 were performed on four patients. RESULTS: Re-epithelization in the periorbital region was rapid with a mean duration of 2.65 days. Erythema ranged from a longest of six weeks to the shortest of seven days with a mean duration of 15.4 days. Evaluation of clinical results revealed that at two weeks mean improvement was 2.15 (between moderate and good). At four weeks further improvement was noted with a mean of 2.62. By six months, mean improvement score increased to 2.94. Minimal further improvement was noted between six months and one year with a mean improvement score of 3.02 (good to excellent). Histology revealed complete removal of the epidermis with one to three passes. Dermal ablation of 5-10 microns accompanied by small increases (5-10 microns) in dermal thermal injury occurred with each subsequent pass. CONCLUSIONS: We conclude that high energy Erbium:YAG periorbital resurfacing is a safe and effective modality which achieves substantial therapeutic effect. Most patients achieve approximately 75% improvement. Erythema fades quickly, reepithelization is rapid and side effects are minimal.
Detection of human retrovirus 5 in patients with arthritis and systemic lupus erythematosus.
OBJECTIVE: To examine whether human retrovirus 5 (HRV-5) infection is associated with autoimmune rheumatic disease. METHODS: DNA from patients with various disorders including inflammatory diseases and from normal subjects was tested by nested polymerase chain reaction (PCR) for HRV-5 proviral DNA. Positive results were confirmed by DNA sequencing. RESULTS: HRV-5 proviral DNA was detected in 53% of synovial samples from arthritic joints, in 12% of blood samples from patients with rheumatoid arthritis (RA), and in 16% of blood samples from patients with systemic lupus erythematosus. In contrast, it was not detectable by PCR of affected tissues from patients with several other autoimmune diseases and was found in only 1 of >200 tissue specimens obtained at autopsy from non-RA patients. Sequence analysis of the amplified viral segment showed genetic variation between samples with maintenance of the open reading frame, typical of a replicating infectious retrovirus. CONCLUSION: This is the first report of the frequent detection of HRV-5 in any disease. We propose that the possible involvement of HRV-5 in autoimmune and rheumatic disease should be investigated further.
Retroviruses: ancient and modern.
Retroviruses are transmitted in two distinct ways: as infectious virions and as 'endogenous' proviral DNA integrated in the germ line of their hosts. Modern infectious viruses such as HIV recently infected mankind from simian hosts, whereas human endogenous retroviral genomes have been present throughout old world primate evolution. Recently we have characterised novel retroviruses in humans and pigs. Human retrovirus 5 (HRV-5) is detected as an exogenous genome in association with arthritis and systemic lupus erythematosus. Porcine endogenous retroviruses (PERV) are carried in swine DNA but can be activated to produce virions that are infectious for human cells, which has implications for xenotransplantation. A brief account of HRV-5 and PERV is given here.
Peripheral nerve tumors of the orbit.
Neurofibromas and schwannomas are orbital neoplasms with similar clinical and radiologic features. Solitary or circumscribed neurofibromas and schwannomas demonstrate slow progressive growth with ocular displacement and are amenable to surgical resection. Plexiform and diffuse neurofibromas are diffusely infiltrative in the orbit and periocular region, they are difficult to resect, and they have a high rate of recurrence. Malignant peripheral nerve tumors are rare, but they have a very high rate of recurrence and a low 5-year survival rate because of extension through the superior orbital fissure to the midbrain region. This article describes the clinical and radiologic features of peripheral nerve sheath tumors.
Lentivirus tropism and pathogenesis.
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Scanning electron microscopy comparison of corneal epithelial removal techniques before photorefractive keratectomy.
PURPOSE: To evaluate and compare the most common epithelial removal techniques by scanning electron microscopy. SETTINGS: Beckman Laser Institute, University of California, Irvine, California, USA. METHODS: The epithelium was removed in both eyes of 5 Dutch belted rabbits by 1 of 5 techniques: blunt mechanical debridement (with a blunt spatula), sharp mechanical debridement (with a sharp scalpel blade), application of topical alcohol, and transepithelial removal with the excimer laser and with the rotary epithelial scrubber. The animals were immediately killed and corneal specimens prepared for scanning electron microscopy. The degree of corneal trauma and the completeness of epithelial cell removal with the 5 techniques were evaluated by comparing the regularity and smoothness of the resulting stromal surfaces. RESULTS: Epithelial removal with alcohol, the excimer beam, and the rotary epithelial scrubber produced a smoother, more uniform anterior stromal surface than blunt and sharp mechanical debridement. CONCLUSIONS: The smooth and uniform anterior stromal surface produced with the rotary epithelial scrubber, alcohol, and the laser beam may be preferable prior to photorefractive keratectomy.
Post-sclerotherapy compression: controlled comparative study of duration of compression and its effects on clinical outcome.
