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Biomedical subjects

C B Wilson

Publications and source records attributed to C B Wilson.

At least 91 records · Page 5Linked to original sources
PubMed1997

Effect of sputum bacteriology on the quality of life of patients with bronchiectasis.

Bronchiectatic patients have impaired health-related quality of life (QoL) and are prone to chronic lower respiratory tract infections. We have investigated whether impaired QoL is related to sputum bacteriology. Eighty seven patients with non-cystic fibrosis (non-CF) bronchiectasis, in a stable phase of their illness, completed three QoL measures, underwent a computed tomography (CT) scan and lung function tests, and provided a fresh sputum sample for microscopy and culture. The QoL of patients colonized by Pseudomonas aeruginosa (Pa group) was significantly worse than all other patients grouped together (non-Pa group), and specifically those infected by Haemophilus influenzae (Hi group) or who had no bacterial growth (NG group) (p<0.05), but not those infected by other bacterial species (O group). The Pa group had worse lung function, but no significant differences were found between the groups for forced expiratory volume in one second (FEV1) and peak expiratory flow rate. The Pa group had significantly worse bronchiectasis scores than the O, NG and non-Pa groups, but not the Hi group. There were no significant differences between the groups with respect to the number of infective exacerbations in the last year, but the Pa group had significantly more hospital admissions. Patients infected by P. aeruginosa for more than 3 yrs had significantly worse FEV1 (p<0.03) and bronchiectasis scores (p<0.05) than those infected with P. aeruginosa for less time, but not significantly worse QoL. We conclude that, overall, patients infected with P. aeruginosa have worse quality of life, and that P. aeruginosa is associated with a greater extent of disease and worse lung function. Although patients infected with H. influenzae had extensive bronchiectasis their quality of life was better than the P. aeruginosa infected group.

Adult↗
PubMed1997

Long-term outcome in children and adolescents after transsphenoidal surgery for Cushing's disease.

Cushing's disease refers specifically to an ACTH-producing pituitary adenoma that stimulates excess cortisol production. Transsphenoidal surgery is the treatment of choice in children and adolescents, but disparate cure rates have been reported, ranging from 50-98%. The discrepancies in cure rate are due primarily to the technical success of the surgery and the length and method of follow-up. We studied 42 consecutive children and adolescents (age, < or = 18 yr) who underwent transsphenoidal exploration for the primary treatment of Cushing's disease at University of California-San Francisco from 1974-1993. Only 7 patients had persistent disease, defined as evidence of Cushing's disease within 6 months of surgery, yielding an initial remission rate of 83%. We comprehensively evaluated 26 of the 35 patients who experienced an initial remission, including testing of the ACTH-adrenocortical axis. The mean duration of follow-up is 7.2 yr (range, 1.5-13.6 yr). Seven experienced a relapse of Cushing's disease, yielding a net remission rate of 73%. Relapses occurred an average of 4.2 yr postoperatively (range, 0.75-6.2 yr). Five patients experienced relapse within 5 yr of surgery, whereas 2 relapsed more than 5 yr postoperatively. Repeat transsphenoidal surgery was performed in 8 patients with persistent or recurrent disease, and 6 of these remain in remission. Low serum or urinary cortisol measurements within the first post-operative week predicted remission of Cushing's disease, but were not necessarily predictive of long-term cure. Hypercortisolism had significant effects on bone metabolism, as reflected by both diminished bone density in the majority of patients examined and decreased growth rate. Both parameters improved after surgical care, although they did not fully normalize. We conclude that transsphenoidal surgery is a safe and effective treatment for pediatric Cushing's disease, but long-term surveillance is necessary to detect possible recurrences.

Adolescent↗
PubMed1997

Suppression of anti-glomerular basement membrane nephritis by administration of anti-monocyte chemoattractant protein-1 antibody in WKY rats.

