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Biomedical subjects

C B Wilson

Publications and source records attributed to C B Wilson.

At least 127 records · Page 7Linked to original sources
PubMed1995

Involvement of reactive oxygen intermediates in cyclooxygenase-2 expression induced by interleukin-1, tumor necrosis factor-alpha, and lipopolysaccharide.

Reactive oxygen intermediates (ROIs) play an important role in inflammatory processes as mediators of injury and potentially in signal transduction leading to gene expression. Cyclooxygenase (COX) is a rate-limiting enzyme in prostanoid biosynthesis, and its recently cloned inducible form, COX-2, is induced by proinflammatory cytokines. This study linked ROIs to the signaling pathways that induce COX-2 expression. The hydroxyl radical scavengers DMSO (1%), as well as di- and tetramethylthiourea, inhibited IL-1-, TNF alpha-, and LPS-induced COX-2 expression in rat mesangial cells. The suppression of COX-2 mRNA expression correlated with the COX-2 protein level. In comparison with the prolonged induction of the inducible gene encoding protein-tyrosine phosphatase by hydrogen peroxide, the COX-2 gene was only transiently induced. Protein-tyrosine phosphatase is also induced by heat shock and chemical stress, whereas COX-2 is not. Superoxide was a more potent inducer for COX-2 than hydrogen peroxide. In addition, NADPH stimulated COX-2 expression, and an inhibitor of NADPH oxidase blocked COX-2 expression induced by TNF alpha. COX-2 and KC gene expression costimulated by IL-1 were inhibited differentially by the scavengers. These studies demonstrate that oxidant stress is a specific and important inducer of COX-2 gene expression. This induction may contribute to the deleterious amplification of prostanoids in inflammation and compound the direct effects of ROI production.

Animals↗
PubMed1995

Extrasellar, intracavernous sinus adrenocorticotropin-releasing adenoma causing Cushing's disease.

This report describes a patient with pituitary-dependent Cushing's disease who had a preoperative ACTH gradient to the left at the level of the cavernous sinus. Intraoperatively, an adenoma was found entirely within the left cavernous sinus, with no direct connection to the pituitary gland. To our knowledge, such a tumor has not been reported previously. This case has implications for the diagnosis, treatment, and follow-up of patients with pituitary-dependent Cushing's disease. The presence of an entirely extrasellar ACTH-releasing adenoma in the cavernous sinus could explain why pituitary-dependent Cushing's disease may persist postoperatively, even after total hypophysectomy. The diagnosis of an intracavernous tumor can be established by cavernous sinus venography. An extrasellar intracavernous adenoma can be diagnosed intraoperatively after careful negative exploration of the sellar contents followed by incision of the cavernous sinus on the side of the ACTH gradient established by venous sampling.

Adenoma↗
PubMed1995

Pediatric pituitary adenomas.

Previous series of pediatric pituitary adenomas have been small and have not been analyzed by age group. We analyzed the frequency, manifestation, course, and biology of these tumors before, during, and after puberty in 136 children younger than 20 years old at surgery, identified by review of 2230 patients treated from 1969 to 1993. Tumors were classified by clinical phenotype. Adrenocorticotropic hormone-releasing adenomas were most common before puberty, and prolactinomas were most common during and after. The frequencies of adrenocorticotropic hormone-releasing adenomas, prolactinomas, and endocrine-inactive adenomas differed from those in adults. Growth arrest was common with all types except growth hormone (GH)-releasing adenomas; menstrual irregularities were common with all but adenomas causing Nelson syndrome. Among girls with prolactinomas, the preoperative duration of primary amenorrhea was longer than that of other symptoms. Tumor size differed by adenoma type. Serum hormone levels shortly after surgery correlated with the recurrence of prolactinomas and GH-releasing adenomas. The prolactinoma size correlated with the maximum preoperative serum prolactin level; boys had larger tumors and higher preoperative and postoperative prolactin levels. We conclude that pediatric pituitary adenomas vary in size, age at symptom onset, and frequency before, during, and after puberty. Most adenomas can cause menstrual irregularities, and primary amenorrhea should prompt investigation of the sella. Growth arrest is common with all adenomas except GH-releasing adenomas. Serum prolactin and GH levels measured at 1 to 5 days after surgery indicate the risk of recurrence of prolactinomas and GH-releasing adenomas, respectively.

