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C B Wilson

Publications and source records attributed to C B Wilson.

At least 163 records · Page 9Linked to original sources
PubMed1993

A new method for analyzing the cell kinetics of human brain tumors by double labeling with bromodeoxyuridine in situ and with iododeoxyuridine in vitro.

BACKGROUND: Cell kinetics studies performed with immunohistochemical techniques to estimate the S-phase fraction have elucidated the proliferative potential of individual brain tumors. METHODS: The authors developed a new double-labeling method that enables other cell kinetics variables, including the duration of the S-phase (Ts) and the potential doubling time (Tp), to be measured from a single biopsy specimen. Using this method, 100 brain tumors were labeled with bromodeoxyuridine (BUdR) in situ and with iododeoxyuridine in vitro; labeled cells were identified by double staining with immunogold-silver and alkaline phosphatase techniques. RESULTS: Ts was fairly uniform (mean, 9.2 +/- 2.1 hour [+/- standard deviation]); range, 6.0-13.7 hours), but Tp varied from 1 day to more than 2 months. The Tp values correlated closely with the BUdR labeling index (LI), or S-phase fraction, and can be calculated from the equation: Tp = 26.9/LI1.02 (r = 0.98, P < 0.005). CONCLUSIONS: This new method facilitates the quantitation of the proliferative potential of individual brain tumors. The S-phase fraction, Ts, and Tp can be calculated from analysis of a single biopsy specimen. This method can be used to estimate the prognosis of individual patients with brain tumors and to select treatment modalities more directly than is possible with single-labeling studies with BUdR.

Biopsy↗
PubMed1993

Molecular cloning of rat cytokine synthesis inhibitory factor (IL-10) cDNA and expression in spleen and macrophages.

Rat cytokine synthesis inhibitory factor (IL-10) was cloned. Like mouse and human IL-10 (mIL-10, hIL-10), rat IL-10 exhibits strong DNA and amino acid sequence homology to the open reading frame in the Epstein-Barr virus, BCRFI. The supernatant of COS-7 transfectants with rat IL-10 was found to inhibit the production of IFN-gamma by murine Th1 cells. A probe from the rat IL-10 was used in an RNase protection assay to demonstrate that IL-10 was expressed in LPS-stimulated rat spleen and FACS-purified OX-42-reactive peritoneal macrophages. The production of IL-10 by macrophages, as shown in the current study, suggests that IL-10 may have an autocrine function in inflammation.

Amino Acid Sequence↗
PubMed1993

Prognostic significance of the proliferative potential of intracranial gliomas measured by bromodeoxyuridine labeling.

The growth potential of 174 intracranial gliomas was estimated by calculating the bromodeoxyuridine labeling index (BUdR LI). Each patient received a 30-min infusion of BUdR, 200 mg/m2, before tumor removal. Excised tumor specimens were stained immunohistochemically to determine the BUdR LI, or percentage of S-phase cells. A Cox proportional-hazards stepwise model was used to determine the correlation between the BUdR LI and survival. Among patients with glioblastomas, the BUdR LI did not improve the prediction once age was entered in the model. Among patients with malignant or low-grade astrocytomas, the BUdR LI was the best single predictor of survival. The relative predictive abilities of BUdR LI and histopathology were determined by analyzing malignant astrocytoma and glioblastomas together. Distinguishing between malignant astrocytomas and glioblastomas did not significantly improve the prediction of survival once the BUdR LI and age were entered into the model. Equations derived from the model indicate that the probability of survival is a function of age and BUdR LI in patients with glioblastoma or malignant astrocytoma, but is a function of BUdR LI alone in patients with low-grade astrocytoma. The equations also show a substantial difference in the impact of increased BUdR LI on survival among patients with glioblastoma or malignant astrocytoma and those with low-grade astrocytoma. Without highly effective treatments for specific tumor phenotypes, the survival of a patient with an intracranial glioma appears to depend strongly on the proliferative potential of the tumor. Thus, accurate estimates of the proliferative potential are important in predicting the survival of individual patients with gliomas as well as in evaluating the effectiveness of various types of treatment.

