bluuebunny/crossref_metadata_2025_split huggingface dataset:
Strengthening the Fellowship Training Experience: Findings from a National Survey of Fellowship Trained Geriatricians 1990–1998
Authors: Medina‐Walpole Annette , Barker William H. , Katz Paul R. 
Published: March 2004

Geriatric fellowship training has significantly advanced in the past 2 decades in number, organization, and accreditation of formal fellowship programs. A recent survey examined career decision‐making, fellowship training, and current professional activities of fellowship trained geriatricians. This paper focuses upon further desired fellowship training identified by these individuals. The responses reflect skills relevant to four aspects of professional performance: administration, management, clinical geriatrics, research, and education.More than half of the respondents documented the need for increased training in administration, including long‐term care medical directorship and Medicare/managed care. Regarding clinical training, 66% recommended additional subspecialty training, particularly in psychiatry, neurology, rehabilitation, and hospice/palliative care. Seventeen percent identified a need for training in research methodology, grant writing, and mentorship. Some 6% indicated a need for further training in education, citing teaching skills and program/faculty development.This article provides examples of opportunities to strengthen each of the four defined areas, including formal training in medical administration by the American Medical Director's Association, model strategies for incorporating subspecialties, hospice/palliative care, programs to pursue graduate level training in research at many universities, and faculty development programs such as those offered by Harvard and Stanford.Accredited geriatric fellowship programs as well as fellows should recognize potential gaps in training, and make available opportunities to strengthen these areas critical to preparing for future careers in geriatric medicine.
Aromatase Inhibitors: Current Indications and Future Prospects for Treatment of Postmenopausal Breast Cancer
Authors: Arora Amit , Potter Jane F. 
Published: March 2004

This article provides a comprehensive review of aromatase inhibitors (AIs) for geriatricians, because it appears that more elderly women will be using these drugs in the near future.Computerized literature searches of Medline were conducted through May 2003. Key words/phrases included in the literature searches were aromatase inhibitors, estrogen, and breast cancer. Limits included English language, age 65 and older, and female sex. All relevant articles were selected and reviewed. AIs suppress intratumoral and plasma estrogen levels significantly. Third‐generation AIs have excellent pharmacological profiles, with no significant drug interactions and better tolerability. These drugs have shown superiority compared with conventional therapies. The results of anastrozole, tamoxifen, and combination trials favors anastrozole over tamoxifen for adjuvant treatment, but further follow‐up is required. AIs are approved for the treatment of advanced metastatic breast cancer (BC) in postmenopausal women whose disease has progressed during tamoxifen therapy. Recent trials have shown that the highly selective third‐generation AIs are effective when used as first‐line therapy in metastatic BC. Their possible use in preventive, adjuvant, and neoadjuvant settings is also being explored.
Chromatic and spatial properties of parvocellular cells in the lateral geniculate nucleus of the marmoset (Callithrix jacchus)
Authors: Blessing Esther M. , Solomon Samuel G. , Maziar Hashemi‐Nezhad  , Morris Brian J. , Martin Paul R. 
Published: March 2004

The parvocellular (PC) division of the afferent visual pathway is considered to carry neuronal signals which underlie the red–green dimension of colour vision as well as high‐resolution spatial vision. In order to understand the origin of these signals, and the way in which they are combined, the responses of PC cells in dichromatic (‘red–green colour‐blind’) and trichromatic marmosets were compared. Visual stimuli included coloured and achromatic gratings, and spatially uniform red and green lights presented at varying temporal phases and frequencies.The sensitivity of PC cells to red–green chromatic modulation was found to depend primarily on the spectral separation between the medium‐ and long‐wavelength‐sensitive cone pigments (20 or 7 nm) in the two trichromatic marmoset phenotypes studied. The temporal frequency dependence of chromatic sensitivity was consistent with centre–surround interactions. Some evidence for chromatic selectivity was seen in peripheral PC cells. The receptive field dimensions of parvocellular cells were similar in dichromatic and trichromatic animals, but the achromatic contrast sensitivity of cells was slightly higher (by about 30%) in dichromats than in trichromats. These data support the hypothesis that the primary role of the PC is to transmit high‐acuity spatial signals, with red–green opponent signals appearing as an additional response dimension in trichromatic animals.
Some observations on the measurement of haemoglobin A2and S percentages by high performance liquid chromatography in the presence and absence of α thalassaemia
Authors: Head C E , Conroy M , Jarvis M , Phelan L , Bain B J 
Published: March 2004