Adenoma↗
PubMed1995

Delayed onset of hyponatremia after transsphenoidal surgery for pituitary adenomas.

Hyponatremia is rarely reported as a delayed complication of transsphenoidal resection of pituitary adenoma. Usually attributed to the syndrome of inappropriate secretion of antidiuretic hormone (SIADH), hyponatremia causes nonspecific symptoms, often after hospital discharge. To clarify the frequency, presentation, and outcome of this poorly understood complication, we reviewed our database of 2297 patients who underwent transsphenoidal pituitary surgery between February 1971 and June 1993. Of 53 patients (2.3%) treated for symptomatic hyponatremia, 11 were excluded (2 received arginine vasopressin within 24 hours, 1 had untreated hypothyroidism, 4 had untreated adrenal insufficiency, and 4 had incomplete records). The remaining 42 patients (1.8%), 11 men and 31 women aged 21 to 79 years, presented 4 to 13 days (mean, 8 d) postoperatively with nausea and vomiting (20 patients), headache (18 patients), malaise (12 patients), dizziness (4 patients), anorexia (2 patients), and seizures (1 patient). Hyponatremia was unrelated to sex, age, adenoma type, tumor size, or glucocorticoid tapering. Although the clinical picture in our patients is consistent with SIADH, this was not supported by the antidiuretic hormone levels, which were normal or low-normal in the two patients in whom they were measured, suggesting the possibility that low serum sodium may not reflect SIADH. In all patients, hyponatremia resolved within 6 days (mean, 2 d); treatment consisted of salt replacement and mild fluid restriction in 37 patients and fluid restriction only in 4 (treatment unknown in 1). Delayed hyponatremia after transsphenoidal resection of pituitary adenoma is not as rare as previously thought, nor is it necessarily associated with SIADH or with hypoadrenalism during glucocorticoid tapering.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenoma↗
PubMed1995

Identification of the alpha 3 chain of type IV collagen as the common autoantigen in antibasement membrane disease and Goodpasture syndrome.

Antiglomerular basement membrane (GBM) antibodies can cause glomerulonephritis or pulmonary hemorrhage by themselves or Goodpasture syndrome when they occur together. It is unknown if variations in antibody reactivity contribute to the different patterns of organ involvement seen in this disease. This study examines the reactivity of the alpha 1-alpha 6 NC1 domains of Type IV collagen, the putative autoantigen, in sera from patients with anti-GBM antibodies after various clinical presentations of lung hemorrhage and renal injury. Serum or plasma containing anti-GBM antibodies from 35 patients with combined glomerulonephritis and pulmonary hemorrhage, 19 with glomerulonephritis alone, and 4 with pulmonary hemorrhage alone were compared with samples from 19 normal controls and 32 patients with other kidney diseases. Four different immunologic assays were performed with bovine alpha 1-alpha 6(IV) and recombinant human type alpha 1-alpha 5(IV) collagen NC1 domains. The study found that the anti-GBM antibodies from all patients reacted with the alpha 3(IV) NC1 (85% exclusively). Additional limited reactivity with the alpha 1(IV) NC1 and alpha 4(IV) NC1 was found in 15 and 3%, respectively. This non-alpha 3(IV) NC1 reactivity was most frequent in the patients with anti-GBM antibodies and glomerulonephritis alone. None of the patients had reactivity to other basement membrane components like laminin, fibronectin, heparan sulfate proteoglycan, entactin, or the 7S and triple helical fragments of Type IV collagen. The observed alpha-chain NC1 reactivity was confined to patients with anti-GBM antibodies with no additional reactivities detected among a large number of other kidney diseases controls. The correlation of alpha 1-alpha 6(IV) NC1 reactivity in a large number of patients with anti-GBM antibodies defined by classic assays definitively establishes that reactivity to alpha 3(IV) NC1 domains is both sufficient and necessary for the expression of autoimmune disease directed to the NC1 domain of Type IV collagen. On the basis of the evidence, the classification of antibasement membrane disease and Goodpasture syndrome as anti-Type IV collagen disease is proposed.

