Frequency-Dependent Squeezing for Advanced LIGO.

The first detection of gravitational waves by the Laser Interferometer Gravitational-Wave Observatory (LIGO) in 2015 launched the era of gravitational-wave astronomy. The quest for gravitational-wave signals from objects that are fainter or farther away impels technological advances to realize ever more sensitive detectors. Since 2019, one advanced technique, the injection of squeezed states of light, is being used to improve the shot-noise limit to the sensitivity of the Advanced LIGO detectors, at frequencies above ∼50 Hz. Below this frequency, quantum backaction, in the form of radiation pressure induced motion of the mirrors, degrades the sensitivity. To simultaneously reduce shot noise at high frequencies and quantum radiation pressure noise at low frequencies requires a quantum noise filter cavity with low optical losses to rotate the squeezed quadrature as a function of frequency. We report on the observation of frequency-dependent squeezed quadrature rotation with rotation frequency of 30 Hz, using a 16-m-long filter cavity. A novel control scheme is developed for this frequency-dependent squeezed vacuum source, and the results presented here demonstrate that a low-loss filter cavity can achieve the squeezed quadrature rotation necessary for the next planned upgrade to Advanced LIGO, known as "A+."

Platelet factor XI: intracellular localization and mRNA splicing following platelet activation.

BACKGROUND: The structure and function of platelet factor XI (FXI) protein and the presence of F11 mRNA in platelets are controversial. Although platelets are anucleated cells they contain spliceosome components and pre-mRNAs. Three platelet proteins have been demonstrated to be spliced upon platelet activation. OBJECTIVE: To determine whether FXI is also spliced upon activation and to discern the localization of FXI in platelets. METHODS: Localization of FXI in platelets was assessed by confocal immunofluorescence staining. ELISA, chromogenic assay and western blot analyses were used to measure antigen levels, activity levels and size of FXI in platelets, respectively. Splicing patterns of F11 mRNA were assessed in three states of platelet activation: activated platelets, resting platelets and αIIbß3-integrin activated platelets. RESULTS: Platelet FXI was exhibited in platelet granules. Activated platelets exhibited higher levels of mature F11 mRNA and protein and lower levels of F11 pre-mRNA compared to resting or αIIbß3-integrin activated platelets. CONCLUSIONS: We confirmed the presence of FXI in platelets and showed that it is localized in granules but is not restricted to the same α-granule subtype as von-Willebrand factor and p-selectin. Our study also shows that F11 is present in platelets as pre-mRNA and is spliced upon platelet activation.

A unique case of rituximab-related posterior reversible encephalopathy syndrome in a heart transplant recipient with posttransplant lymphoproliferative disorder.

Rituximab is commonly used as a first line therapy to treat posttransplant lymphoproliferative disorders (PTLDs). It has also proved useful in the management of refractory antibody mediated graft rejection. We report an unusual case in which a heart transplant recipient being treated with rituximab for PTLD developed altered mental status, hallucinations and visual symptoms and magnetic resonance imaging (MRI) findings of symmetrical enhancement suggestive of posterior reversible leukoencephalopathy syndrome (PRES). Resolution of these clinical symptoms and radiological findings after discontinuation of therapy confirmed the diagnosis. This is the first case of PRES seen due to rituximab in a heart transplant recipient. Another unique feature of the case is the development of PRES after second cycle of rituximab as compared to prior reports in nonheart transplant patients in which the syndrome developed after first dose administration. The objective of this case report is to increase the awareness of this rare entity amongst immunocompromised transplant patients.

The future direction of the adult heart allocation system in the United States.

