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Biomedical subjects

S Wolf

Publications and source records attributed to S Wolf.

At least 73 records · Page 4Linked to original sources

The brown algal virus EsV-1 particle contains a putative hybrid histidine kinase.

The Ectocarpus siliculosus virus, EsV-1, occurs worldwide in all populations of the filamentous marine brown alga E. siliculosus. We have screened an expression library of EsV-1 restriction fragments and identified a DNA clone with the potential to code for a 52-kDa histidine protein kinase. The derived amino acid sequence includes all homology boxes diagnostic for histidine protein kinases and, in addition, amino acid motifs that are commonly found in response regulators of bacterial two-component signal transduction proteins. Thus, the novel viral protein can be classified as a hybrid histidine protein kinase of a type that has previously been detected in fungi, slime molds, and plants. By using purified antibodies, we found that the protein with its potential kinase activity is located on the outer shell of viral particles. This is the first report on a two-component regulator-like protein in viruses and could provide the basis for speculations with regard to the evolution of EsV-1 and related viruses.

Amino Acid Sequence↗

3D raman sideband cooling of cesium atoms at high density

We laser cool 5x10(7) Cs atoms to a spin-polarized phase space density of 1/30, the highest ever obtained by laser cooling. It is achieved by compression and polarization gradient cooling in a 3D far-off-resonant optical lattice, followed by 3D Raman sideband cooling optimized at a density of 1.5x10(12) atoms/cm(3), and adiabatic release. In the lattice, 23% of the sites are occupied, 95% of the atoms are in the lowest energy magnetic sublevel, and 37% are in the lowest 3D vibrational state.

Journal Article↗

Characterization and immunolocalization of major structural proteins in the brown algal virus EsV-1.

The Ectocarpus siliculosus virus (EsV-1) is endemic in all populations of the cosmopolitan filamentous brown alga Ectocarpus siliculosus. EsV-1 has a large circular double-stranded DNA genome of about 320 kilobase pairs, and a complex virion structure with a central nucleoprotein core surrounded by several proteinaceous layers. To investigate the protein composition of the virion, we screened an expression library of EsV-1 with antibodies raised against purified detergent-disrupted viral particles. We isolated several clones encoding novel structural proteins and investigated two of them in detail. These clones encode viral proteins vp55 and vp74. Electron microscopy reveals that vp55 is most likely a component of the surface of the viral core, whereas vp74 may be part of an inner core structure. To initiate a genetic analysis, we sequenced regions of the EsV-1 genome encoding vp55 and vp74 and found several adjacent open reading frames with the potential to code for several interesting viral proteins including a putative calcium-binding protein, a collagen-like protein, and a RING finger protein.

Amino Acid Sequence↗

Ability of systemic interleukin-12 to hamper progressive stages of mammary carcinogenesis in HER2/neu transgenic mice.

Previous studies in mice have shown that chronic administration of recombinant interleukin-12 (IL-12) hampers the progression of both chemical- and oncogene-dependent carcinogenesis. This suggests that a new preventive strategy may be envisaged for individuals with a genetic risk of cancer or carrying preneoplastic lesions. Starting at progressive stages of mammary carcinogenesis, female BALB/c and FVB mice carrying the activated rat HER2/neu oncogene (BALB-neuT) or the proto-oncogene (FVB-neuN) under the mouse mammary tumor virus promoter received multiple 5-day courses of different doses of IL-12. The times of tumor appearance, multiplicity, and histopathological features of the neoplastic lesions were evaluated. In both BALB-neuT and FVB-neuN mice, 5-day i.p. courses of 50/100 ng of IL-12/day inhibited mammary carcinogenesis when they coincided with the progression of early preneoplastic lesions. Inhibition appears to depend primarily on the ability of IL-12 to interfere with early tumor angiogenesis. Later treatments are much less effective, and daily doses of 10 and 2 ng are useless. The efficacy of early IL-12 courses suggests that they could be used to prevent mammary tumors in individuals at risk, whereas their lower efficacy in later stages of carcinogenesis and the dose range required pose some constraints on their use in the management of overt preneoplastic lesions. Precise understanding of tumor progression means that effective treatments can be commenced relatively late in the life of individuals at risk and that no lifetime administration is required.

Animals↗

[Mechanical modification of callus healing].

