Search PubMed⌕ Search

Biomedical subjects

J Goldman

Publications and source records attributed to J Goldman.

At least 37 records · Page 2Linked to original sources

Extraction of R = sigma(L)/sigma(T) from CCFR nu(mu)-Fe and nu(mu)-Fe differential cross sections.

We report on the extraction of R = sigma(L)/sigma(T) from CCFR nu(mu)-Fe and nu(mu)-Fe differential cross sections. The CCFR differential cross sections do not show the deviations from the QCD expectations that are seen in the CDHSW data at very low and very high x. R as measured in nu(mu) scattering is in agreement with R as measured in muon and electron scattering. All data on R for Q(2)>1 GeV(2) are in agreement with a NNLO QCD calculation which uses NNLO parton distribution functions and includes target mass effects. We report on the first measurements of R in the low x and Q(2)<1 GeV(2) region (where an anomalous large rise in R for nuclear targets has been observed by the HERMES Collaboration).

Journal Article↗

Search for the lepton family number violating process nu(mu)e(-) --> mu(-)nu(e).

The NuTeV experiment at Fermilab has used a sign-selected neutrino beam to perform a search for the lepton number violating process nu(mu)e(-)-->mu(-)nu(e), and to measure the cross section of the standard model inverse muon decay process nu(mu)e(-)-->mu(-)nu(e). NuTeV measures the inverse muon decay asymptotic cross-section slope sigma/E to be (13.8 +/- 1.2 +/- 1.4) x 10(-42) cm(2)/GeV. The experiment also observes no evidence for lepton number violation and places one of the most restrictive limits on the cross-section ratio sigma(nu(mu)e(-)-->mu(-)nu(e))/sigma(nu(mu)e(-)-->mu(-)nu(e)) < or = 1.7% at 90% C.L. for V-A couplings and < or = 0.6% for scalar couplings.

Journal Article↗

Observation of an anomalous number of dimuon events in a high energy neutrino beam.

A search for long-lived neutral particles ( N0's) with masses above 2.2 GeV/c(2) that decay into at least one muon has been performed using an instrumented decay channel at the NuTeV experiment at Fermilab. Data were examined for particles decaying into the final states mumu, mu(e), and mu(pi). Three mumu events were observed over an expected standard model background of 0.069+/-0.010 events; no events were observed in the other modes.

Journal Article↗

First measurement of the low- x, low- Q(2) structure function F(2) in neutrino scattering.

A new structure function analysis of CCFR deep inelastic nu-N and nu-N scattering data is presented for previously unexplored kinematic regions down to Bjorken x = 0.0045 and Q(2) = 0.3 GeV(2). Comparisons to charged lepton scattering data from NMC and E665 experiments are made and the behavior of the structure function F(2)(nu)2 is studied in the limit Q(2)-->0.

Journal Article↗

Measurements of F2 and xF(nu)(3) - xF(nu;)(3) from CCFR nu(mu)-Fe and nu;(mu)-Fe Data in a Physics Model-Independent Way.

We report on the extraction of the structure functions F2 and DeltaxF(3) = xF(nu)(3)-xF(nu;)(3) from CCFR nu(mu)-Fe and nu;(mu)-Fe differential cross sections. The extraction is performed in a physics model-independent (PMI) way. This first measurement of DeltaxF(3), which is useful in testing models of heavy charm production, is higher than current theoretical predictions. The ratio of the F2 (PMI) values measured in nu(mu) and mu scattering is in agreement (within 5%) with the predictions of next-to-leading-order parton distribution functions using massive charm production schemes, thus resolving the long-standing discrepancy between the two sets of data.

Journal Article↗

Direct visualization of cytomegalovirus-specific T-cell reconstitution after allogeneic stem cell transplantation.

Cytomegalovirus (CMV) remains an important cause of morbidity and mortality after allogeneic stem cell transplantation (SCT), but cytotoxic T lymphocytes (CTL) may play a critical role in controlling CMV reactivation. Fluorescent HLA-peptide tetramers containing immunodominant peptides from CMV were used to prospectively monitor the recovery of CMV CTL in recipients of allogeneic transplants from siblings (n = 13) or unrelated donors (n = 11). In patients given allografts from a sibling when both the patient and donor were seropositive for CMV before SCT, recovery of CMV-specific CTL was rapid and reached up to 21% of all CD8(+) T cells. Early reconstitution of CMV-specific immunity was not observed if either the donor or recipient was seronegative for CMV. In recipients of transplants from volunteer unrelated donors, recovery of CMV-specific CTL was delayed in comparison to that in recipients of transplants from siblings and no CTL were observed within the first 100 days after SCT. CTL numbers were increased after episodes of CMV reactivation but were suppressed by prednisolone therapy. Recovery of CMV-specific CTL to levels greater than 10 x 10(6)/L was associated with protection from CMV disease. It was concluded that use of HLA-peptide tetramers to quantify CMV CTL is valuable for studying T-cell responses after allogeneic SCT. It should allow prediction of CMV reactivation in individual patients and assist in the development of adoptive T-cell immunotherapy.