Ensuring equitable and fair organ allocation is a central charge of the United Network for Organ Sharing (UNOS) as the Organ Procurement and Transplantation Network (OPTN) through its contract with the Department of Health and Human Services (DHHS). The OPTN/UNOS Board initiated a reassessment of the current allocation system. This paper describes the efforts of the OPTN/UNOS Heart Subcommittee, acting on behalf of the OPTN/UNOS Thoracic Organ Transplantation Committee, to modify the current allocation system. The Subcommittee assessed the limitations of the current three-tiered system, outcomes of patients with status exceptions, emerging ventricular assist device (VAD) population, options for improved geographic sharing and status of potentially disenfranchised groups. They analyzed waiting list and posttransplant mortality rates of a contemporary cohort of patient groups at risk, in collaboration with the Scientific Registry of Transplant Recipients to develop a proposed multi-tiered allocation scheme. This proposal provides a framework for simulation modeling to project whether candidates would have better waitlist survival in the revised allocation system, and whether posttransplant survival would remain stable. The tiers are subject to change, based on further analysis by the Heart Subcommittee and will lead to the development of a more effective and equitable heart allocation system.

The Impact of the Preoperative Mental Health Component Summary (MCS) Score on Short-term Outcomes after Lumbar Fusion.

STUDY DESIGN: Retrospective cohort study. OBJECTIVE: The purpose of this study is to characterize the relationship between preoperative MCS and surgical outcomes after lumbar spine surgery including inpatient complications, length of stay, readmissions, and reoperations. SUMMARY OF BACKGROUND DATA: As the prevalence of mental health disorders in the United States increases, it is important to identify risks associated with poor mental health status in the surgical spine patient. The mental health component summary (MCS) of the Short Form-12 has been used extensively as an indication of a patient's mental health status and psychological well-being. METHODS: Adult patients older than or equal to 18 years who underwent primary one to three level lumbar fusion surgery at our academic medical institution from 2017 to 2021 were retrospectively identified. Preoperative MCS score was used to analyze outcomes in patients based on a cutoff (<45.6). A score >45.6 indicated better preoperative mental health and a score <45.6 indicated worse preoperative mental health. RESULTS: Patients with lower preoperative MCS scores had longer hospital stays (3.86 + 2.16 vs. 3.55 + 1.42 days, P=0.010) and were more likely to have inpatient renal complications (3.09% vs. 7.19%, P=0.006). Patients with lower preoperative MCS scores also had lower Activity Measure for Post-Acute Care (AM-PAC) scores (17.1 + 2.85 vs. 17.6 + 2.49, P=0.030). Ninety-day surgical readmissions, medical readmissions, and reoperations were not significantly different between groups (P>0.05). CONCLUSION: Our study suggests that patients with lower preoperative mental health scores (MCS < 45.6) were independently more likely to experience more renal complications and longer length of stay after primary lumbar fusion. Additionally, higher MCS scores may correlate with better postoperative mobility and daily activity scores. Nevertheless, long-term outcomes are not significantly different between patients of better or worse preoperative mental health.

A novel therapeutic approach to the treatment of scleroderma-associated pulmonary complications: safety and efficacy of combination therapy with imatinib and cyclophosphamide.

OBJECTIVE: Scleroderma-related interstitial lung disease (SSc-ILD) has limited therapeutic options due to unclear pathogenesis. Recently, PDGF receptor (PDGFR) amplification has been postulated to cause fibrosis. We hypothesized that a combination of immunosuppressive agents, e.g. cyclophosphamide (CYC) and imatinib (PDGFR inhibitor), might be useful for treating SSc-related ILD. Our objective was to evaluate the safety and efficacy of this combination therapy in scleroderma-related pulmonary disease. METHODS: Five patients with advanced SSc-ILD underwent comprehensive cardiopulmonary evaluation, followed by administration of oral imatinib (200 mg/day) and intravenous CYC (500 mg every 3 weeks). Safety was assessed by close monitoring of complete blood count, liver and cardiac functions. Efficacy was evaluated by measuring pulmonary functions at 6 and 12 months. RESULTS: Of the five patients in the study, four had severe and one had mild restrictive lung disease. All patients tolerated the combination treatment without myelosuppression, deterioration of liver functions or cardiac status. Only one patient had mild fluid overload requiring diuretics. Two patients completed 1 yr of treatment. Only the patient with mild restrictive lung disease showed improvement in pulmonary function. CONCLUSION: The combination of intravenous CYC and oral imatinib was well-tolerated without major side effects. Clinical improvement was seen in only the patient with mild restrictive disease. To our knowledge, this is the first study examining the safety, tolerability and efficacy of imatinib in combination with CYC in scleroderma-related pulmonary disease. Large prospective trials are needed to further determine optimal timing, dose and duration of this regimen.

