Search PubMed⌕ Search

Biomedical subjects

V T Chang

Publications and source records attributed to V T Chang.

At least 19 recordsLinked to original sources
PubMed2006

Eukaryotic expression: developments for structural proteomics.

The production of sufficient quantities of protein is an essential prelude to a structure determination, but for many viral and human proteins this cannot be achieved using prokaryotic expression systems. Groups in the Structural Proteomics In Europe (SPINE) consortium have developed and implemented high-throughput (HTP) methodologies for cloning, expression screening and protein production in eukaryotic systems. Studies focused on three systems: yeast (Pichia pastoris and Saccharomyces cerevisiae), baculovirus-infected insect cells and transient expression in mammalian cells. Suitable vectors for HTP cloning are described and results from their use in expression screening and protein-production pipelines are reported. Strategies for co-expression, selenomethionine labelling (in all three eukaryotic systems) and control of glycosylation (for secreted proteins in mammalian cells) are assessed.

Animals↗
PubMed2003

Substance p-fibronectin-cytokine interactions in myeloproliferative disorders with bone marrow fibrosis.

Bone marrow (BM) fibrosis could occur secondarily to several clinical disorders: hematological and nonhematological. Clinical presentation of fibrosis could occur in myeloproliferative diseases, lymphoma, myelodysplastic syndrome and myeloma. The pathophysiology underlying BM fibrosis remains unclear despite intensive study, with a corresponding lack of specific therapy. This review discusses new insights in the role of substance P, cytokines and fibronectin in the development of BM fibrosis. Substance P is a neuropeptide that possesses pleiotropic properties, e.g. neurotransmission and immune/hematopoietic modulation and is linked to BM fibrosis. Cytokines and growth factors, in particular those associated with fibrogenic properties, e.g. TGF-beta, IL-1 and platelet-derived growth factor, are linked to BM fibrosis. Extracellular matrix proteins are increased in patients with BM fibrosis. Fibronectin in the sera of patients with BM fibrosis is complexed to substance P. Fibronectin appears to protect substance P from degradation by endogenous peptidases. This review describes the preliminary findings on the colocalization of substance P and fibronectin in the BM of patients with fibrosis. These data are reviewed in the context of published reports with particular focus on the relevant cytokines. A more detailed understanding of intra- and intercellular mechanisms in BM fibrosis may lead to effective therapy.

Cytokines↗
PubMed2001

Mimicry between neurokinin-1 and fibronectin may explain the transport and stability of increased substance P immunoreactivity in patients with bone marrow fibrosis.

Bone marrow (BM) fibrosis may occur in myeloproliferative diseases, lymphoma, myelodysplastic syndrome, myeloma, and infectious diseases. In this study, the role of substance P (SP), a peptide with pleiotropic functions, was examined. Some of its functions-angiogenesis, fibroblast proliferation, and stimulation of BM progenitors-are amenable to inducing BM fibrosis. Indeed, a significant increase was found in SP-immunoreactivity (SP-IR) in the sera of patients with BM fibrosis (n = 44) compared with the sera of patients with hematologic disorders and no histologic evidence of fibrosis (n = 46) (140 +/-12 vs 18 +/-3; P <.01). Immunoprecipitation of sera SP indicated that this peptide exists in the form of a complex with other molecule(s). It was, therefore, hypothesized that SP might be complexed with NK-1, its natural receptor, or with a molecule homologous to NK-1. To address this, 3 cDNA libraries were screened that were constructed from pooled BM stroma or mononuclear cells with an NK-1 cDNA probe. A partial clone (clone 1) was retrieved that was 97% homologous to the ED-A region of fibronectin (FN). Furthermore, sequence analyses indicated that clone 1 shared significant homology with exon 5 of NK-1. Immunoprecipitation and Western blot analysis indicated co-migration of SP and FN in 27 of 31 patients with BM fibrosis. Computer-assisted molecular modeling suggested that similar secondary structural features between FN and NK-1 and the relative electrostatic charge might explain a complex formed between FN (negative) and SP (positive). This study suggests that SP may be implicated in the pathophysiology of myelofibrosis, though its role would have to be substantiated in future research. (Blood. 2001;97:3025-3031)

Adult↗
PubMed2001

Video-assisted thoracoscopic sympathectomy-splanchnicectomy for pancreatic cancer pain.