Aims:To assess the accuracy and precision of measuring haemoglobin A2by high performance liquid chromatography (HPLC) in the presence and absence of sickle cell trait, with or without α thalassaemia trait.Methods:The haemoglobin A2percentage and the haemoglobin A2plus S percentages were determined by HPLC on 82 normal controls and 78 patients with sickle cell trait, respectively; the α thalassaemia status of each patient was determined by polymerase chain reaction. Red cell indices and haemoglobin A2and S percentages were compared in patients with two, three, or four α genes.Results:Of the 78 patients with sickle cell trait, 17 were heterozygous for α+thalassaemia (−α3.7/αα) and 13 were homozygous (−α3.7/−α3.7). Microcolumn chromatography showed that the haemoglobin A2percentage was slightly, but significantly, higher than normal in sickle cell trait. HPLC determinations of haemoglobin A2percentage in patients with sickle cell trait are precise but inaccurate, the percentage being appreciably overestimated. The measured haemoglobin A2percentage is stable for one week, but inaccuracy increases by two weeks in most samples. Despite this inaccuracy, there are significant differences in the HPLC “haemoglobin A2percentage” between groups of individuals with two, three, and four α genes.Conclusions:Haemoglobin A2determinations by HPLC are precise but inaccurate. Nevertheless, there are significant differences in the haemoglobin A2percentage in subjects with two, three, and four α genes. Although there is some overlap between groups, this can be useful, together with the red cell indices, in predicting the likelihood of coexisting α thalassaemia.
Parathyroid invasion, nodal recurrence, and lung metastasis by papillary carcinoma of the thyroid
Authors: Kakudo K , Tang W , Ito Y , Nakamura Y , Yasuoka H , Morita S , Miyauchi A 
Published: March 2004

Aims:Parathyroid invasion by papillary thyroid carcinoma (PTC) is found in a small proportion of surgical specimens, but the clinicopathological relevance of this phenomenon is not well understood. This study investigated the possible prognostic relevance of parathyroid invasion in PTC.Method:Parathyroid involvement was seen in 14 patients with PTC, and the clinicopathological characteristics and follow up data of these patients were analysed and compared with 164 patients without parathyroid involvement, in whom histological parathyroid examination had been undertaken, and 177 other patients without parathyroid examination (341 patients without parathyroid involvement in total).Results:Parathyroid invasion was found in older patients and there were more male patients in this group than in those without parathyroid invasion. These patients had more extrathyroid extension and were frequently in an advanced stage of disease. Lung metastasis was seen in two of the 14 patients, which was significantly more than that seen in control cases. Moreover, male patients with parathyroid invasion and those who were older than 55 years had reduced disease free survival compared with those without parathyroid invasion.Conclusion:Parathyroid invasion seen in thyroid carcinoma may be an important histological feature indicating a greater chance of nodal recurrence and lung metastasis.
Localisation of members of the vascular endothelial growth factor (VEGF) family and their receptors in human atherosclerotic arteries
Authors: Belgore F , Blann A , Neil D , Ahmed A S , Lip G Y H 
Published: March 2004

Background:Vascular endothelial growth factor (VEGF) mediates endothelial cell mitogenesis and enhances vascular permeability. The existence of single or multiple VEGF isoforms and receptors suggests that these proteins may have overlapping but distinct functions, which may be reflected in their cell expression and distribution.Methods:The localisation of VEGFs A–C and their receptors (VEGFRs 1–3, respectively) in 30 fresh human atherosclerotic arteries, 15 normal uterine arteries, and 15 saphenous veins using immunohistochemistry and western blotting.Results:Saphenous veins showed no staining for VEGF-B or VEGFR-2. Smooth muscle cells (SMCs) showed the strongest staining for VEGF-A, VEGF-B, VEGFR-1, and VEGFR-2 in all specimens. Conversely, VEGFR-3 and VEGF-C were predominately localised to the endothelial vasa vasorum in normal arteries, whereas medial SMCs showed the strongest staining in atherosclerotic arteries. Western blotting showed variations in VEGF protein localisation, with lower amounts of VEGF-B and VEGF-C in saphenous veins, compared with arterial tissue. Amounts of VEGF-C were lower than those of VEGF-A and VEGF-B in all specimens.Conclusion:This study provides direct evidence of the presence of VEGF proteins and receptors in human physiology and pathology, with variations in both the amounts of VEGF proteins expressed and their cellular distribution in normal arteries compared with atherosclerotic arteries. The presence of VEGFs A–C and their receptors in normal arterial tissue implies that VEGF functions may extend beyond endothelial cell proliferation. Reduced VEGFR-2 staining in atherosclerotic arteries may have implications for the atherosclerosis process and the development of vascular disease and its complications.
Sputum cytology of patients with severe acute respiratory syndrome (SARS)
Authors: Tse G M K , Hui P-K , Ma T K F , Lo A W I , To K-F , Chan W Y , Chow L T C , Ng H-K 
Published: March 2004