Age Factors↗
PubMed1993

Proliferative potential of brain tumors. Analyses with Ki-67 and anti-DNA polymerase alpha monoclonal antibodies, bromodeoxyuridine labeling, and nuclear organizer region counts.

Histochemical analyses with Ki-67 and anti-DNA polymerase alpha monoclonal antibodies were done, and argyrophilic nucleolar organizer regions (Ag-NOR) were counted to estimate the proliferative potential of 200 brain tumors. The findings were compared with the bromodeoxyuridine labeling index (BrdU LI), or S-phase fraction. The proliferating cell indexes (PCI), determined by Ki-67 and anti-DNA polymerase alpha monoclonal antibodies were higher and Ag-NOR more numerous in medulloblastomas, glioblastomas, and metastatic carcinomas than in astrocytomas or meningiomas. The Ki-67 and DNA polymerase alpha PCI correlated with the BrdU LI (r = 0.87 and r = 0.84, respectively) and with each other (r = 0.94). The number of Ag-NOR correlated less strongly with these indexes in some tumors. These findings suggest that Ki-67 and anti-DNA polymerase alpha monoclonal antibodies may be useful for estimating the proliferative potential of individual tumors in routine clinical practice. The number of Ag-NOR, however, does not always reflect the growth potential of each tumor.

Antibodies, Monoclonal↗
PubMed1993

Cloning two isoforms of rat cyclooxygenase: differential regulation of their expression.

Two isoforms of cyclooxygenase (COX) have been identified in eukaryotic cells: COX-1 encoded by a 2.8-kb mRNA, and a mitogen-inducible COX-2 encoded by a 4-kb mRNA. We have cloned the COX-1 and COX-2 cDNAs from the cDNA library constructed from lipopolysaccharide (LPS)-stimulated rat peritoneal macrophages. The deduced amino acid sequence showed that COX-1 contained 602 amino acids, whereas COX-2 contained 604 amino acids. There is 95% conservation of the nucleotide sequence in the open reading frame of COX-1 between the rat and the mouse, while the homology of the 3' untranslated region is 68% except for a 150 bp segment adjacent to the stop codon which is nonhomologous with the mouse. Transfection of both COX cDNAs into Cos-7 cells resulted in increased COX activity. In rat vascular smooth muscle cells, interleukin-1 beta selectively increased the expression of COX-2, but not that of COX-1, as assessed by enzyme activity, immunoprecipitation of COX proteins, and mRNA analysis. Only the brain among tissues tested exhibits basal expression of COX-2 as the major form of the enzyme. However, COX-2 mRNA was expressed in vivo in the lung and kidney, but not in the heart, after systemic administration of LPS, suggesting that COX-2 but not COX-1 plays a major role in producing COX-derived products of arachidonic acid during endotoxic shock. Thus, the two COX isoforms were differentially expressed, and COX-2 was selectively induced in response to inflammatory stimuli in rats.

Amino Acid Sequence↗
PubMed1993

Lymphokine regulation and the role of abnormal regulation in immunodeficiency.

T cell-derived lymphokines mediate or modulate various aspects of the immune response and immunodeficiency states related to abnormalities in lymphokine production or regulation are now being recognized. One example of this is seen in the fetus and neonate, in whom a physiologic immunodeficiency appears to reflect in part deficient production of certain lymphokines, including interferon-gamma, IL-4, and IL-5. The deficiency in production of these lymphokines appears to reflect to a large extent the paucity of memory T cells during these periods of life. Diminished lymphokine production has also recently been implicated as the cause for three cases of primary severe combined immunodeficiency. In disorders associated with excess IgE production, including allergy, hyper IgE syndrome, and Omenn's syndrome, excess IL-4 production relative to the production of interferon-gamma may play a contributory role. Regulation of the production of these and other T cell-derived lymphokines appears to be affected predominantly by control of lymphokine gene transcription, the basis for which is just now becoming understood at a molecular level. The elucidation of these regulatory mechanisms offers the promise for understanding the basis for disordered lymphokine production in immunodeficiency states.