Interfragmentary movement and size of the fracture gap influence fracture healing. Limited movements promote callus formation and may result in increased mechanical stability. Although larger movements still promote callus formation, the bony consolidation of the fracture is hampered. Fracture healing is also hampered if the size of the fracture gap is too large. A combination of large movement and large gap bears the risk of non-union. Therefore, having in mind a minimally invasive surgical approach, one should strive for good reduction of the fracture ends and flexible yet stable osteosynthesis. Dynamization of the fracture by enabling axial movement will close the fracture gap, stimulate tissue differentiation and possibly accelerate the healing process. External mechanical stimulation, however, has not been shown to effectively enhance the healing process under flexible fixation or in load-bearing patients.

Animals↗

Inhaled endothelin A antagonist improves arterial oxygenation in experimental acute lung injury.

OBJECTIVES: To study the effects of an inhaled endothelin A (ET(A)) receptor antagonist on hemodynamics and pulmonary gas exchange in experimental acute lung injury (ALI). DESIGN AND SETTING: Prospective, randomized, and controlled study in a university laboratory. PARTICIPANTS AND INTERVENTIONS: Sixteen pigs were ventilated in a volume controlled mode during general anesthesia. ALI was induced by surfactant depletion using repetitive lung lavages until the PaO2/FIO2 ratio was below 100 mmHg. The animals were then randomly assigned to receive either a nebulized ET(A) receptor antagonist (LU-135252, 3 mg/kg, inhaled over 1 h; LU group) or nebulization of saline (5-10 ml inhaled over 1 h) with no further intervention (controls). MEASUREMENTS AND RESULTS: Parameters of hemodynamics and gas exchange were measured for 6 h after induction of ALI. In the LU group intrapulmonary right-left shunting (QS/QT) decreased from 58 +/- 8% at the onset of ALI to 27 +/- 12% 3 h and 24 +/- 9% 6 h after ALI (p < 0.05); PaO2 increased from 55 +/- 12 to 257 +/- 148 mmHg 3 h and 270 +/- 136 mmHg 6 h after ALI. (p < 0.05), whereas in controls QS/QT and PaO2 did not improve over the 6 h after onset of ALI. In the LU group mean pulmonary artery pressure was stable for 6 h after ALI (26-29 mmHg), while in controls it increased from 28 +/- 2 to 41 +/- 2 mmHg (p < 0.05). Inhaled LU-135252 reduced cardiac output by 31 +/- 11% (p < 0.05) and increased systemic vascular resistance by 60 +/- 29 % (p < 0.05), while these parameters remained stable in controls. CONCLUSION: In this porcine model of ALI the inhalation of an ET(A) receptor antagonist improved arterial oxygenation and maintained a stable pulmonary artery pressure without inducing systemic vasodilatation.

Administration, Inhalation↗

Vertebral body replacement with a bioglass-polyurethane composite in spine metastases--clinical, radiological and biomechanical results.

Metastatic spine lesions frequently require corpectomy in order to achieve decompression of the spinal cord and restoration of spinal stability. A variety of systems have been developed for vertebral body replacement. In patients with prolonged life expectancy due to an improvement of both systemic and local therapy, treatment results can be impaired by a loosening at the implant-bone interface or mechanical failure. Furthermore, early detection of a metastatic recurrence using sensitive imaging modalities like computed tomography (CT) and magnetic resonance imaging (MRI) is possible in these patients without artefact interference. The aim of our pilot study was to evaluate the clinical applicability and results of a new radiolucent system for vertebral body replacement in the lumbar spine. The system consists of bone-integrating biocompatible materials - a polyetherurethane/bioglass composite (PU-C) replacement body and an integrated plate of carbon-fibre reinforced polyetheretherketone (CF-PEEK) - and provides high primary stability with anterior instrumentation alone. In a current prospective study, five patients with metastatic lesions of the lumbar spine were treated by corpectomy and reconstruction using this new system. Good primary stability was achieved in all cases. Follow-up (median 15 months) using CT and MRI revealed progressive osseous integration of the PU-C spacer in four patients surviving more than 6 months. Results obtained from imaging methods were confirmed following autopsy by biomechanical investigation of an explanted device. From these data, it can be concluded that implantation of the new radiolucent system provides sufficient long-term stability for the requirements of selected tumour patients with improved prognosis.