Animals↗
PubMed1995

Expression and localization of inducible nitric oxide synthase in anti-Thy-1 glomerulonephritis.

To elucidate a possible involvement of nitric oxide in the development of a mesangial proliferative glomerulonephritis induced by anti-Thy-1 antibody administration, glomerular expression of three isoforms of NO synthase (NOS), inducible NOS (iNOS), brain NOS, and endothelial NOS, was examined at both mRNA and protein levels by ribonuclease protection assay and immunofluorescence microscopy. Light microscopy showed an accumulation of polymorphonuclear leukocytes at 1 hour, lysis of mesangial cells at 1 day, a mesangial proliferative lesion at 4 to 10 days, and minimal residual glomerular lesions by 28 days. Ribonuclease protection assay showed that the glomerular expression of iNOS mRNA peaked at 1 hour and decreased thereafter. No substantial expression of iNOS mRNA was observed in normal glomeruli or in the nephritic glomeruli obtained at different time points (1, 4, 10, or 28 days). By immunofluorescence microscopy with a specific monoclonal antibody, an intense reaction for iNOS was demonstrated in a few cells in the glomeruli at 1 hour. Most of the iNOS-positive cells were identified as polymorphonuclear leukocytes. iNOS-positive cells were found less frequently in the glomeruli on days 1 and 4. Endothelial NOS mRNA was constitutively expressed in normal glomeruli and increased biphasically with two peaks at 1 hour and at 4 days or later; however, the peak expression was much less than that of iNOS mRNA at 1 hour. Expression of brain NOS mRNA was not detectable in either normal or nephritic glomeruli. These results show that iNOS is predominantly expressed in polymorphonuclear leukocytes accumulating at 1 hour in the glomeruli of anti-Thy-1 glomerulonephritis and suggest an involvement of NO in the initiation of the disease.

Animals↗
PubMed1995

Selective type IV collagen defects in the urothelial basement membrane in interstitial cystitis.

PURPOSE: The study sought to identify changes in the urothelial basement membrane (UBM) associated with interstitial cystitis (IC). MATERIALS AND METHODS: Immunohistochemical assessment of bladder biopsies from IC patients and controls was compared with clinical and histologic findings. RESULTS: Selective decreases or loss of type IV collagen staining, but not laminin, were found in the UBM of 5 of 11 IC patients with no change in type IV collagen staining of other bladder wall sites. CONCLUSIONS: The loss of type IV collagen may represent a primary or secondary event and could alter the UBM's role in permeability, thereby contributing to the pathogenesis of IC in the subset of IC patients exhibiting this change.

Adult↗
PubMed1995

Pituitary tumors. Current concepts in diagnosis and management.

Diagnostic advances have resulted in earlier and more frequent recognition of pituitary tumors. Pituitary tumors cause problems owing to the hormones they secrete or the effects of an expanding sellar mass--hypopituitarism, visual field abnormalities, and neurologic deficits. Prolactin-secreting tumors (prolactinomas), which cause amenorrhea, galactorrhea, and hypogonadism, constitute the most common type of primary pituitary tumors, followed by growth hormone-secreting tumors, which cause acromegaly, and corticotropin-secreting tumors, which cause Cushing's syndrome. Hypersecretion of thyroid-stimulating hormone, the gonadotrophins, or alpha-subunits is unusual. Nonfunctional tumors currently represent only 10% of all clinically diagnosed pituitary adenomas, and some of these are alpha-subunit-secreting adenomas. Insights into the pathogenesis and biologic behavior of these usually benign tumors have been gained from genetic studies. We review some of the recent advances and salient features of the diagnosis and management of pituitary tumors, including biochemical and radiologic diagnosis, transsphenoidal surgery, radiation therapy, and medical therapy. Each type of lesion requires a comprehensive but individualized treatment approach, and regardless of the mode of therapy, careful follow-up is essential.