Humans↗
PubMed1993

Heterogeneity of antibodies in Goodpasture syndrome reacting with type IV collagen.

Sera from patients with antiglomerular basement membrane (anti-GBM) antibodies associated with Goodpasture syndrome (GP) or glomerulonephritis were tested by ELISA and electroimmunoblot against whole basement membrane collagen (type IV) isolated from bovine anterior lens capsule (ALC) and bacterial collagenase resistant domains of the collagen molecule, that is, the NC-1 and 7-S domains isolated from either ALC or bovine and human glomerular basement membrane (GBM). Reactivity was high with the NC-1 domain by both the ELISA and the electroimmunoblot techniques. Some of the anti-GBM sera reacted with both the NC-1 and 7-S domains of both human and bovine type IV collagen. At a time when the patients' sera reacted weakly with a collagenase digest of human GBM using a radioimmunoassay, the reactivity with the NC-1 domain was also low, but some of the sera continued to react with the 7-S domain. The data suggest that there may be heterogeneity in the nature of autoantibodies with respect to collagen type IV domain reactivity in the sera of patients with anti-GBM antibody disease.

Animals↗
PubMed1993

Identification of antigenic epitopes in type IV collagen by use of synthetic peptides.

Peptides representing potential antigenic regions of the NC-1 and 7-S domains of the human alpha 1 and alpha 2, and bovine alpha 3 chains of type IV collagen were synthesized either chemically or by the recombinant DNA technique and tested by ELISA using antibodies raised in rabbits against the whole type IV collagen or the NC-1 domain. Sera from patients with Goodpasture syndrome (GP) or with acute poststreptococcal glomerulonephritis (APSGN) were also tested. The location of antigenic determinants was predicted from the primary and secondary structure of the chains, that is, aromaticity, hydrophilicity and presence of beta-turns. All synthetic peptides reacted with the antiserum to type IV collagen (anti-Col IV). Whereas all peptides arising from the NC-1 domain reacted with anti-NC-1, intact 7-S or peptides of the alpha 1 or alpha 2 chain of the 7-S domain did not react. However intact 7-S reacted with anti-Col IV. Two synthetic peptides from the NC-1 domain of alpha 1, (a.a. 71-90 and a.a. 176-190), one from the alpha 2 (a.a. 70-83) and four from the alpha 3 chain (a.a. 72-89, a.a. 104-117, a.a. 133-145, a.a. 185-203) reacted with anti-NC-1 and anti-COL IV. The above peptides, except alpha 3 (72-89) and alpha 3 (185-203), were tested and found to be reactive with sera from patients with GP.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗
PubMed1993

Associations of HLA-DR and HLA-DQ types with anti-GBM nephritis by sequence-specific oligonucleotide probe hybridization.

Twenty-three patients from the United States with anti-glomerular basement membrane nephritis (Goodpasture's syndrome) were HLA class I and class II typed by serology and HLA-DR and HLA-DQB typed using sequence-specific oligonucleotide (SSO) probes. Protocols used were those of the 11th International HLA Workshop. We were able to confirm the strong association of DR2 with the disease and, using the molecular techniques, showed that all DR2 patients were restricted to DRB1-1501 and DQB1-0602 alleles. We also found highly significant associations between disease and the alleles of DRB1-0301 and DQB1-0201. DR4 alleles as a group were not significantly more frequent among patients, but the allele DRB1-0404 did appear to be associated with the disease. The use of SSO typing provides an expanded opportunity for refined analysis of HLA and disease associated alleles.

Base Sequence↗
PubMed1993

Necessity of the spacer peptide between CA and NC in the Rous sarcoma virus gag protein.

A mutant of Rous sarcoma virus was constructed in which the nine amino acids that separate the CA and NC sequences in the Gag protein were deleted. The spacer peptide deletion mutant produced particles containing the normal complement of viral RNA and all of the viral proteins, including reverse transcriptase. Though electron microscopy revealed particles of normal morphology, the particles were noninfectious. The normally slow maturation of the CA protein, which involves cleavage of the spacer peptide from the carboxy terminus, was bypassed in this mutant, and the association between CA and the internal components of the core appears to have been disrupted. The results suggest that the spacer peptide has an essential role in directing folding and/or oligomerization of the CA subunits within the capsid structure.