Adult↗

A case control study of multiple myeloma at four nuclear facilities.

PURPOSE: Reported elevations of multiple myeloma among nuclear workers exposed to external penetrating ionizing radiation, based on small numbers of cases, prompted this multi-facility study of workers at US Department of Energy facilities. METHODS: Ninety-eight multiple myeloma deaths and 391 age-matched controls were selected from the combined roster of 115,143 workers hired before 1979 at Hanford, Los Alamos National Laboratory, Oak Ridge National Laboratory, and the Savannah River site. These workers were followed for vital status through 1990 (1986 for Hanford). Demographic, work history, and occupational exposure data were derived from personnel, occupational medicine, industrial hygiene, and health physics records. Exposure-disease associations were evaluated using conditional logistic regression. RESULTS: Cases were disproportionately African American, male, and hired prior to 1948. Lifetime cumulative whole body ionizing radiation dose was not associated with multiple myeloma, however, there was a significant effect of age at exposure, with positive associations between multiple myeloma and doses received at older ages. Dose response associations increased in magnitude with exposure age (from 40 to 50) and lag assumption (from 5 to 15 years), while a likelihood ratio goodness of fit test reached the highest value for cumulative doses received at ages above 45 with a 5-year lag (X2=5.43,1 df; relative risk = 6.9% per 10 mSv). Dose response associations persisted with adjustment for potential confounders. CONCLUSIONS: Multiple myeloma was associated with low level whole body penetrating ionizing radiation doses at older ages. The exposure age effect is at odds with interpretations of A-bomb survivor studies but in agreement with several studies of cancer among nuclear workers.

Age Factors↗

Heterogeneity of the API2-MALT1 gene rearrangement in MALT-type lymphoma.

The translocation t(11;18)(q21;q21), which is the most frequent chromosomal aberration in extranodal marginal zone B cell lymphomas of MALT-type, was characterised in a series of 34 biopsies, including 18 gastric non-Hodgkin's lymphomas (NHL) of MALT-type, six MALT-type NHL of extragastral origin and 10 extranodal large B cell lymphomas (LBL). Based on fluorescence in situ hybridisation, STS-PCR analysis and screening of genomic PAC libraries, a physical map of contiguous DNA probes on chromosome 11 was constructed containing the anti-apoptotic genes API2 and API1 adjacent to the translocation breakpoint. RACE-PCR experiments revealed MALT1 the chromosome 18-derived fusion partner of API2, which has also been reported recently by other groups. RT-PCR analysis and DNA sequencing demonstrated the expression of an API2-MALT1 fusion transcript in 18/24 gastral and extragastral MALT-type lymphomas. In none of 10 LBLs was a translocation specific RT-PCR product detected. Five variants of the fusion transcript were identified and in all instances the open reading frame of the fused portion of the MALT1 gene was maintained. The molecular analysis of these variants allowed the design of optimised assays for the diagnosis of the API2-MALT1 gene rearrangement.

Caspases↗

Cytokines and soluble cytokine receptor induction after IL-12 administration in cancer patients.

This study shows that subcutaneous administration of increasing doses of IL-12, once a week, in 21 cancer patients increased the expression of cytokine genes (interferon-gamma (IFN-gamma), tumour necrosis factor-alpha (TNF-alpha), IP-10, MIG, IL-10, IL-4) in peripheral blood mononuclear cells even at very low doses (30 ng/kg). Surprisingly, no circulating TNF-alpha or IL-4 could be detected in the plasma of patients treated with IL-12. However, a marked increase of soluble IL-4 receptor was demonstrated in the plasma of five of the six patients studied, which may represent an additional mechanism by which IL-12 inhibits the development of the Th2 response in vivo. A marked decline of IFN-gamma and IP10 induction was recorded after repeated cycles of IL-12. In contrast, in most patients IL-12 increased IL-10 expression with no subsequent decrease during the course of therapy, and even an earlier peak of IL-10 induction at the 6th cycle. In addition, a constant up-regulation of serum soluble IFN-gamma receptor levels was observed after each cycle of IL-12 treatment with a delayed peak compared with the IFN-gamma peak. The constant rise of IL-10 and soluble IFN-gamma receptor during IL-12 therapy may therefore contribute to the inhibition of IFN-gamma activity detected after repeated cycles of IL-12. Lastly, a marked heterogeneity of cytokine induction was observed from one patient to another, which appeared to be independent of the dose of IL-12 administered. These data may lead to a better understanding of the biological activity of IL-12 and the in vivo mechanisms of its regulation.