Anti-glomerular basement membrane (GBM) nephritis in WKY rats is characterized by an accumulation of CD8-positive lymphocytes (CD8+ lym) and monocytes/macrophages (Mo/M psi) in the glomeruli and crescent formation. In the study presented here, the involvement of a chemokine for Mo/M psi, monocyte chemoattractant protein-1 (MCP-1), was examined in this model. An intense induction of mRNA for MCP-1 in the glomeruli and a suppressive effect of anti-MCP-1 antibody administration on the glomerular Mo/M psi accumulation and proteinuria were found. MCP-1 mRNA was expressed intensely in the glomeruli 4 d after the anti-GBM antibody injection. When MCP-1 was neutralized with anti-MCP-1 antibody administration, the number of Mo/M psi infiltrating in the glomeruli decreased by 34.7% (19.6 +/- 7.1 versus 30.0 +/- 6.0 per glomerular cross-section, P < 0.01) and proteinuria by 66.2% (15.6 +/- 9.3 versus 46.1 +/- 15.1 mg/d, P < 0.01) at day 4. In contrast, the number of CD8+ lym accumulating in the glomeruli was not affected significantly (6.6 +/- 2.7 versus 6.0 +/- 3.0 per glomerular cross-section, P > 0.05). However, the treatment with the anti-MCP-1 antibody did not reduce Mo/M psi infiltration, urinary protein excretion, and crescent formation at day 8. These data suggest that MCP-1 plays a role in the glomerular accumulation of Mo/M psi, and that the infiltrating Mo/M psi cause glomerular injury and increased excretion of protein in the urine.

Animals↗
PubMed1996

The proximal regulatory element of the interferon-gamma promoter mediates selective expression in T cells.

Interferon-gamma (IFN-gamma) is produced by natural killer cells and certain subsets of T cells, but the basis for its selective expression is unknown. Within the region between -108 and -40 base pairs of the IFN-gamma promoter are two conserved and essential regulatory elements, which confer activation-specific expression in T cells. This report describes studies indicating that the most proximal of these two regulatory elements is an important determinant of its restricted expression. The proximal element is a composite site that binds members of the CREB/ATF, AP-1, and octamer families of transcription factors. Jun is essential for activation-induced transcription and binds preferably as a heterodimer with ATF-2. In contrast, CREB appears to dampen transcription from this element. The CpG dinucleotide in this element is selectively methylated in Th2 T cells and other cells that do not express IFN-gamma, and methylation markedly reduces transcription factor binding. As a target for DNA methylation and for binding of transcription factors that mediate or impede transcription, this element appears to play a central role in controlling IFN-gamma expression.

Activating Transcription Factor 1↗
PubMed1996

Cloning of rat 92-kDa type IV collagenase and expression of an active recombinant catalytic domain.

A full-length cDNA for rat 92-kDa type IV collagenase was isolated and sequenced. RNase protection assay revealed tissue specific differential expression of the 92-kDa type IV collagenase in the rat during development. Natural and modified forms of the 92-kDa type IV collagenase were expressed. One active protein, 92-CD, contained only the putative catalytic domain. Large quantities of the 92-CD were expressed in Escherichia coli, extracted from inclusion bodies, purified, and refolded to an active form. This recombinant protein was able to cleave denatured and native collagen and was inactivated by known MMP inhibitors.

Amino Acid Sequence↗
PubMed1996

Bromodeoxyuridine labeling index in glioblastoma multiforme: relation to radiation response, age, and survival.

PURPOSE: Various measures of the rate of tumor cell proliferation have been found to predict survival in patients with intracerebral gliomas. We correlated the bromodeoxyuridine labeling index (BrdUrd LI) with the response to radiation therapy, survival, and known prognostic factors in a series of patients with glioblastoma multiforme (GM) to test its utility as a prognostic factor. METHODS AND MATERIALS: The BrdUrd LI was determined in 200 newly diagnosed intracranial GMs. Age and sex were known for all patients. The response to radiation therapy was determined in 116 patients by comparing neuroimaging studies obtained before and after external beam radiation therapy. Survival was analyzed in 64 patients who were treated according to two consecutive prospective clinical protocols. RESULTS: The median BrdUrd LI was 6.5% (mean, 7.2%; range, 1.1-25.4%). The BrdUrd LI did not correlate significantly with age, sex, radiation response, or survival. Age and Karnofsky performance score were independent prognostic factors in our cohort. CONCLUSION: The proliferative rate as measured by BrdUrd LI was not a prognostic factor in our GM cohort. The BrdUrd LI did not correlate significantly with known prognostic factors in GM. There was no significant relationship between BrdUrd LI and radiation response.