Amino Acid Sequence↗
PubMed1993

Role of mesangial cell in glomerular response to volume and angiotensin II.

We have examined the physiological role of the mesangial cell in the regulation of glomerular hemodynamics utilizing mesangial cell lysis by the administration of antithymocyte antibody serum (ATS) 24 h before micropuncture evaluation. Plasma volume expansion (PVE) in normal NaCl-depleted rats increased single-nephron glomerular filtration rate (SNGFR) by 30% because of increases in single-nephron plasma flow (SNPF), whereas glomerular capillary hydrostatic pressure (PG) remained constant. SNGFR did not increase with PVE in NaCl-depleted ATS rats despite increases in SNPF, and PG increased significantly (51 +/- 2 to 67 +/- 3 mmHg) because of afferent arteriolar dilation, whereas efferent resistance remained elevated. Angiotensin II (ANG II) infusion in normal rats decreased SNGFR because of reductions in SNPF and the glomerular ultrafiltration coefficient (LpA), whereas the hydrostatic pressure gradient (delta P) increased. In ATS rats ANG II infusion did not change SNGFR, LpA, or delta P. These in vivo studies suggest that the mesangial cell plays an important role in the regulation of LpA, efferent arteriolar resistance, and the regulation of PG, whereas this cell exerts little effect on the afferent arteriole.

Angiotensin II↗
PubMed1993

LPS-induced MCP-1, IL-1 beta, and TNF-alpha mRNA expression in isolated erythrocyte-perfused rat kidney.

The capacity of the lipopolysaccharide (LPS)-stimulated isolated erythrocyte-perfused rat kidney (IEPK) to produce monocyte chemoattractant protein-1 (MCP-1), interleukin-1 beta (IL-1 beta), and tumor necrosis factor-alpha (TNF-alpha) mRNA was investigated. The IEPK was chosen to exclude the influence of circulating neutrophils and monocytes that can produce both these mediators when exposed to LPS. The control minimal LPS group (LPS < 10 pg/ml) showed a small increase in mRNA expression for MCP-1, IL-1 beta, and TNF-alpha in the cortex and medulla after 80 min of perfusion when compared with the unperfused left kidney in which no IL-1 beta or TNF-alpha mRNA and only minimal amounts of MCP-1 mRNA were detected. LPS stimulation (1 microgram/ml for 40 or 80 min) increased MCP-1, IL-1 beta, and TNF-alpha mRNA expression, which was found predominately in peritubular capillary endothelial cells by in situ hybridization. The changes were not due to a marked perturbation of LPS on renal hemodynamics. The renal vascular resistance (RVR) remained constant (40 min LPS exposure) or increased only slightly during the last 5-10 min (80 min LPS exposure) compared with a progressive increase in RVR of the minimal LPS group. The hemodynamic effects of LPS on the IEPK appear to counteract the gradual increase in RVR seen in the minimal LPS group.

Animals↗
PubMed1993

Long-term survival in patients with glioblastoma multiforme.

Few patients with glioblastoma multiforme survive more than 5 years. To identify the factors associated with long-term survival, patients with primary supratentorial glioblastoma multiforme diagnosed between 1969 and 1985 were identified from our computer data base. Twenty-two (5%) of the 449 patients identified survived at least 5 years after surgical diagnosis. There were 12 female and 10 male patients, with a mean age of 39.2 years (range, 15 to 63 yr). Twenty patients had a subtotal resection, and 2 had a gross total resection. The median duration of survival was 9.4 years. As of August 1, 1992, 10 patients were alive 5.2 to 13.6 years after diagnosis, and 1 patient was lost to follow-up after 9.4 years. Ten patients died from their tumors; 2 patients with stable tumors died, 1 from a ruptured intracranial aneurysm and 1 from erythromycin-induced hepatitis. Unusual sequelae were noted in irradiated areas in several cases. One patient had a scalp sarcoma and a basal cell carcinoma, and three patients had strokes; each of these events occurred more than 5 years after diagnosis. We conclude that among patients with glioblastoma multiforme, long-term survival is most likely for those who have a long disease-free interval after the initial diagnosis and receive multimodal therapy, including aggressive tumor removal. Other factors associated with long-term survival were younger age and high Karnofsky scores.