The tumor-promoter phorbol ester (12-O-tetradecanoyl-phorbol-13-acetate), a potent aggregating agent for blood platelets.

The phorbol ester 12-0-tetradecanoyl-phorbol-13-acetate, a potent tumor-promoting agent, caused irreversible platelet aggregation when more than 0.02 microM was stirred with human citrated or heparinized platelet-rich plasma (PRP). With washed platelets, 1 nM was effective. The alcohol phorbol, which has little tumor-promoting activity, failed to cause platelet aggregation. With all but low concentrations of phorbol ester, aggregation was succeeded by a rapid phase. The latter was prevented or reduced by enzymes which destroy ADP and by aspirin, was associated with a change in platelet shape, and was presumably due to released ADP. At higher concentrations, only a rapid phase was seen, and these inhibitors were not effective. Low concentrations did not aggregate platelets in PRP containing sufficient EDTA or EGTA to chelate ionized calcium or in PRP from thrombasthenic patients; higher concentrations caused slight aggregation. Both the primary, non-ADP-dependent aggregation and the rapid ADP-dependent aggregation were markedly inhibited by substances which increase cyclic AMP, metabolic inhibitors, and the sulfhydryl inhibitor N-ethylmaleimide. Phorbol ester reduced platelet cyclic AMP only when it had been previously elevated by prostaglandin E(1). 1 microM did not release beta-glucuronidase, lactic dehydrogenase, or inflammatory material from platelets in 4-5 min despite marked aggregation, but liberated all three in 30 min. The possibility is discussed that low phorbol ester concentrations cause primary aggregation by a direct action on platelet actomyosin.

Gamma-ray measurements of a soviet cruise-missile warhead.

A portable germanium detector was used to detect gamma-ray emissions from a nuclear warhead aboard the Soviet cruiser Slava. Measurements taken on the missile launch tube indicated the presence of uranium-235 and plutonium-239-the essential ingredients of nuclear weapons. With the use of this equipment, these isotopes probably could have been identified at a distance of 4 meters from the warhead. Such inspections do not reveal detailed information about the design of the warhead.

LIGO: The Laser Interferometer Gravitational-Wave Observatory.

The goal of the Laser Interferometer Gravitational-Wave Observatory (LIGO) Project is to detect and study astrophysical gravitational waves and use data from them for research in physics and astronomy. LIGO will support studies concerning the nature and nonlinear dynamics of gravity, the structures of black holes, and the equation of state of nuclear matter. It will also measure the masses, birth rates, collisions, and distributions of black holes and neutron stars in the universe and probe the cores of supernovae and the very early universe. The technology for LIGO has been developed during the past 20 years. Construction will begin in 1992, and under the present schedule, LIGO's gravitational-wave searches will begin in 1998.

Impact of Baseline Mitral Regurgitation on Postoperative Outcomes After Left Ventricular Assist Device Implantation as Destination Therapy.