Adolescent↗

Parainfluenza virus 3 infection after stem cell transplant: relevance to outcome of rapid diagnosis and ribavirin treatment.

All 456 recipients of hemopoietic stem cell transplants (SCT) at the Hammersmith Hospital, London, from January 1990 through September 1996 were reviewed for parainfluenza virus (PIV) infections. Of the 24 (5.3%) PIV type 3 (PIV3)-infected patients, 10 had upper respiratory tract infection and all survived, but 8 of 14 with pneumonia died. A same-day immunofluorescence test diagnosed PIV3 infection in 20 (83%) of the 24 cases, but virus culture diagnosed only 10 (42%) of the 24 cases after a mean delay of 12 days. Eighteen PIV3-infected patients first received ribavirin at a median of 3 days after onset of symptoms, but, nevertheless, 2 patients shed PIV3 for 4 months. Six of 10 patients with pneumonia died despite early ribavirin therapy. The cause of death was not established by autopsy; 3 patients had concurrent infections, but in 3, only PIV3 was detected. The value of immunofluorescence testing for early diagnosis and treatment of PIV3 infection after SCT is demonstrated, but the outcome was not altered.

Adolescent↗

An investigation of clinical correlates of Lewy bodies in autopsy-proven Alzheimer disease.

BACKGROUND: Studies of patients meeting clinical and pathologic criteria for Alzheimer disease (AD) have not consistently found associations between the presence of Lewy bodies (LBs) at postmortem examination and a higher frequency during life of the clinical features of dementia with LBs. OBJECTIVE: To evaluate the clinical correlates of LBs in patients with AD. DESIGN AND METHODS: Fifty-one patients were diagnosed as having probable AD during life and met pathologic criteria for AD. Semiquantitative ratings for LBs were obtained in 4 brain regions: substantia nigra, cingulate, insular cortex, and hippocampus. The patients had been followed up semiannually for up to 9.9 years before death, and clinical features associated with dementia with LBs, including extrapyramidal signs and visual hallucinations, were assessed at each study visit. Logistic regression analyses determined whether patients who had LBs were more likely than those without LBs to express specific clinical signs during follow-up. Cox analyses determined whether patients with LBs developed clinical signs or died earlier. Generalized estimating equations were used to compare rates of cognitive or functional change. RESULTS: Nineteen of the 51 patients had at least 1 LB in one of the studied regions. In no case was a significant relation noted between LBs and the presence of a measured clinical sign. No LB measure was associated with an increased risk of developing any of the evaluated clinical signs earlier in the disease. There was no association between the presence of LBs and more rapid mortality or more rapid disease progression. CONCLUSIONS: In patients diagnosed as having AD during life, we did not observe a relation of LBs noted during postmortem examination with the presence of any clinical feature that we assessed or with the rapidity of disease progression. The relation between LBs and specific clinical manifestations may be tenuous in these patients.

Aged↗

Role of tensile stress and strain in the induction of cell death in experimental vein grafts.

Tensile stress and strain are known to induce vascular cell proliferation, a process that is physiologically counterbalanced by cell death. Here we investigate whether tensile stress and strain regulate vascular-cell death by using an end-to-end anastomosed rat vein graft model. In such a model, the circumferential tensile stress in the graft wall was increased by approximately 140 times immediately after surgery compared with that in the venous wall. This change was associated with an increase in the percentage of TUNEL-positive cells at 1, 6, 24, 120, 240, and 720h with two distinct peaks at 1 and 24h (10.1+/-3.5 and 14.4+/-3.2%, respectively) compared with that in control jugular veins (0.4+/-0.5 and 0.5+/-0.5% at 1 and 24h, respectively). When tensile stress and strain in the vein graft wall were reduced by using a biomechanical engineering approach, the rate of cell death was reduced significantly (3.6+/-1.1 and 1.6+/-0.5% at 1 and 24h, respectively). Furthermore, DEVD-CHO, a tetrapeptide aldehyde that inhibits the activity of caspase 3, significantly suppressed this event. These results suggest that a step increase in tensile stress and strain in experimental vein grafts induces rapid cell death, which is possibly mediated by cell death signaling mechanisms.