Adenoma↗
PubMed1995

Surgery for low-grade glioma: rationale for early intervention.

We feel that early surgical intervention is appropriate in the patient who presents with a clinical picture suggesting a low-grade glioma. Neuroimaging is not adequate to make an accurate diagnosis of the underlying pathology. Tumor tissue sampling allows a more specific diagnosis and testing for biologic factors such as the proliferative potential of the lesion. Surgical diagnosis allows a disease-specific therapy to be more appropriately prescribed to the patient, including the option for no further treatment, radiotherapy, and/or chemotherapy. There is compelling early data that suggest that the extent of surgery and the postoperative tumor volume will be predictive of outcome in at least some tumor types. We encourage participation of physician and patients in well-designed clinical trails that will ultimately answer the many questions that remain about these unique diseases.

Brain Neoplasms↗
PubMed1994

Differentiation of the T helper phenotypes by analysis of the methylation state of the IFN-gamma gene.

Th1 and Th2 CD4+ T cell clones have been defined by their ability to produce different lymphokines. However, the processes by which CD4+ T cells differentially regulate lymphokine gene expression have not been well defined. In this report, we demonstrate that the methylation status of a CpG dinucleotide contained within a TATA proximal regulatory element of the IFN-gamma promoter correlates with the transcription of the gene. In murine Th1 clones and two human CD4+ Th0 clones, this site is either completely or partially hypomethylated, whereas in murine Th2 clones this site is > 98% methylated. Treatment of murine Th2 clones with 5-azacytidine, an agent that inhibits methylation of the DNA, converts these cells to IFN-gamma producers. Additional targets for methylation outside the transcriptional control regions of the IFN-gamma genetic locus were found to be hypomethylated in Th2 cells but not in Th1 cells. Electrophoretic mobility shift assays (EMSA) revealed at least five distinct protein-DNA complexes that are formed with an oligonucleotide containing the IFN-gamma promoter TATA proximal regulatory element, and in vitro methylation of this site results in a loss of these three complexes. Furthermore, a comparison of nuclear extracts prepared from Th1 and Th2 clones revealed that the EMSA patterns were qualitatively similar but differed quantitatively. In addition, transient transfection of a murine IFN-gamma promoter-chloramphenicol acetyl transferase (CAT) gene construct into both Th1 and Th2 clones produced CAT activity that was not inducible by anti-CD3, indicating that hypomethylation per se of the promoter alone is not sufficient for inducible gene expression.

Animals↗
PubMed1994

Correlation between the bromodeoxyuridine labeling index and the MIB-1 and Ki-67 proliferating cell indices in cerebral gliomas.

BACKGROUND: Recently, it has been shown that heating paraffin embedded tumor sections in a microwave oven can reactivate an epitope of Ki-67 protein that is recognized by the monoclonal antibody MIB-1. With this technique, a close correlation was shown between the bromodeoxyuridine labeling index (BUdR LI) and the MIB-1 proliferating cell index (PCI) in corresponding regions of glioblastomas. METHODS: The reliability of the MIB-1 PCI as a marker of proliferation was evaluated in 90 cerebral gliomas. The MIB-1 immunostaining of ethanol-fixed, paraffin embedded sections of 23 moderately anaplastic astrocytomas, 22 highly anaplastic astrocytomas, 30 glioblastomas, and 15 mixed malignant gliomas was compared with the BUdR LI and, in some cases, the Ki-67 PCI. RESULTS: MIB-1 positive cells were detected easily in the majority of the cases, and the MIB-1 immunostaining was often superior to that of Ki-67 in individual tumors. The MIB-1 PCI was significantly higher than the Ki-67 PCI and the BUdR LI. Linear-regression analysis showed significant correlations among the three indices. The MIB-1 PCI was correlated with the BUdR LI in each group of the astrocytic tumors and mixed malignant gliomas; the MIB-1 PCI was approximately 2.4-2.8 times higher than the BUdR LI. CONCLUSIONS: The close correlation between the MIB-1 PCI and the in vivo BUdR LI in serial sections of glioma subtypes suggests that MIB-1 immunostaining is a useful technique for analyzing the proliferative potential of individual gliomas.