BACKGROUND: Currently, there are no guidelines for management of moderate to severe mitral regurgitation (MR) in patients undergoing left ventricular assist device (LVAD) implantation. The present study aimed to investigate the impact of baseline MR on short and midterm survival in patients who had LVAD as destination therapy (DT). METHODS: The DT-LVAD patients were classified into 2 groups based on baseline MR status: ≥ moderate MR and < moderate MR. Baseline clinical characteristics and post-LVAD implant adverse events were compared. Unadjusted mortality rates at 30 days, 1 year, and 2 years were analyzed. RESULTS: Of 91 patients studied, 62 (68%) had ≥ moderate MR before LVAD implantation; ≥ moderate MR patients had a higher incidence of concomitant pulmonary disease (11% vs 0%; P = .001) and ≥ moderate tricuspid regurgitation (55% vs 23%, P = .004) than < moderate MR patients. Other baseline clinical characteristics were similar in both groups. Post-LVAD adverse events did not differ between the 2 groups. Survival rates at 30 days, 1 year, and 2 years for both groups (≥ moderate MR vs < moderate MR) were 90% vs 100% (P = .03), 63% vs 90% (P = .001), and 52% vs 83% (P = .002), respectively. On multivariable analysis, age, female sex, ≥ moderate tricuspid regurgitation, and ≥ moderate MR at baseline were found to be independent predictors of overall all-cause mortality. Overall survival was significantly lower in the ≥ moderate MR group than the < moderate MR group (log-rank test, P = .03). CONCLUSION: In DT LVAD patients, ≥ moderate MR is common and is associated with worse survival at both short and midterm follow-up.

Surgical management of aortic valve disease in elderly patients with and without coronary artery disease: influence on quality of life.

AIM: The feasibility of coronary artery bypass grafting (CABG) concomitant with aortic valve replacement (AVR) is well established. However, its impact on long-term patient-perceived quality of life (QoL) in the elderly remains undefined. METHODS: Retrospective analysis was conducted on 866 patients 65 years of age and over who underwent AVR between October 1976 and December 1999 with a Carpentier-Edwards porcine bioprosthesis. This cohort was divided between those who underwent isolated AVR (n=438) and those with AVR and concomitant CABG (AVR+CABG; n=428). Mean age was 77.0+/-6.1 years (range, 65 to 91) in the AVR group and 78.2+/-5.5 years (range, 65 to 93) in the AVR+CABG group. QoL was assessed with the Short Form-36 health survey for survivors at follow-up, which was 97% complete. RESULTS: Operative mortality (OM) was 6.2% (27/438) for the AVR group and 8.9% (38/428) for the AVR+CABG group (P=0.130). The occurrence of hospital complications (P=0.162) and postoperative length of stay (P=0.980) was similar for the 2 groups. Actuarial survival at 10 years was 37.1+/-3.4% for AVR and 38.7+/-4% for AVR+CABG patients (P=0.088). On multivariate analyses, CABG was not a predictor of either OM or long-term survival. QoL was similar for the 2 groups on the summary components: physical health (39.4+/-11.4 versus 40.2+/-12.1; P=0.461) and mental health (50.2+/-10.8 versus 51.9+/-10.1; P=0.103). CONCLUSIONS: Despite the presence of severe coronary artery disease, CABG preserved the long-term QoL in elderly patients undergoing AVR.

Clonal T-large granular lymphocyte proliferation in solid organ transplant recipients.

Large granular lymphocytic (LGL) leukemia is a rare disorder, usually caused by clonal proliferation of CD3+ CD57+ T-LGL cells. T-cell clonality is confirmed by rearrangements of the T-cell receptor (TCR) gene. Characteristic features of T-LGL leukemia include neutropenia, anemia, and constitutional symptoms such as fatigue. Many solid organ transplant recipients experience similar symptoms and have neutropenia and anemia often attributed to immunosuppressive therapy. The purpose of this study was to determine the prevalence of T-LGL proliferation in solid organ transplant recipients and demonstrate its association with leukopenia and anemia. Twenty-three cardiac and renal transplant patients were evaluated by peripheral smear examination, flow cytometry, and TCR gene rearrangement study by polymerase chain reaction. Ten of 14 (71%) cardiac transplant patients and 4 of 9 (44%) renal transplant patients, without evidence of either allograft rejection or a viral syndrome, were found to have clonal expansion of T-LGL cells. Constitutional symptoms were present in 30% of these patients. Anemia of <10 g/dL was seen in 75% of renal transplant and 10% of cardiac transplant patients. None of these patients had significant neutropenia defined as absolute neutrophil count of 1500 mu/L. Most of the patients did not require any specific therapeutic intervention. Although TCR gene rearrangement is considered a hallmark of T-LGL leukemia, we believe that this monoclonality is not a true form of posttransplant lymphoproliferative disorder. Constant antigenic stimulus from the allograft may be the underlying etiology of clonal expansion and may contribute to cytopenias and fatigue seen in transplant patients.