Adolescent↗
PubMed1993

Ceftizoxime versus vancomycin and gentamicin in neurosurgical prophylaxis: a randomized, prospective, blinded clinical study.

In a prospective, randomized, blinded study, 826 patients undergoing clean neurosurgical procedures received single intravenous doses of ceftizoxime (2 g) (n = 422) or a combination of vancomycin (1 g) and gentamicin (80 mg) (n = 404) 1 hour before an incision was made. Patients with infected or contaminated wounds and those receiving shunts or other implants were excluded. Primary wound infections occurred within 30 days in five patients in each group and were most common after spinal surgery and procedures through previous incisions. Secondary infections (pneumonias, urinary tract infections, and intravenous line-related bacteremia) occurred in 24 patients in the ceftizoxime group and 25 in the vancomycin/gentamicin group. The infection rates after transsphenoidal procedures (n = 129) were remarkably low in both groups. Ceftizoxime caused no adverse drug reactions, but six patients in the vancomycin/gentamicin group had clinically significant infusion-related hypotension or flushing. Placement of a temporary external drain, use of an operating microscope, preoperative steroids, and diabetes were not associated with increased infection rates. Analysis of routinely encountered ventricular cerebrospinal fluid and simultaneously obtained peripheral blood showed low but detectable levels of all three antibiotics within 2 hours; only ceftizoxime, however, achieved cerebrospinal fluid levels sufficient to inhibit the staphylococcus and Gram-negative bacilli most often associated with postneurosurgical infections. We conclude that ceftizoxime is as effective as vancomycin and gentamicin in neurosurgical prophylaxis but is less toxic and penetrates cerebrospinal fluid better.

Adolescent↗
PubMed1993

Dysfunction of glomerular fibrinolysis in experimental antiglomerular basement membrane antibody glomerulonephritis.

Glomerular plasminogen activator inhibitor-1 (PAI-1) steady-state mRNA and bioactivity were increased after the induction of an augmented form of antiglomerular basement membrane (GBM) antibody glomerulonephritis. PAI-1 mRNA expression was noted at 6 h, peaking at 1 day, and although falling thereafter, remained higher than that of the control group through Day 17. PAI-1 mRNA expression correlated with glomerular PAI-1 bioactivity as determined by a functional tissue type plasminogen activator (t-PA) binding assay. Glomerular PAI-1 bioactivity, not detected in controls, increased to 1.4 +/- 0.3 ng/mg of glomerular lysate at 6 h and then decreased to 0.7 +/- 0.1 ng/mg of glomerular lysate by Day 6. The mRNA of the plasminogen activators (urokinase plasminogen activator), t-PA) either remained unchanged or declined through Day 1, with a slight increase in t-PA mRNA at Day 6. Interleukin-1 beta mRNA expression was maximal at 6 h, declining by Day 3. Transforming growth factor beta 1 (TGF-beta 1) mRNA began to increase at Day 1, was maximal at Day 6, and fell only slightly by Day 17. Epidermal growth factor mRNA decreased. The increase in PAI-1 mRNA and bioactivity, possibly induced early by the interleukin-1 beta response and perhaps later by the TGF-beta 1 response, was associated with striking glomerular capillary lumen fibrin accumulations on Day 1, which decreased and appeared to recanalize as the PAI-1 mRNA and bioactivity fell. The glomerular lesion continued to have some fibrin deposits even on Day 17 and, in addition, had changes of thickened GBM, suggestive of the early stages of diffuse glomerulosclerosis. The latter had a temporal relationship with the persisting increase in TGF-beta 1 and PAI-1 mRNA levels. These observations suggest the possibility that inhibition of enzymes capable of remodeling excessive extracellular matrix production may have contributed to the thickened GBM.

Animals↗