Patients with unresectable pancreatic cancer often suffer severe pain. Various techniques are available for pain control. We present a patient with pancreatic cancer who underwent unilateral video-assisted thoracoscopic sympathectomy-splanchnicectomy and had complete pain relief. This minimally invasive procedure offers promise in carefully selected patients with severe pain from pancreatic cancer and other conditions which are not amenable to conventional interventions.

Adenocarcinoma↗
PubMed2000

The role of physical proximity in nosocomial diarrhea.

To examine physical proximity as a risk factor for the nosocomial acquisition of Clostridium difficile-associated diarrhea (CDAD) and of antibiotic-associated diarrhea (AAD), we assessed a retrospective cohort of 2859 patients admitted to a community hospital from 1 March 1987 through 31 August 1987. Of these patients, 68 had nosocomial CDAD and 54 had nosocomial AAD. In multivariate analysis, physical proximity to a patient with CDAD (relative risk [RR], 1.86; 95% confidence interval [CI], 1.06-3.28), exposure to clindamycin (RR, 4.22; 95% CI, 2.11-8.45), and the number of antibiotics taken (RR, 1.49; 95% CI, 1.23-1.81) were significant. For patients with nosocomial AAD, exposure to a roommate with AAD (RR, 3.94; 95% CI, 1. 27-12.24), a stay in an intensive care unit or cardiac care unit (RR, 1.93; 95% CI, 1.05-3.53), and the number of antibiotics taken (RR, 2.01; 95% CI, 1.67-2.40) were significant risk factors. Physical proximity may be an independent risk factor for acquisition of nosocomial CDAD and AAD.

Adult↗
PubMed2000

The memorial symptom assessment scale short form (MSAS-SF).

BACKGROUND: The Memorial Symptom Assessment Scale Short Form (MSAS-SF), an abbreviated version of the Memorial Symptom Assessment Scale, measures each of 32 symptoms with respect to distress or frequency alone. A physical symptom subscale (PHYS), psychologic symptom subscale (PSYCH), and global distress index (GDI) can be derived from the Short Form. We validated the MSAS-SF in a population of cancer patients. METHODS: Two hundred ninety-nine cancer patients examined at the Section of Hematology/Oncology completed the MSAS-SF and the Functional Assessment Cancer Therapy (FACT-G). The Karnofsky performance status (KPS), extent of disease (EOD), and demographic data were assessed. The Cronbach alpha coefficient was used to assess internal reliability. MSAS-SF subscales were assessed against subscales of the FACT-G, the KPS, and EOD to determine criterion validity. Test-retest analysis was performed at 1 day and at 1 week. RESULTS: The Cronbach alpha coefficients for the MSAS-SF subscales ranged from 0.76 to 0.87. The MSAS-SF subscales showed convergent validity with FACT subscales. Correlation coefficients were -0.74 (P < 0.001) for the PHYS and FACT-G physical well-being subscales, -0.68 (P < 0.001) for the PSYCH and FACT emotional well-being subscales, and -0.70 (P < 0.001) for GDI and FACT summary of quality-of-life subscales. The MSAS-SF subscales demonstrated convergent validity with performance status, inpatient status, and extent of disease. The test-retest correlation coefficients for the MSAS-SF subscales ranged from 0.86 to 0.94 at 1 day and from 0.40 to 0.84 for the 1 week group. CONCLUSIONS: The MSAS-SF is a valid and easy to use instrument for symptom assessment.

Adult↗
PubMed2000

Validation of the Edmonton Symptom Assessment Scale.