Background:Severe acute respiratory syndrome (SARS) is a newly described form of atypical pneumonia linked to a novel coronavirus.Aims:To review the sputum cytology of 15 patients who fulfilled the World Health Organisation clinical criteria for SARS in an attempt to evaluate whether early diagnosis is feasible with routine sputum examination.Methods:All sputum samples from patients with SARS from the four major hospitals in Hong Kong were reviewed; abnormalities were sought in the cellular component, including abnormal numbers and morphology of the component cells compared with those from age matched controls taken over the same period one year ago.Results:Fifteen sputum samples from patients were compared with 25 control samples. In the patients with SARS, loose aggregates of macrophages were seen more frequently in the sputum. These macrophages frequently showed morphological changes, such as cytoplasmic foaminess, vacuole formation, and nuclear changes (including multinucleation and a ground glass appearance) when compared with the control samples.Conclusions:The cytological features of SARS are non-specific, but the observation of any of the described features should prompt further investigations, especially in patients with suspicious clinical features.
Pulmonary pathological features in coronavirus associated severe acute respiratory syndrome (SARS)
Authors: Tse G M-K , To K-F , Chan P K-S , Lo A W I , Ng K-C , Wu A , Lee N , Wong H-C , Mak S-M , Chan K-F , Hui D S C , Sung J J-Y , Ng H-K 
Published: March 2004

Background:Severe acute respiratory syndrome (SARS) became a worldwide outbreak with a mortality of 9.2%. This new human emergent infectious disease is dominated by severe lower respiratory illness and is aetiologically linked to a new coronavirus (SARS-CoV).Methods:Pulmonary pathology and clinical correlates were investigated in seven patients who died of SARS in whom there was a strong epidemiological link. Investigations include a review of clinical features, morphological assessment, histochemical and immunohistochemical stainings, ultrastructural study, and virological investigations in postmortem tissue.Results:Positive viral culture for coronavirus was detected in most premortem nasopharyngeal aspirate specimens (five of six) and postmortem lung tissues (two of seven). Viral particles, consistent with coronavirus, could be detected in lung pneumocytes in most of the patients. These features suggested that pneumocytes are probably the primary target of infection. The pathological features were dominated by diffuse alveolar damage, with the presence of multinucleated pneumocytes. Fibrogranulation tissue proliferation in small airways and airspaces (bronchiolitis obliterans organising pneumonia-like lesions) in subpleural locations was also seen in some patients.Conclusions:Viable SARS-CoV could be isolated from postmortem tissues. Postmortem examination allows tissue to be sampled for virological investigations and ultrastructural examination, and when coupled with the appropriate lung morphological changes, is valuable to confirm the diagnosis of SARS-CoV, particularly in clinically unapparent or suspicious but unconfirmed cases.
Immune evasion proteins of human cytomegalovirus do not prevent a diverse CD8+ cytotoxic T-cell response in natural infection
Authors: Manley Thomas J. , Luy Lisa , Jones Thomas , Boeckh Michael , Mutimer Helen , Riddell Stanley R. 
Published: March 2004

AbstractAlthough cytomegalovirus (CMV) expresses proteins that interfere with antigen presentation by class I major histocompatibility complex (MHC) molecules, CD8+ cytotoxic T cells (CTLs) are indispensable for controlling infection and maintaining latency. Here, a cytokine flow cytometry assay that employs fibroblasts infected with a mutant strain of CMV (RV798), which is deleted of the 4 viral genes that are responsible for interfering with class I MHC presentation, was used to examine the frequency and specificity of the CD8+ CTLs to CMV in immunocompetent CMV-seropositive individuals. A large fraction of the CD8+ CTL response was found to be specific for viral antigens expressed during the immediate early and early phases of virus replication and presented by fibroblasts infected with RV798 but not wild-type CMV. These results demonstrate that the inhibition of class I antigen presentation observed in CMV-infected cells in vitro is not sufficient to prevent the induction of a broad repertoire of CD8+ CTLs after natural infection in vivo. Thus, reconstitution of T-cell immunity in immunodeficient patients by cell therapy or by vaccination may need to target multiple viral antigens to completely restore immunologic control of CMV.
Expression, localization, and regulation of NOS in human mast cell lines: effects on leukotriene production
Authors: Gilchrist Mark , McCauley Scott D. , Befus A. Dean 
Published: March 2004