Anastomosis, Surgical↗

Implications of imatinib mesylate for hematopoietic stem cell transplantation.

The ability of allogeneic bone marrow or blood stem cell transplantation (SCT) to induce long-term remission or cure of chronic myeloid leukemia (CML) is well established. However, the use of this treatment is limited by the availability of suitable human leukocyte antigen (HLA) identical siblings or matched unrelated donors (MUD). As a consequence only a relatively small proportion of CML patients are eligible for a transplant, and of these not all are cured. The preliminary results of trials using the new Bcr-Abl kinase inhibitor imatinib mesylate (formerly CGP57-148B, STI571, Gleevec) to treat CML are very encouraging. However, a number of important questions cannot yet be answered: Can imatinib mesylate induce durable molecular remissions? Can the drug prolong survival in comparison with other nontransplant treatments? and, can it actually cure CML patients? Until answers to these questions are available, SCT and use of interferon-alfa (IFN-alpha) alone or in combination (perhaps with imatinib mesylate) must remain major therapeutic options. I summarize here the advantages and disadvantages associated with currently available therapy. I review three different approaches to initial treatment of the CML patient diagnosed in chronic phase, and make a tentative recommendation for one of these options. It is likely that the situation will alter considerably in the foreseeable future.

Algorithms↗

Stem cell transplantation for chronic myeloid leukaemia: the role of infused marrow cell dose.

INTRODUCTION: Allogeneic stem cell transplantation is a potentially curative option for patients with CML. The optimal donor is an HLA-identical sibling but transplants using unrelated volunteers can also be successful. The factors influencing survival after allogeneic SCT for CML are reasonably well defined. Recently however, the Seattle group have emphasised the influence of a high marrow cell dose on outcome following volunteer unrelated donor SCT for high risk acute leukaemia. MATERIALS AND METHODS: We have sought to define factors impacting on transplant related mortality (TRM) in a population of CML patients after allografting with matched sibling or alternative stem cell donors at a single centre over a 20-year period, with emphasis on infused marrow cell dose. Factors entered into a multivariate analysis were: recipient age, recipient CMV serostatus, disease phase, donor sex, cell dose and frequency of CTLP reactivity. RESULTS: In multivariate analysis four factors had an adverse effect on TRM when using a VUD: low marrow cell dose (<3.65 x 10(8) TNC/kg, relative risk 2.05, CI 1.08-3.90, P = 0.029), late disease phase (relative risk 1.68, CI 1.03-2.74, P = 0.038), patient CMV seropositivity (relative risk 1.98, CI 1.25-3.13, P = 0.004) and high frequency of CTLP (relative risk 1.93, CI 1.18-3.13, P = 0.008). For HLA-identical sibling donor transplants the only factor that adversely impacted on TRM was late disease phase (P = 0.0004 in univariate analysis). CONCLUSION: High infused cell dose is a new modifiable factor associated with reduced TRM following allogeneic SCT using an unrelated donor for the treatment of CML. The data support the recommendation that bone marrow harvest teams should aim to collect the highest possible number of nucleated cells for recipients of unrelated donor transplants.

Adult↗

Role of blood shear stress in the regulation of vascular smooth muscle cell migration.

Smooth muscle cell (SMC) migration from the media to the intima of blood vessels contributes to neointimal formation and atherogenesis. Here, we demonstrate how blood shear stress regulates vascular SMC migration in the encapsulating tissue of a micro-cylinder implanted in the center of the rat vena cava with the micro-cylinder perpendicular to blood flow. In this model, the micro-cylinder was exposed to a laminar flow with a known shear stress field in the leading region and a vortex flow in the trailing region. After surgery, the micro-cylinder was encapsulated by a thrombus-like tissue within one day, followed by SMC migration from the vena cava to the encapsulating tissue from day 3 to 20. SMC migration was time-dependent with a peak migration speed at day 5. At each given time (excluding day 1), blood shear stress exerts an inhibitory effect on SMC migration with significantly suppressed SMC migration in the laminar flow region than in the stagnation, separation, and vortex flow regions. SMCs were relatively parallel to the shear stress direction in high shear stress regions, whereas perpendicular to the shear stress direction in low shear stress regions. These results suggest that blood shear stress plays a role in regulating SMC migration and orientation in this model.