Adult↗
PubMed1994

Alternative splicing of the NC1 domain of the human alpha 3(IV) collagen gene. Differential expression of mRNA transcripts that predict three protein variants with distinct carboxyl regions.

Three clones of NC1 of alpha 3(IV) collagen, named Q1, L5, and V, were isolated from human kidney; these predict three variant alpha 3(IV) NC1 domains of 232-, 60-, and 199-amino acid residues, respectively, with unique COOH-termini. The human collagen IV gene (COL4A3) was isolated and characterized, and it was shown that the cDNA variants arose from alternative splicing by deletion of exon 4 in L5 and deletion of exon 2 in V. The mRNA transcripts were differentially expressed in fetal and adult human kidney with Q1 the major species. Exon 4-L5 lacked 183 residues from the carboxyl terminus with a frameshift producing a unique 11-amino acid terminal peptide. In exon 2-V a frameshift resulted in a unique V carboxyl terminus of 53 novel peptides with a new glycosylation site. The size of recombinant proteins indicated the frameshifts and new stop codons were as predicted. The multiple forms of the alpha 3(IV) NC1 region may contribute to autoimmune glomerular disease and hereditary nephritis, in which this portion of the collagen IV molecule is thought to play an important role.

Adult↗
PubMed1994

Lipopolysaccharide-induced cytokine production in human monocytes: role of tyrosine phosphorylation in transmembrane signal transduction.

The signal transduction events that follow the binding of lipopolysaccharide (LPS) to the macrophage cell surface are not well defined. In the current studies LPS was found to induce alterations in phosphorylation of monocyte proteins on tyrosine. Herbimycin A and genistein, inhibitors of tyrosine kinases, markedly attenuated LPS-induced tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) protein and mRNA production. Reciprocally, the tyrosine phosphatase inhibitor sodium orthovanadate enhanced LPS-induced production of TNF-alpha. LPS induced a concentration-dependent increase in tyrosine phosphorylation of several proteins, which paralleled and preceded the onset of LPS-induced TNF-alpha production. LPS stimulation had different but reproducible effects on three members of the src family of tyrosine kinases. Both Hck and Lyn kinase activity increased before the onset of TNF-alpha production, consistent with their participation in the observed LPS-induced tyrosine phosphoprotein accumulation. In contrast, Yes kinase activity was not affected. These observations were made at concentrations of LPS that required serum rich in LPS-binding protein and the monocyte surface antigen CD14 for TNF-alpha production. These data indicate that tyrosine kinases and phosphatases are involved in the signal transduction cascade by which LPS induces production of TNF-alpha and IL-6 by human monocytes, and suggest that Lyn and Hck are candidate participants in this process.

Acute-Phase Proteins↗
PubMed1994

Regional differences in bromodeoxyuridine uptake, expression of Ki-67 protein, and nucleolar organizer region counts in glioblastoma multiforme.