BACKGROUND: The Edmonton Symptom Assessment Scale (ESAS) is a nine-item patient-rated symptom visual analogue scale developed for use in assessing the symptoms of patients receiving palliative care. The purpose of this study was to validate the ESAS in a different population of patients. METHODS: In this prospective study, 240 patients with a diagnosis of cancer completed the ESAS, the Memorial Symptom Assessment Scale (MSAS), and the Functional Assessment Cancer Therapy (FACT) survey, and also had their Karnofsky performance status (KPS) assessed. An additional 42 patients participated in a test-retest study. RESULTS: The ESAS "distress" score correlated most closely with physical symptom subscales in the FACT and the MSAS and with KPS. The ESAS individual item and summary scores showed good internal consistency and correlated appropriately with corresponding measures from the FACT and MSAS instruments. Individual items between the instruments correlated well. Pain ratings in the ESAS, MSAS, and FACT correlated best with the "worst-pain" item of the Brief Pain Inventory (BPI). Test-retest evaluation showed very good correlation at 2 days and a somewhat smaller but significant correlation at 1 week. A 30-mm visual analogue scale cutoff point did not uniformly distinguish severity of symptoms for different symptoms. CONCLUSIONS: For this population, the ESAS was a valid instrument; test-retest validity was better at 2 days than at 1 week. The ESAS "distress" score tends to reflect physical well-being. The use of a 30-mm cutoff point on visual analogue scales to identify severe symptoms may not always apply to symptoms other than pain.

Activities of Daily Living↗
PubMed2000

Symptom and quality of life survey of medical oncology patients at a veterans affairs medical center: a role for symptom assessment.

BACKGROUND: The current study was conducted to assess symptom prevalence and symptom intensity and their relation to quality of life in medical oncology patients at a Veterans Affairs medical center. METHODS: Consecutive inpatients and outpatients were asked to complete the Functional Assessment Cancer Therapy (FACT-G), Memorial Symptom Assessment Scale (MSAS), and the Brief Pain Inventory. Symptoms then were analyzed by their relation to Karnofsky performance status (KPS) and quality of life. RESULTS: Two hundred forty patients participated. The median number of symptoms was 8 per patient (range, 0-30 symptoms). The 5 most prevalent symptoms were lack of energy (62%), pain (59%), dry mouth (54%), shortness of breath (50%), and difficulty sleeping (45%). Patients with moderate intensity pain had a median number of 11 symptoms and patients with moderate intensity lack of energy had a median number of 13 symptoms. The number of intense symptoms increased as the KPS decreased (P < 0.001). Patients with moderately intense pain or fatigue also were more likely to experience nausea, dyspnea, and lack of appetite. The number of symptoms rated as present on the MSAS was found to correlate significantly with the FACT-G Sum Quality of Life score. CONCLUSIONS: Intense symptoms were highly prevalent in this population. The presence of pain, lack of energy, or poor performance status should lead to comprehensive symptom assessment. Patients free of disease nevertheless still may experience intense symptoms. The number of symptoms present may be a helpful guide to quality of life. Routine comprehensive symptom assessment may identify a significant fraction of patients who urgently require intensive symptom palliation.

Activities of Daily Living↗
PubMed1998

Quality of life and survival: the role of multidimensional symptom assessment.

BACKGROUND: Recent data from clinical trials suggest that quality-of-life (QOL) measurements may independently predict survival. The relation between survival and QOL measurements was tested among 122 inpatients and 96 outpatients with malignancies at one of four sites (colon, breast, ovary, or prostate) who participated in a cross-sectional validation study of the Memorial Symptom Assessment Scale (MSAS), a measure of the frequency of, severity of, and distress caused by physical symptoms. METHODS: The relation between MSAS summary scores and survival was evaluated in a multivariate analysis that adjusted concurrently for other important covariates, such as age, site and extent of disease, inpatient status, Karnofsky performance status (KPS), and other QOL measurements. RESULTS: In the multivariate analysis, extent of disease (P < 0.0001), inpatient status (P=0.014), higher MSAS physical symptom subscale score (P=0.004), and lower KPS score (P=0.009) independently predicted decreased survival. Other QOL measurements did not contribute significantly to the model. CONCLUSIONS: The MSAS physical symptom subscale score significantly predicts survival and adds to the prognostic information provided by KPS and extent of disease. Patients may be under-assessed regarding both the number and the severity of symptoms. Measurements of physical symptoms and related distress offer additional prognostic information concerning the survival of patients with cancer and may account for the predictive value of QOL scores.