Improved survival with statins, angiotensin receptor blockers, and steroid weaning after heart transplantation.

Various immunosuppressive and adjunctive pharmacological regimens exist for cardiac transplantation, though the associations between these regimens and long-term survival are unclear. We reviewed demographic, clinical, and pharmacological data from 220 consecutive adult heart transplant recipients between 1986 and 2003 who survived beyond 3 months. Immunosuppression was cyclosporine-based (n=94) or tacrolimus-based (n=126), and 104 patients were weaned off steroids (all receiving tacrolimus). Covariates of mortality were assessed in a Cox proportional hazards analysis. The mean age was 5.2+/-13 years. Survival was 96%, 88%, and 81% at 1, 3, and 5 years, respectively. Significant covariates associated with mortality included pretransplant diabetes mellitus (hazard ratio [HR] 2.83, 95% confidence interval [CI] 1.45 to 5.04), black race (HR 1.41, 95% CI 1.01 to 1.94), higher pretransplant creatinine clearance (HR 0.99, 95% CI 0.98 to 1.00), steroid withdrawal (HR 0.60, 95% CI 0.39 to 0.85), and exposure to a statin (HR 0.53, 95% CI 0.40 to 0.70) or an angiotensin receptor blocker (HR 0.50, 95% CI 0.20 to 0.95) after transplantation. Treatment with a statin, an angiotensin receptor blocker, and steroid withdrawal were each associated with improved survival in heart transplant recipients. These findings warrant prospective study, with specific emphasis on identifying the clinical effects of these medications in transplant recipients.

An allosteric disulfide bond is involved in enhanced activation of factor XI by protein disulfide isomerase.

Essentials Reduction of three disulfide bonds in factor (F) XI enhances chromogenic substrate cleavage. We measured FXI activity upon reduction and identified a bond involved in the enhanced activity. Reduction of FXI augments FIX cleavage, probably by faster conversion of FXI to FXIa. The Cys362-Cys482 disulfide bond is responsible for FXI enhanced activation upon its reduction. SUMMARY: Background Reduction of factor (F) XI by protein disulfide isomerase (PDI) has been shown to enhance the ability of FXI to cleave its chromogenic substrate. Three disulfide bonds in FXI (Cys118-Cys147, Cys362-Cys482, and Cys321-Cys321) are involved in this augmented activation. Objectives To characterize the mechanisms by which PDI enhances FXI activity. Methods FXI activity was measured following PDI reduction. Thiols that were exposed in FXI after PDI reduction were labeled with 3-(N-maleimidopropionyl)-biocytin (MPB) and detected with avidin. The rate of conversion of FXI to activated FXI (FXIa) following thrombin activation was assessed with western blotting. FXI molecules harboring mutations that disrupt the three disulfide bonds (C147S, C321S, and C482S) were expressed in cells. The antigenicity of secreted FXI was measured with ELISA, and its activity was assessed by the use of a chromogenic substrate. The effect of disulfide bond reduction was analyzed by the use of molecular dynamics. Results Reduction of FXI by PDI enhanced cleavage of both its chromogenic substrate, S2366, and its physiologic substrate, FIX, and resulted in opening of the Cys362-Cys482 bond. The rate of conversion of FXI to FXIa was increased following its reduction by PDI. C482S-FXI showed enhanced activity as compared with both wild-type FXI and C321S-FXI. MD showed that disruption of the Cys362-Cys482 bond leads to a broader thrombin-binding site in FXI. Conclusions Reduction of FXI by PDI enhances its ability to cleave FIX, probably by causing faster conversion of FXI to FXIa. The Cys362-Cys482 disulfide bond is involved in enhancing FXI activation following its reduction, possibly by increasing thrombin accessibility to FXI.