To investigate intratumoral differences in indices of tumor cell proliferation, we measured the bromodeoxyuridine labeling index (BrdUrd LI), the Ki-67 protein proliferating cell indices (PCIs) determined by monoclonal antibody MIB 1 in microwave-processed paraffin sections (MIB 1 PCI) and in some cases by monoclonal antibody in frozen sections (Ki-67 PCI), and counts of argyrophilic nucleolar organizer regions (AgNORs) in 20 glioblastomas. In the most actively proliferating areas, MIB 1 and Ki-67 PCIs correlated well with the BrdUrd LI and with each other, while AgNOR counts correlated less strongly with these indices. In less active areas, the MIB 1 PCI and BrdUrd LI changed concomitantly from one area to another within a tumor except in areas of pseudopalisading with necrosis; in these areas the BrdUrd LI decreased significantly compared with neighboring tumor tissue, while the MIB 1 PCI did not. There was very little staining of gemistocytic nuclei with either anti-BrdUrd or MIB 1 monoclonal antibodies; this supports the concept that gemistocytes are mainly quiescent cells. AgNORs in all of the above-mentioned areas varied from tumor to tumor, which suggests that they may indicate some cellular activity other than proliferation. The close correlation between the BrdUrd LI and Ki-67 protein PCIs in corresponding regions of glioblastomas suggests that MIB 1 staining of microwave-processed paraffin sections can be used to evaluate the growth potential of individual glioblastomas and possibly of other gliomas as well.

Adult↗
PubMed1994

Proliferative potential and prognostic evaluation of low-grade astrocytomas.

Despite their histological similarity, low-grade astrocytomas vary widely in their clinical behavior. To elucidate this variable behavior, we measured the proliferative potential of 69 primary and 18 recurrent low-grade astrocytomas and correlated the results with the clinical characteristics and outcome. Each patient received an intravenous infusion of bromodeoxyuridine (BUdR); BUdR-labeled nuclei in excised tumor specimens were identified by immunoperoxidase staining. The BUdR labeling index (LI), or S-phase fraction, ranged from < 1 to 9.3%; the LI was < 1% in 64 (74%) patients and > or = 1% in 23 patients (26%). The LI did not appear to be associated with age, sex, tumor location, or whether the tumor was primary or recurrent. A Cox proportional-hazards analysis of the influence of the LI and other variables (age, sex, tumor location, extent of surgery, primary versus recurrent tumor) on survival showed that the LI and extent of surgery (total resection, subtotal resection, biopsy) were significant in predicting both survival and progression-free survival for all patients and for patients with primary tumors. The LI was also significant in predicting progression-free survival for patients with recurrent tumors. The correlation between the BUdR LI and both survival and time to recurrence suggests that the outcome of low-grade astrocytomas varies according to the proliferative potential. The growth rate of these histologically similar tumors should be assessed individually in order to select specific treatment.

Adolescent↗
PubMed1994

Extracellular matrix accumulation in immune-mediated tubulointerstitial injury.

The accumulation of excessive extracellular matrix (ECM) following tubular injury likely represents an imbalance between ECM production and degradation. We assessed the temporal relationship between the accumulation of ECM, cell adhesion molecules, matrix degrading proteinases, and their inhibitors in a rat model of anti-tubular basement membrane (TBM) antibody-associated tubulointerstitial nephritis (TIN) by the RNase protection assay and immunohistochemistry. There was an increase in the steady state expression of fibronectin (FN) and alpha 2(IV) collagen mRNAs beginning on day 7 with the onset of neutrophil infiltration. An increase in alpha 1(III) collagen and alpha 1-integrin did not occur until days 9 and 10, respectively, at which time mononuclear leukocytes were the predominant infiltrating cell. Increased levels of FN, alpha 1(III), alpha 2(IV) and alpha 1-integrin mRNAs occurred through day 14. By immunohistochemistry, increased accumulation of collagen IV, heparan sulfate proteoglycan, and laminin were detected along the thicken TBM; collagens I and III were immunolocalized within the tubulo-interstitium, while FN was present in both the TBM and interstitium in rats with TIN on day 14. The increase in matrix accumulation was associated with little or no increase in proteinases. u-PA transcripts fell beginning on day 8, with recovery to control values by day 12. Transin mRNA was found at low levels only on days 8 and 9, and the protein could not be detected by Western blotting. In contrast, these changes were associated with an increase in proteinase inhibitors, so that TIMP and PAI-1 mRNAs increased beginning on day 7 and persisted through day 14.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