Adolescent↗
PubMed1996

Intervention of CD4+ cell subset shifts and autoimmunity in the BXSB mouse by murine CTLA4Ig.

In the BXSB autoimmune disease-prone mouse strain, male mice develop severe lupus-like symptoms and die early in life (4-6 mo), whereas females do not. We have previously demonstrated that profound phenotypic and functional changes occur with age in CD4+ cells from BXSB males. CD4+ cells from males (4 mo old) were predominantly CD44high, CD45RBlow, and MEL-14low (activated/memory phenotypes), while the reciprocal phenotypes characteristic of naive cells were prevalent in age-matched females and young adult males (2 mo old). CD4+ cells from older males proliferated less and produced less IL-2 and IFN-gamma than cells from either females or young males in response to immobilized anti-CD3 mAb. We tested the effect of CTLA4Ig treatment on the progression of disease in BXSB males. CD4+ cells from CTLA4Ig-treated mice at 4 mo of age were predominantly CD44low, CD45RBhigh, and MEL-14high phenotypes that were identical with those observed in CD4+ cells from young (3-mo-old) females. In contrast, control male mice treated with IgG2a accumulated the CD4+ memory phenotype. CD4+ cells from 4-mo-old male CTLA4Ig-treated mice proliferated and produced IL-2 at levels similar to those of cells from females in response to immobilized anti-CD3 mAb. Furthermore, in contrast to IgG2a-treated mice, female and CTLA4Ig-treated male mice at 4 mo of age produced no anti-chromatin Abs. Three of four male mice injected with CTLA4Ig until 6 mo of age appeared healthy at 8 mo of age, whereas all five of IgG2a-treated control males died by 6 mo of age. These 8-mo-old CTLA4Ig-treated males showed variable resistance to autoimmunity as well as function and phenotype marker expression, and a less striking glomerulonephritis than 4-mo-old untreated males. The results of this study demonstrate that the rampant T cell activation and T cell dysfunction that occur in male BXSB mice by 4 mo of age are abrogated by blocking the CTLA4-dependent costimulatory signal(s). They also show that treatment with CTLA4Ig can suppress the pathogenesis of disease and increase longevity.

Abatacept↗
PubMed1996

Extracellular matrix and integrin composition of the normal bladder wall.

We performed an immunohistochemistry study of the normal human bladder so as to understand the interactions of extracellular matrix (ECM) components and the integrins of cell adhesion that accommodate the volume changes and maintain an impermeable barrier to reabsorption of urine in the bladder. The normal human urothelial cell and/or its plasma membrane contained integrins alpha 3, alpha V, beta 1, and beta 4 but did not contain integrin beta 3. The urothelial basement membrane (UBM) contained collagen type IV and laminin. Fibronectin and integrins alpha 3 and beta 4 were found in or near the UBM area, with types I and III collagen and tenascin abutting the area. The patterns of collagen, laminin, tenascin, vitronectin, fobronectin, and the alpha 3, alpha V, beta 1, and beta 3 integrins in the lamina propria, vessels, nerves, and smooth-muscle layers are described. These findings detail the normal anatomical ECM/integrin relationship that provides the cellular basis for bladder-wall relationships responsible for its impermeable state and other functions.

Cells, Cultured↗
PubMed1996

The role of angiogenic factor bFGF in the development of dural AVFs.

PURPOSE: Dural arteriovenous fistulas (dAVFs) are known to be acquired disorders. Angiogenic stimulants, such as basic fibroblast growth factor (bFGF), may be involved in the evolution of this disorder. We examined the appearance and localization of bFGF, in human dAVF sinuses, versus a control using immunohistochemical techniques, to evaluate these qualitative differences. PATIENTS AND METHODS: Four human dural sinuses from dAVF patients, and one control dural sinus were removed at surgery or autopsy and used for this study. Immunohistochemistry for bFGF was performed in all five specimens to identify its appearance and localization. Immunohistochemistry for alpha smooth muscle actin, factor VII related antigen, and macrophage (CD-68) were done in all tissues to identify the bFGF positive cell types. RESULTS: In the control dural sinus, there was negative staining by bFGF immunohistochemistry. However, in all four sinuses of the dAVF patients, smooth muscle cells, endothelial cells, and meningeal cells were stained positively in various degrees by bFGF immunohistochemistry. CONCLUSION: bFGF may be significant in the development of dAVFs, judging from its strong immunoreactivity in the sinuses of dAVF patients.