De novo immunosuppression with sirolimus and tacrolimus in heart transplant recipients compared with cyclosporine and mycophenolate mofetil: a one-year follow-up analysis.

BACKGROUND: Limited data exist regarding the safety and efficacy of sirolimus in combination with a calcineurin inhibitor in heart transplant recipients. METHODS: From January 2001 to June 2002, 31 de novo heart transplant recipients (treatment group) received a combination of sirolimus, tacrolimus, low-dose rabbit antithymocyte globulin, and glucocorticoids. Outcomes, such as actuarial survival, rate of rejection, incidence of infection, probability of developing diabetes mellitus, renal function, platelet and white blood cell counts, and incidence of coronary artery disease at 1 year, were compared with a cohort of 25 patients (control group) who underwent transplantation primarily in 2000 and in early 2002 treated with cyclosporine, mycophenolate mofetil, and glucocorticoids. All patients were followed up for at least 12 months. RESULTS: Kaplan-Meier actuarial 1-year survival rates were equivalent between groups (97% for the treatment group and 88% for the control group), as was freedom from allograft rejection (48% and 42% for treatment and control groups, respectively). No cases of transplant arteriopathy were noted within the first posttransplantation year. Renal function was not significantly affected in either group. There was a striking increased incidence of mediastinitis in the treatment group (19%) versus 0% in the control group (P = .02). Tacrolimus-sirolimus therapy was associated with a nearly 11-fold increased incidence of new-onset diabetes mellitus as well (P = .004). CONCLUSION: Tacrolimus, sirolimus, and steroids (following low-dose rabbit antithymocyte globulin) were associated with an increased incidence of mediastinitis and posttransplantation diabetes mellitus. No obvious long-term benefit on survival, arteriopathy, or renal function was noted.

Low- vs high-dose aspirin. Effects on platelet function in hyperlipoproteinemic and normal subjects.

Low-dose aspirin may be inadequate for inhibition of platelet function in hyperlipoproteinemics due to increased platelet reactivity. Platelet function was studied in 18 type II hyperlipoproteinemic and 12 normal subjects after at least ten days of treatment with placebo and with low-dose (0.45 mg/kg/day) and high-dose (900 mg/day) aspirin. In the normal and hyperlipoproteinemic subjects, low-dose aspirin produced near maximal (90%) inhibition of platelet thromboxane generation, significant prolongation of the bleeding time, and significant inhibition of platelet aggregation, similar in degree to the inhibition produced by high-dose aspirin. There was no significant difference between hyperlipoproteinemic and normal subjects in any of the platelet function measures before and after aspirin treatment. Thus, a daily 0.45-mg/kg aspirin dose (20 to 45 mg) effectively inhibited platelet function in type II hyperlipoproteinemics, who do not appear to have an increased dose requirement for aspirin.

Omega-3 fatty acids in hypertriglyceridemic patients: triglycerides vs methyl esters.

The purpose of this study was to compare the relative effects of omega-3 fatty acids (omega-3 FAs) in the triglyceride (TG) and methly ester (ME) forms in a crossover design in patients with type IV hyperlipidemia. Eight male patients were given 18 vegetable-oil capsules (control); 18 capsules of a TG rich in omega-3 FAs (omega-3 TG); and 11 capsules containing omega-3-FA MEs (omega-3 ME). One supplement was given during each of three 6-wk periods. Equivalent amounts of omega-3 FAs (6.8 g/d) were provided by each of the omega-3 treatments. Plasma cholesterol (C) levels were unchanged during the two omega-3 phases whereas plasma TG levels fell by 44% during both. Low-density-lipoprotein cholesterol (LDL-C) levels rose significantly with both omega-3-FA treatments, as did apolipoprotein B levels. When taken in either the TG or ME forms, omega-3 FAs are equally effective hypotriglyceridemic agents but they may raise LDL-C levels.