BACKGROUND: Although much has been published on the effects of compression on the venous system, relatively few studies address the duration of compression following sclerotherapy of telangiectatic webs associated with reticular veins. OBJECTIVE: To perform a controlled study comparing the effects of different durations of compression following sclerotherapy of reticular veins and telangiectasias in similar locations. METHOD: This study consisted of a total of 40 patients, 30 patients who received compression therapy and 10 control patients who did not receive compression therapy. The compression group consisted of 10 in each of three duration groups: 3 days, 1 week, and 3 weeks. Patients were evaluated at 1 week, 2 weeks, 6 weeks, 12 weeks, and 24 weeks for degree of improvement and side effects. RESULTS: The three compression groups showed significantly greater improvement at 6 weeks (p = .004). There was a strong correlation between the length of time compression was applied and degree of improvement at 6 weeks, 12 weeks, and 24 weeks of clinical follow-up; r = .74, p = .0006, r = .59, p = .006, r = .66, p = .0001, respectively. The patients treated with compression for 3 days and 1 week had more improvement than the control patients while the patients treated for 3 weeks of continuous compression had the most improvement. In terms of side effects, the 1 week and 3 week compression groups experienced the least amount of post-sclerotherapy hyperpigmentation. CONCLUSIONS: Compression enhances the results following sclerotherapy in a statistically significant way and is directly correlated with duration of compression. Three weeks of continuous compression leads to the best results, although even 3 days of compression results in greater improvement than no compression. Compression leads to a statistically significant reduction of post-sclerotherapy hyperpigmentation.
Early clinical results with a multiple synchronized pulse 1064 NM laser for leg telangiectasias and reticular veins.
BACKGROUND: The 1064 nm wavelength penetrates tissue and blood vessels with little absorption by melanin. OBJECTIVE: To perform a study examining the effects of 1064 nm laser used in pulses from 4 msec to 16 msec on leg telangiectasias ranging in size from 0.5 to 3 mm. METHOD: In this initial trial, 50 sites on 30 patients were enrolled and treated with a multiple synchronized pulse laser at 1064 nm. The primary parameter utilized was a single 10-16 msec pulse. Improvement was judged by comparison of digital images at 1 month, 2 months, and 3 months posttreatment. Improvement was judged, based on size and number of vessels remaining. Side effects were noted as present or absent at each visit. RESULTS: Immediate contraction or darkening followed by urtication and visible total vessel closure as indicated by absence of blanching and visual elimination of the vessel border occurred in most of the treated sites. Two 3 mm diameter vessels were confirmed to be closed without flow by Duplex ultrasound visualization, using a 10 MHz transducer. Bruising from vessel rupture was seen in approximately 50% of the cases. No epidermal injury was noted in any sites, even in Fitzpatrick skin Types IV. At 3 months follow-up, 75% improvement was noted at treatment sites. CONCLUSIONS: Initial clinical results with a new multiple synchronized pulsed 1064 nm laser indicate that this longer wavelength supplied at pulses of up to 16 msec appears to be a valuable modality for immediate closure and subsequent elimination of leg ectatic veins. Epidermal injury is unlikely, as the near infrared wavelength has minimal interaction with melanin.
Clinical benefits of lightweight compression: reduction of venous-related symptoms by ready-to-wear lightweight gradient compression hosiery.
BACKGROUND: Medical-grade compression of class I (20-30 mmHg) and class II (30-40 mmHg) have been shown to be beneficial against venous hypertension or congestion. Relatively few studies address the effects of ready-to-wear (RTW) lightweight gradient compression pantyhose on venous symptoms. OBJECTIVE: To perform a study comparing the effects of two different compression RTW lightweight gradient compression stockings (8-15 mmHg and 15-20 mmHg) on the venous symptoms of flight attendants. METHOD: A prospective crossover trial of symptom evaluation in 19 flight attendants was performed in which participants rated their symptoms on a visual analog scale. During the initial phase, participants wore no compression for 2 weeks. They then wore 8-15 mmHg and 15-20 mmHg gradient compression support hose while flying over a 4-week period. Symptoms before and after wearing the gradient compression stockings were compared and statistically analyzed. RESULTS: Wearing of 8-15 mmHg gradient hose resulted in statistically significant improvement of discomfort (P < 0.01). Swelling, fatigue, aching, and tightness of the leg were all improved to a statistically significant degree (P < 0.01). For 15-20 mmHg gradient hosiery, symptoms were improved to a statistically significant or almost significant level. The difference between the 8-15 mmHg and 15-20 mmHg compression was not statistically significant. CONCLUSIONS: Use of lightweight (low compression) RTW gradient compression hosiery is very effective in improving symptoms of discomfort (P < 0.01), swelling (almost P < 0. 05), fatigue (P < 0.05), aching (P < 0.01), as well as leg tightness. Improvement of symptoms is statistically significant compared to no compression when hosiery was worn regularly during waking hours for 4 weeks.
Regarding corporate affiliation.
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