Antineoplastic Agents↗

Nonunion of the mandible: an analysis of contributing factors.

PURPOSE: The aim of this study was to review our experience of nonunion of mandible fractures and to compare this information with the past and present literature. The analysis also evaluated risk factors and those conditions that lead to nonunion so that the complication may be better managed and possible avoided. PATIENTS AND METHODS: A retrospective review of mandible fractures in a major medical center was carried out on patients treated from 1994 through 1998. The nonunion cases were evaluated for factors such as age, sex, race, cause of fracture, location of fracture, delay until the patient obtained treatment, teeth in the fracture line, use of antibiotics, multiplicity of fractures, degree of fragmentation, medical problems, and drug and alcohol abuse. The adequacy of reduction and appropriateness of the fixation techniques were evaluated by analysis of the postoperative imaging studies. Postoperative occlusion and patient compliance were also included in the evaluation. RESULTS: Of the 906 patients with 1,432 mandible fractures, there were 25 nonunion complications, for an incidence of 2.8%. Most patients with nonunion were men who had received the fracture as a result of an altercation. The nonunion was frequently noted in the body, and was almost twice as common (39% vs 17.6%) in patients with multiple fractures than in a randomly selected group who did not have the complication. Delayed treatment was noted in 8 of the patients, and teeth were present in the fracture line in another 8. Alcohol and drug abuse were prevalent, and 1 of 5 of the patients removed their fixation devices. Eight patients were believed to be stabilized inadequately, and 1 patient also had a poor reduction. Osteomyelitis was a common complication. CONCLUSIONS: The incidence of nonunion appears to be unchanged over time regardless of the varied and presumably advanced methods of fixation and reduction. Multiple fractures were a contributory factor, and the body of the mandible appeared to be a common site. Many patients had osteomyelitis associated with the nonunion. Inadequate stabilization or reduction were important causes. Other suspected contributory factors included failure to provide antibiotics, delay in treatment, teeth in the fracture line, alcohol and drug abuse, inexperience of the surgeon, and lack of patient compliance.

Adult↗

Triage of patients for a rapid (5-minute) electrocardiogram: A rule based on presenting chief complaints.

STUDY OBJECTIVE: A rule based on presenting chief complaints can identify patients for a rapid (5-minute) ECG and decrease delays in treatment of patients with acute myocardial infarction (MI). METHODS: The presenting chief complaint was electronically collected on all patients treated in a community teaching hospital emergency department. A rule for ordering ECG on patient presentation to the ED was developed from a model set of patients presenting from July through December 1994 (22,717 patients) and then tested on a validation set of patients from January through May 1995 (18,759 patients). Outcome measures (delay in performance of ECG and delay in administration of thrombolytic agents) were prospectively collected on written data sheets before (April 1993-May 1995, n=67) and after (June 1995-March 1997, n=128) implementation of the rule at the study hospital. RESULTS: On the model set, 193 patients had the final diagnosis of MI, with 5 chief complaints having the best performance in identifying patients with acute MI and comprising the rapid ECG rule: older than 30 years with chest pain (130 [67.4%] patients); older than 50 years with syncope (5 [1%] patients); weakness (12 [6.2%] patients); rapid heart beat (2 [1%] patients); and difficulty breathing or shortness of breath (20 [10.4%] patients). On the validation set, 142 patients had the final diagnosis of MI, with the rule performing better than chest pain in identifying patients for a "stat" ECG (sensitivity 93.7% versus 67. 4% [95% confidence interval (CI) of the difference, 15.6% to 33.8%]), although a larger percentage of ED patients would receive a stat ECG (7.3% versus 6.3% [95% CI of the difference, 0.7% to 1.7%]). During the model and validation period, 44 (13.1%) of 335 patients with MI received thrombolytic agents. The rule had higher sensitivity on patients with MI treated with thrombolytic agents compared with patients with MI not treated with thrombolytic agents (sensitivity 100% versus 86.4% [95% CI of the difference, 1.7% to 20. 3%] and specificity of 90.4% versus 93.8% [95% CI of the difference, 3.0% to 3.8%]). For the 4-year study period, outcome improved after the implementation of the rule: mean delay in performing ECGs in patients with MI who were administered thrombolytic agents decreased from 10.0 to 6.3 minutes (95% CI of the difference, 1.1 to 6.4), and mean delay in administering thrombolytic agents decreased from 36.9 to 26.1 minutes (95% CI of the difference, 3.5 to 17.7). CONCLUSION: Use of a rule based on chief complaints can identify patients with MI for immediate ECG and decrease delays in performing ECGs and administration of thrombolytic agents.