AbstractNitric oxide (NO) is a potent radical produced by nitric oxide synthase (NOS) and has pleiotrophic activities in health and disease. As mast cells (MCs) play a central role in both homeostasis and pathology, we investigated NOS expression and NO production in human MC populations. Endothelial NOS (eNOS) was ubiquitously expressed in both human MC lines and skin-derived MCs, while neuronal NOS (nNOS) was variably expressed in the MC populations studied. The inducible (iNOS) isoform was not detected in human MCs. Both growth factor-independent (HMC-1) and -dependent (LAD 2) MC lines showed predominant nuclear eNOS protein localization, with weaker cytoplasmic expression. nNOS showed exclusive cytoplasmic localization in HMC-1. Activation with Ca2+ ionophore (A23187) or IgE-anti-IgE induced eNOS phosphorylation and translocation to the nucleus and nuclear and cytoplasmic NO formation. eNOS colocalizes with the leukotriene (LT)-initiating enzyme 5-lipoxygenase (5-LO) in the MC nucleus. The NO donor, S-nitrosoglutathione (SNOG), inhibited, whereas the NOS inhibitor, NG-nitro-l-arginine methyl ester (L-NAME), potentiated LT release in a dose-dependent manner. Thus, human MC lines produce NO in both cytoplasmic and nuclear compartments, and endogenously produced NO can regulate LT production by MCs. (Blood. 2004;104: 462-469)
Complete remission of TEL-PDGFRB–induced myeloproliferative disease in mice by receptor tyrosine kinase inhibitor SU11657
Authors: Cain Jennifer A. , Grisolano Jay L. , Laird A. Douglas , Tomasson Michael H. 
Published: March 2004

Abstract
The TEL-PDGFRB fusion oncogene is associated with chronic myelomonocytic leukemia (CMML) and results in the expression of a constitutively active tyrosine kinase. SU11657 is a multitargeted selective inhibitor of class III/V receptor tyrosine kinases, including the platelet-derived growth factor (PDGF) and vascular endothelial growth factor (VEGF) receptors KIT and FLT3. SU11657 inhibited TEL/PDGFβR kinase activity at nanomolar concentrations and inhibited TELPDGFRB-mediated factor-independent growth in myeloblastic 32D cells. Daily oral administration of SU11657 at 40 mg/kg suppressed myeloproliferation and significantly prolonged survival in TELPDGFRB mice treated prior to disease development, as well as in those with large tumor burdens. Our findings suggest that SU11657 or similar agents may have therapeutic potential in humans with hematologic malignancies expressing PDGFR fusion oncogenes. (Blood. 2004;104:561-564)
Monoclonal antibody IAC-1 is specific for activated α2β1 and binds to amino acids 199 to 201 of the integrin α2 I-domain
Authors: Schoolmeester Anne , Vanhoorelbeke Karen , Katsutani Shinya , Depraetere Hilde , Feys Hendrik B. , Heemskerk Johan M. W. , Hoylaerts Marc F. , Deckmyn Hans 
Published: March 2004

AbstractIn this study we describe the first monoclonal antibody, integrin activated conformation-1 (IAC-1), to recognize the active form of the platelet-collagen receptor, the integrin α2β1. IAC-1 has the following properties: (1) IAC-1 fails to bind to resting platelets but readily interacts with platelets stimulated by the glycoprotein VI-specific agonist, convulxin, and by other agonists; (2) similar concentration response relationships for binding of IAC-1 and soluble collagen were observed in convulxin-stimulated platelets; (3) the epitope for IAC-1 is T199Y200K201, which is located at the opposite site of the metal ion-dependent adhesion site in a region not involved in the I-domain “shifts” that occur upon ligand binding; (4) IAC-1 strongly binds to recombinant α2 I-domain, therefore suggesting that the neo-epitope appears to be exposed by an “unmasking” of I-domain-covering regions upon activation; (5) IAC-1 binds to platelets during adhesion to collagen under shear conditions, demonstrating activation of α2β1; (6) as IAC-1 does not interfere with platelet-collagen binding, it defines a new class of antibodies that is distinct from those belonging to the “cation- and ligand-induced binding sites” (CLIBSs) and the “ligand mimetic” group. These characteristics make IAC-1 a very powerful tool to study α2β1 activation under dynamic and physiologically relevant conditions. (Blood. 2004;104:390-396)
The peripheral cannabinoid receptor Cb2, frequently expressed on AML blasts, either induces a neutrophilic differentiation block or confers abnormal migration properties in a ligand-dependent manner
Authors: Alberich Jordà Meritxell , Rayman Nazik , Tas Marjolein , Verbakel Sandra E. , Battista Natalia , van Lom Kirsten , Löwenberg Bob , Maccarrone Mauro , Delwel Ruud 
Published: March 2004