Animals↗

Risk assessment in patients with Ph+ chronic myelogenous leukemia at first relapse after allogeneic stem cell transplant: an EBMT retrospective analysis. The Chronic Leukemia Working Party of the European Group for Blood and Marrow Transplantation.

Patients with Ph+ chronic myelogenous leukemia who relapse after a first allogeneic stem cell transplant still have a possibility of long-term survival. To assess the value of the individual therapeutic options, the factors predicting outcome should be identified. We investigated data from 500 patients who relapsed before July 1996; follow-up was updated during 1998. The actuarial survival from relapse was 34.2% (95% confidence interval [CI]: 29. 9%-38.5%) at 5 years and 23.4% (95% CI: 18.9%-27.9%) at 10 years. Survival after relapse was significantly related to 5 factors: time from diagnosis to transplant (< 2 years vs >/= 2 years), disease phase at transplant (first chronic phase vs other), disease stage at relapse (cytogenetic or chronic phase vs advanced phase), time from transplant to relapse (< 1 year vs >/= 1 year), and donor type (HLA-identical sibling vs volunteer unrelated donor). The effects of individual adverse risk factors were cumulative: The probability of survival at 10 years decreased stepwise from 42% (0 factors), 32% (1 factor), 14% (2 factors), 3% (3 factors), to 0% (4 or 5 factors). Novel strategies for high-risk patients are warranted. We conclude that these 5 factors should be taken into account when comparing results of salvage therapies in patients with Ph+ chronic myeloid leukemia relapsing after allogeneic stem cell transplant.

Actuarial Analysis↗

Search for a 33.9 MeV/c(2) neutral particle in pion decay

The E815 (NuTeV) neutrino experiment has performed a search for a 33. 9 MeV/c(2) weakly interacting neutral particle produced in pion decay. Such a particle may be responsible for an anomaly in the timing distribution of neutrino interactions in the KARMEN experiment. E815 has searched for this particle's decays in an instrumented decay region; no evidence for this particle was found. The search is sensitive to pion branching ratios as low as 10(-13).

Journal Article↗

The immunosuppressive macrolide RAD inhibits growth of human Epstein-Barr virus-transformed B lymphocytes in vitro and in vivo: A potential approach to prevention and treatment of posttransplant lymphoproliferative disorders.

Whereas the standard immunosuppressive agents foster development of posttransplant lymphoproliferative disorders (PTLDs), the impact of RAD, a macrolide with potent immunosuppressive properties, and other immunosuppressive macrolides on these disorders remains undetermined. We found that RAD had a profound inhibitory effect on in vitro growth of six different PTLD-like Epstein-Barr virus+ lymphoblastoid B cell lines. Similar to normal T cells, RAD blocked cell-cycle progression in PTLD-like B cells in the early (G(0)/G(1)) phase. Furthermore, RAD increased the apoptotic rate in such cells. The drug also had a profound inhibitory effect on the growth of PTLD-like Epstein-Barr virus+ B cells xenotransplanted s.c. into SCID mice. The degree of the RAD effect varied among the three B cell lines tested and was proportional to its effects on the cell lines in vitro. In this in vivo xenotransplant model, RAD markedly delayed growth or induced regression of the established tumors. In one line, it was able to eradicate the tumor in four of eight mice. When RAD treatment was initiated before tumor cell injection, a marked inhibition of tumor growth was seen in all three lines. In two of them, the drug prevented tumor establishment in approximately 50% of mice (5/11 and 5/8). In summary, RAD is a potent inhibitor of PTLD-like cells in vitro and in vivo. These findings indicate that, in contrast to the standard immunosuppressive agents, macrolides such as RAD may be effective in prevention and treatment of PTLDs.

Animals↗

Vagus nerve stimulation: a new tool for brain research and therapy.

Biological psychiatry has a long history of using somatic therapies to treat neuropsychiatric illnesses and to understand brain function. These methods have included neurosurgery, electroconvulsive therapy, and, most recently, transcranial magnetic stimulation. Fourteen years ago researchers discovered that intermittent electrical stimulation of the vagus nerve produces inhibition of neural processes, which can alter brain electrical activity and terminate seizures in dogs. Since then, approximately 6000 people worldwide have received vagus nerve stimulation for treatment-resistant epilepsy. We review the neurobiology and anatomy of the vagus nerve and provide an overview of the vagus nerve stimulation technique. We also describe the safety and potential utility of vagus nerve stimulation as a neuroscience research tool and as a putative treatment for psychiatric conditions. Vagus nerve stimulation appears to be a promising new somatic intervention that may improve our understanding of brain function and has promise in the treatment of neuropsychiatric disorders.

Brain↗