Adult↗

Cucumber mosaic virus infection affects sugar transport in melon plants.

Viral infection often affects carbon assimilation and metabolism in host plants. To better understand the effect of cucumber mosaic virus (CMV) infection on sugar transport, carbohydrate levels and the amounts of the various sugars in the phloem sap were determined in infected melon (Cucumis melo L.) plants. Source leaves infected with CMV were characterized by high concentrations of reducing sugars and relatively low starch levels. The altered level of carbohydrates was accompanied by increased respiration and decreased net photosynthetic rates in the infected leaves. Although stachyose was the predominant sugar in phloem sap collected from petioles of control leaves, sucrose (Suc) was a major sugar in the phloem sap of infected leaves. Moreover, analyses of the newly fixed (14)CO(2) revealed a high proportion of radioactive Suc in the phloem sap of infected leaves 60 min post-labeling. The alteration in phloem sap sugar composition was found in source, but not old, leaves. Moreover, elevations in Suc concentration were also evident in source leaves that did not exhibit symptoms or contain detectable amounts of virus particles. The mode by which CMV infection may cause alterations in sugar transport is discussed in terms of the mechanism by which sugars are loaded into the phloem of cucurbit plants.

Base Sequence↗

Modeling mode arrivals in the 1995 SWARM experiment acoustic transmissions

As part of the Shallow Water Acoustics in a Random Medium (SWARM) experiment, a 16 element WHOI vertical line array (WVLA) was moored in 70 m of water off the New Jersey coast. A 400-Hz acoustic tomography source was moored some 32-km shoreward of this array, such that an acoustic path was created that was anti-parallel to the primary propagation direction for shelf-generated internal wave solitons. The presence of these soliton internal waves in the acoustic waveguide causes significant coupling of energy between propagating acoustic modes, creating fluctuations in modal intensities and modal peak arrival times, as well as time spreading of the pulses. Two methods by which acoustic propagation and scattering in soliton-filled waveguides can be modeled are presented here in order to understand and explain the scattering observed in the SWARM field data. The first method utilizes the Preisig and Duda [IEEE J. Ocean. Eng. 22, 256-269 (1997)] Sudden Interface Approximation (SIA) to represent the solitons. The second method, which is computationally slower, uses a finely meshed, "propagated" thermistor record to simulate the solitons in the SWARM experiment waveguide. Both numerical methods are found to generate scattering characteristics that are similar to the SWARM field data.

Journal Article↗

Acoustic normal mode fluctuation statistics in the 1995 SWARM internal wave scattering experiment

In order to understand the fluctuations imposed upon low frequency (50 to 500 Hz) acoustic signals due to coastal internal waves, a large multilaboratory, multidisciplinary experiment was performed in the Mid-Atlantic Bight in the summer of 1995. This experiment featured the most complete set of environmental measurements (especially physical oceanography and geology) made to date in support of a coastal acoustics study. This support enabled the correlation of acoustic fluctuations to clearly observed ocean processes, especially those associated with the internal wave field. More specifically, a 16 element WHOI vertical line array (WVLA) was moored in 70 m of water off the New Jersey coast. Tomography sources of 224 Hz and 400 Hz were moored 32 km directly shoreward of this array, such that an acoustic path was constructed that was anti-parallel to the primary, onshore propagation direction for shelf generated internal wave solitons. These nonlinear internal waves, produced in packets as the tide shifts from ebb to flood, produce strong semidiurnal effects on the acoustic signals at our measurement location. Specifically, the internal waves in the acoustic waveguide cause significant coupling of energy between the propagating acoustic modes, resulting in broadband fluctuations in modal intensity, travel-time, and temporal coherence. The strong correlations between the environmental parameters and the internal wave field include an interesting sensitivity of the spread of an acoustic pulse to solitons near the receiver.

Journal Article↗