Adult↗
PubMed1998

Systemic transforming growth factor-beta in patients with bone marrow fibrosis--pathophysiological implications.

Idiopathic myelofibrosis (IMF) and secondary myelofibrosis (MF) are characterized by bone marrow (BM) fibrosis, neoangiogenesis, and increased extracellular matrix (ECM) proteins. These characteristics may be partially attributed to transforming growth factor beta (TGF-beta), a cytokine produced by monocytes. In myelofibrosis, monocytes are increased and activated with concomitant up-regulation of intracytoplasmic TGF-beta. We have therefore determined systemic TGF-beta in patients with either BM fibrosis: IMF, n = 18; MF, n = 16; or without BM fibrosis: hematologic disorders with normal platelets (n = 31); high platelets (n = 9); or normal controls (n = 27). Compared with nonfibrosis sera, there was significant TGF-beta elevation in BM fibrosis sera (P < 0.0001). Most (>80%) of the TGF-beta is active and belongs to the-beta1 isoform. In situ hybridization and immunohistochemical analyses in BM biopsy sections showed a marked increase in TGF-beta1 only in patients with fibrosis. Moreover, TGF-beta protein was detected mainly in myelomonocytic-like predominant areas. To determine if another functionally similar cytokine, basic fibroblast growth factor (bFGF), may be important to BM fibrosis, we quantitated sera levels and found elevation in 57% compared with 100% elevation for TGF-beta. The data indicate that irrespective of etiology, systemic TGF-beta is elevated in patients with BM fibrosis. TGF-beta likely plays an important role in the development of BM fibrosis. The study also provides a significant parameter for early therapeutic intervention in BM fibrosis.

Adult↗
PubMed1997

Increased phantom limb pain as an initial symptom of spinal-neoplasia.

Phantom limb pain is a common sequela of amputation. Studies suggest that over time, there is a decrease in frequency and intensity of phantom pain. Persistently increased phantom pain has been seen in benign lesions affecting the peripheral and central nervous system. We present a 74-year-old woman who had a left above-knee amputation for leiomyosarcoma of the foot 24 years previously. She had been free of disease and ambulated independently until 1 month before hospitalization, when she noted increasing pain in her phantom foot. At the time of admission, she had developed increasing low back pain and was diagnosed with adenocarcinoma of unknown primary. Work-up confirmed involvement of the L4 vertebral body with epidural and paraspinal disease. We believe this is the first reported case of worsening phantom limb pain resulting from a spinal metastasis. We review the literature on the potential implications of increased phantom pain.

Adenocarcinoma↗
PubMed1997

Intravenous phenytoin in the management of crescendo pelvic cancer-related pain.

Rapidly progressive pain, or "crescendo" pain, can be a difficult management problem. A cancer patient is presented who experienced crescendo neuropathic pain due to progressive pelvic disease. This patient reported significant pain relief with the administration of intravenous phenytoin. The case illustrates the type of therapeutic approach that may be considered for crescendo pain and highlights a potential role for intravenous phenytoin in the management of patients with crescendo cancer-related neuropathic pain.

Female↗
PubMed1996

Implication of CD44 in adhesion-mediated overproduction of TGF-beta and IL-1 in monocytes from patients with bone marrow fibrosis.

Myelofibrosis (MF) is characterized by bone marrow (BM) fibrosis and excessive deposits of extracellular matrix (ECM) proteins which include fibronectin (FN), collagen type I and hyaluronic acid (HA). We have previously reported that adhesion to polystyrene over-activates MF monocytes. We now confirm their activation by increased CD25 expression and tyrosine phosphorylation. We hypothesize that ECM protein-adhesion molecule interactions induce overproduction of fibrogenic cytokines in MF monocytes leading to BM fibrosis. In this study we found that FN, collagen type I and HA induce 2-3-fold more TGF-beta and 6-9 fold more interleukin (IL)-1 in MF monocytes than normal controls (NC). Since CD44 can function as the natural ligand for these proteins, its role was studied. We found that CD44 mediated most of the TGF-beta and IL-1 produced. Immunoprecipitation of CD44 revealed three proteins at approximately 11 kD in MF monocytes and one in NC. Our results indicated that adhesion is important in overproduction of TGF-beta and IL-1, and that their production is at least partly mediated by adhesion molecule-ECM protein interactions. These results implicate at least one adhesion molecule, CD44, in the pathophysiology of the BM fibrosis.