Adult↗
PubMed1996

Interstitial pneumonitis as a late complication of high dose therapy with cyclophosphamide/thiotepa and peripheral blood progenitor cell rescue for carcinoma of the breast.

The incurability of metastatic breast cancer with conventional chemotherapy has prompted many units to investigate the role of high dose chemotherapy and autologous stem cell rescue in patients with advanced or poor risk primary disease. Although preliminary data from centres treating patients with these modalities are encouraging, both in terms of rapidity of haemopoietic recovery and progression free survival, there is nonetheless a procedure related toxicity. We describe a patient with inflammatory carcinoma of the breast who received high dose cyclophosphamide and thiotepa prior to peripheral blood progenitor cell rescue, and developed a steroid responsive interstitial pneumonitis 10 weeks after stem cell infusion.

Adenocarcinoma↗
PubMed1996

Evidence for a second function of the MA sequence in the Rous sarcoma virus Gag protein.

During retrovirus assembly, Gag proteins bind to the inner leaflet of the plasma membrane to initiate the budding process. The molecular basis of this protein-lipid interaction is poorly understood. For the human, immunodeficiency virus type 1 Gag protein, we recently reported that the membrane-binding domain resides within the N-terminal 31 amino acids and consists of two components: myristate and a cluster of basic residues, which together promote membrane binding in vitro and budding in vivo (W. Zhou, L. J. Parent, J. W. Wills, and M. D. Resh, J. Virol. 68:2556-2569, 1994). The positively charged residues associate electrostatically with acidic phospholipids to stabilize membrane binding, while myristate provides membrane-binding energy via hydrophobic interactions. Here we demonstrate that the human immunodeficiency virus type 1 Gag membrane-binding domain can fully replace the membrane-targeting function of the N-terminal 100 residues of the non-myristylated Rous sarcoma virus (RSV) Gag protein. To further explore the importance of myristate and basic residues in membrane binding, we developed a gain-of-function assay whereby budding was restored to defective mutants of RSV Gag. Detailed mutational analysis revealed that the position, number, and context of charged residues are crucial to budding. Myristate provides additional membrane-binding energy, which is critical when a Gag protein is near the threshold of stable membrane association. Finally, viruses with altered matrix (MA) proteins that are noninfectious, even though they produce particles with high efficiency, were identified. Thus, we present the first evidence that the RSV MA sequence plays two distinct roles, membrane binding during particle assembly and a second, as yet undefined function required for viral infectivity.

Amino Acid Sequence↗
PubMed1996

Venous angiography is needed to interpret inferior petrosal sinus and cavernous sinus sampling data for lateralizing adrenocorticotropin-secreting adenomas.

Bilateral simultaneous venous sampling of ACTH from the inferior petrosal sinus is a reliable test for diagnosing Cushing's disease, but is not reliable for lateralizing ACTH-secreting pituitary adenomas. We reviewed 23 consecutive patients with Cushing's disease who underwent venous angiography of the cavernous and inferior petrosal sinuses followed by bilateral simultaneous venous sampling of ACTH in the inferior petrosal and cavernous sinuses. Venous drainage was bilaterally symmetric in 14 patients (61%) and asymmetric in 9 (39%). The most common asymmetric pattern (6 patients) was for blood from both cavernous sinuses to drain into the right inferior petrosal sinus, with no significant drainage into the left. Cavernous sinus sampling in 21 patients correctly lateralized the tumor in 12 cases of symmetric venous drainage, but in only 3 cases of asymmetric drainage. Inferior petrosal sinus sampling in all 23 patients correctly lateralized the tumor in 12 cases of symmetric drainage, but in only four cases of asymmetric drainage. Overall, venous sampling correctly lateralized 70% of the tumors. Incorrect lateralization in cases of asymmetric venous drainage is probably attributable to shunting of blood toward the side of dominant venous drainage. Our findings illustrate the need for venography in all patients undergoing venous sampling of ACTH because an understanding of the venous drainage patterns is essential to correctly interpret venous sampling data and warn physicians that the lateralization data may be incorrect or unreliable.

Adenoma↗