Synergy, activity and tolerability of zidovudine and interferon-alpha in patients with symptomatic HIV-1 infection: AIDS Clincal Trial Group 068.

Thirty-four subjects with symptomatic HIV-1 infection, p24 antigenaemia, and CD4 cell counts > 200/mm3 were randomly assigned to receive treatment with either zidovudine (ZDV) orally, interferon-alpha (IFN-alpha) subcutaneously, or both at respective low (200 mg ZDV/ 2 million international units IFN-alpha (MIU)), middle (400 mg/4 MIU) or high (600 mg/6 MIU) daily dose levels for 12 weeks. Thereafter, all patients received combination therapy at the initially assigned dose level to a total of 96 weeks. This design permitted analysis by the combination index (CI) method, which demonstrated antiretroviral synergy between ZDV and IFN-alpha with respect to p24 antigen suppression. Over the first 12 weeks, combination therapy was acceptably tolerated, more so than IFN-alpha monotherapy, and it was significantly more active in suppressing antigenaemia than either of the monotherapies. Similarly, the high-dose combination was the most active dose level over weeks 12 to 96. Combination ZDV/IFN-alpha at the optimal dose level defined by this trial merits further study. In addition, the CI design strategy employed here may be useful for the investigation of new antiretroviral combinations.

Effects of dietary fish oil on platelet function and plasma lipids in hyperlipoproteinemic and normal subjects.

We studied the effects of dietary supplementation with an encapsulated fish oil concentrate (Maxepa) on platelet function, fibrinolysis, and plasma lipids and lipoproteins in 9 normal subjects, 10 patients with type IV hyperlipoproteinemia, and 6 with type IIB hyperlipoproteinemia. After a baseline period, the subjects crossed over randomly between treatment periods with Maxepa (providing 3.24 g eicosapentaenoic acid and 2.16 g docosahexaenoic acid per day) and safflower oil (used as a control), given for 6 weeks each. Administration of Maxepa led to a slight prolongation of the bleeding time in all groups and to modest inhibition of platelet aggregation in the type IV hyperlipoproteinemics and normal subjects, with partial (41%) inhibition of thromboxane synthesis from baseline levels noted in the normal group. Plasma total fibrinolytic actively did not change significantly in any group. Maxepa treatment resulted in a marked decrease in triglyceride and VLDL-cholesterol and a slight increase in HDL-cholesterol was noted after Maxepa in the type IV hyperlipoproteinemics (4.11 +/- 0.13 mmol/l vs. 3.10 +/- 0.16 mmol/l, Maxepa vs. safflower oil). We conclude that dietary supplementation with fish oil results in a relatively minor degree of inhibition of platelet function in normal and hyperlipoproteinemic subjects, and a potentially adverse increase in LDL-cholesterol in type IV hyperlipoproteinemics.

The effect of 5'-amino-5'-deoxythymidine on the pattern of polyadenylation of herpes simplex virus type 1 ribonucleic acid.

Treatment of herpes simplex virus type 1 (HSV-1) infected Vero cells with 5'-amino-5'-deoxythymidine (AdThd) causes a 65% reduction in the amount of total viral RNA present at late times of infection. This decrease is apparent as early as 6 hours post infection, affecting the levels of viral cytoplasmic polyadenylated (poly(A+] species to a greater extent than non-polyadenylated (poly(A-] RNA. Cytoplasmic viral poly(A+) RNA is present in AdThd-treated cultures at only 10% control poly(A+) levels, yet there is no evidence of a direct inhibition of RNA polyadenylation. Underrepresentation of RNA species in the cytoplasm is not sequence-specific. The results suggest that the antiviral activity of AdThd may involve not only incorporation into viral DNA, with a resultant decrease in viral transcription, but also perturbation of the relative amounts of viral poly(A+) RNA and poly(A-) RNA.