AbstractCb2, the gene encoding the peripheral cannabinoid receptor, is located in a common virus integration site and is overex-pressed in retrovirally induced murine myeloid leukemias. Here we show that this G protein-coupled receptor (GPCR) is also aberrantly expressed in a high percentage of human acute myeloid leukemias. We investigated the mechanism of transformation by Cb2 and demonstrate that aberrant expression of this receptor on hematopoietic precursor cells results in distinct effects depending on the ligand used. Cb2-expressing myeloid precursors migrate upon stimulation by the endocannabinoid 2-arachidonoylglycerol and are blocked in neutrophilic differentiation upon exposure to another ligand, CP55940. Both effects depend on the activation of Gαi proteins and require the mitogen-induced extracellular kinase/extracellular signal-regulated kinase (MEK/ERK) pathway. Down-regulation of cyclic adenosine monophosphate (cAMP) levels upon Gαi activation is important for migration induction but is irrelevant for the maturation arrest. Moreover, the highly conserved G protein-interacting DRY motif, present in the second intracellular loop of GPCRs, is critical for migration but unimportant for the differentiation block. This suggests that the Cb2-mediated differentiation block requires interaction of Gαi proteins with other currently unknown motifs. This indicates a unique mechanism by which a transforming GPCR, in a ligand-dependent manner, causes 2 distinct oncogenic effects: altered migration and block of neutrophilic development. (Blood. 2004;104:526-534)
Prognostication of survival using cardiac troponins and N-terminal pro-brain natriuretic peptide in patients with primary systemic amyloidosis undergoing peripheral blood stem cell transplantation
Authors: Dispenzieri Angela , Gertz Morie A. , Kyle Robert A. , Lacy Martha Q. , Burritt Mary F. , Therneau Terry M. , McConnell Joseph P. , Litzow Mark R. , Gastineau Dennis A. , Tefferi Ayalew , Inwards David J. , Micallef Ivana N. , Ansell Stephen M. , Porrata Luis F. , Elliott Michelle A. , Hogan William J. , Rajkumar S. Vincent , Fonseca Rafael , Greipp Philip R. , Witzig Thomas E. , Lust John A. , Zeldenrust Steven R. , Snow Denise S. , Hayman Susan R. , McGregor Christopher G. A. , Jaffe Allan S. 
Published: March 2004

AbstractPrimary systemic amyloidosis (AL) is a fatal plasma cell disorder. Pilot data suggest survival is better in patients undergoing peripheral blood stem cell transplantation (PBSCT), but the selection process makes the apparent benefit suspect. We have reported that circulating cardiac biomarkers are the best predictors of survival outside of the transplantation setting. We now test whether cardiac troponins (cTnT and cTnI) and N-terminal pro-brain natriuretic peptide (NT-proBNP) are prognostic in transplant recipients. In 98 patients with AL undergoing PBSCT, serum cardiac biomarkers were measured (cTnT, 98 patients; cTnI, 65 patients; and NT-proBNP, 63 patients). Elevated levels of cTnT, cTnI, and NT-proBNP were present in 14%, 43%, and 48% of patients, respectively. At 20 months median follow-up, median survival has not been reached for patients with values below the thresholds; in patients with values above the thresholds, median survival is 26.1 months, 66.1 months, and 66.1 months, respectively. Our previously reported risk systems incorporating these markers were also prognostic, notably the cTnT/NT-proBNP staging. Using this system, 49%, 38%, and 13% of patients were in stage I, stage II, and stage III, respectively. Determining levels of circulating biomarkers may be the most powerful tool for staging patients with AL undergoing PBSCT.