Adult↗
PubMed1992

Homocysteine and other sulfhydryl compounds enhance the binding of lipoprotein(a) to fibrin: a potential biochemical link between thrombosis, atherogenesis, and sulfhydryl compound metabolism.

We have previously shown that lipoprotein(a) [Lp(a)], an atherogenic lipoprotein that contains apolipoprotein(a), which shares partial structural homology to plasminogen, binds to a plasmin-modified fibrin surface, and we have postulated that this interaction may be atherogenic. Moderate elevations in blood homocysteine, a relatively common condition, predispose to premature atherosclerosis. The reasons for this are not established. We now report that homocysteine, at concentrations as low as 8 microM, significantly increases the affinity of Lp(a) for fibrin. Homocysteine induces a 20-fold increase in the affinity between Lp(a) and plasmin-treated fibrin and a 4-fold increase with unmodified fibrin. Lp(a) binding is inhibited by epsilon-aminocaproic acid, indicating lysine binding site specificity. Homocysteine does not enhance the binding of Lp(a) to other surface-bound proteins. Cysteine, glutathione, and N-acetylcysteine also increase the affinity between Lp(a) and fibrin. Homocysteine does not affect the binding of low density lipoprotein or plasminogen to fibrin, nor does it alter the gel-filtration elution pattern of Lp(a). Immunoblot analysis documents the fact that homocysteine partially reduces Lp(a). These results suggest that homocysteine alters the intact Lp(a) particle so as to increase the reactivity of the plasminogen-like apolipoprotein(a) portion of the molecule. The observation that sulfhydryl amino acids increase Lp(a) binding to fibrin suggests a biochemical relationship between sulfhydryl compound metabolism, thrombosis, and atherogenesis.

Blotting, Western↗
PubMed1991

Mycobacteremia in acquired immune deficiency syndrome. Rapid diagnosis based on inclusions in the peripheral blood smear.

In 16 cases of human immunodeficiency virus-associated Mycobacterium avium-intracellulare complex (MAC) infection, 7 were diagnosed after finding intracytoplasmic negatively staining linear inclusions within histiocytes using Romanowsky-stained bone marrow aspirate smears. Four patients had inclusions within monocytes and neutrophils in the peripheral blood smear. The authors believe these cases represent the first reported examples of MAC inclusions observed within leukocytes in Wright's-stained peripheral blood smears. Inclusions usually were found in the setting of prominent toxic changes in leukocytes such as large Dohle bodies, marked granulation, and vacuolation. These inclusions are characteristic of mycobacteria and can be confirmed by acid fast stains and mycobacteriologic culture. The authors present the clinical and laboratory setting in which identification of inclusions in peripheral blood smears may be a rapid, minimally invasive, and cost-effective method of diagnosing mycobacterial infection.

Acquired Immunodeficiency Syndrome↗
PubMed1989

The bias of the sample proportion following a group sequential phase II clinical trial.

Group sequential testing procedures have seen wide use in Phase II clinical trials. The sample proportion p of responders is the commonly used estimator for the binomial response probability p. It can be shown that p is the maximum likelihood estimator (MLE) of p. It is well known that MLE can be in general (Whitehead) and p in particular (Dupont) biased estimators, if ther computation follows a group sequential procedure. In this paper we numerically investigate the bias of p. We find that the magnitude of the bias of p is less than 0.025 in all cases we investigated. We apply the idea in Whitehead to propose a bias-adjusted estimator that reduces the bias substantially and reduces the mean square error as well in a certain range of p. We also evaluate the uniformly minimum variance unbiased (UMVU) estimator. If one does not mind a bias of 0.025, one may find the sample proportion a suitable estimator for p because of its simplicity and easy explanation. If one is concerned with bias, the bias-adjusted estimator may be a good choice.

Drug Evaluation↗