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Biomedical subjects

C B Wilson

Publications and source records attributed to C B Wilson.

At least 289 records · Page 16Linked to original sources

Intrachiasmatic craniopharyngioma: a rare cause of chiasmal thickening. Case report.

The authors describe the case of a young man who presented with a central scotoma in one eye and a temporal hemianopsia in the other. Magnetic resonance imaging showed distinctive bilobed thickening of the chiasm and a "potbelly" expansion of the contiguous optic nerves. The distal portions of the intracranial optic nerves appeared normal. At craniotomy, incision of the lamina terminalis exposed intraventricular craniopharyngioma with anterior extension into the chiasm and proximal optic nerves. Partial resection of the tumor restored normal vision.

Adult↗

Treatment of medulloblastoma with procarbazine, hydroxyurea, and reduced radiation doses to whole brain and spine.

Forty-seven patients with medulloblastoma were treated postoperatively with procarbazine, followed by craniospinal radiation therapy in combination with hydroxyurea. The radiation dose to the posterior fossa was 55 Gy; the spinal cord received 25 Gy and the whole brain 25 to 35 Gy (mean 33 Gy). Seventeen tumors recurred. Only one initial recurrence was in the spinal subarachnoid space; 10 (59%) were in the posterior fossa, and four (24%) were supratentorial. The estimated 5-year disease-free survival probability was 55%; the 5-year overall survival rate was 66%. Myelotoxicity occurred in 38% of patients, but in only one case was it severe enough to warrant reducing the total dose of radiation. It was concluded that good-risk medulloblastoma patients may be treated with radiation dosages as low as 25 Gy to the spinal axis and to the whole brain without increasing the risk of recurrence outside the posterior fossa. Chemotherapy with procarbazine followed by radiation therapy and hydroxyurea during radiation therapy was well tolerated and may play a role in reducing radiation dosages outside the posterior fossa.

Adolescent↗

Pineal region tumors in children.

The authors believe that the preferred treatment for pineal region tumors in children requires definitive surgery with a histological diagnosis and that a conservative approach consisting of shunting and radiation therapy no longer seems to be appropriate. The results are reported of a retrospective review of the presentation, treatment, and outcome of 36 children under the age of 18 years treated between 1974 and 1986. Eleven children had germinomas (two-cell type), seven had astrocytomas, and the remaining 18 had 15 histologically different tumor types. Surgery was performed on 30 patients; there were no deaths, but a 10% rate of persistent morbidity was found. The median follow-up period was 4 years. Nine (82%) of 11 patients with germinomas are alive without evidence of recurrence; one child died from recurrent tumor in the pineal region and another is presently being treated for recurrent tumor of the spinal cord. Six (86%) of the seven patients with astrocytoma are well after biopsy and radiation therapy. Of the remaining 18 children, five (28%) died from tumor progression. The cerebrospinal fluid (CSF) tumor markers alpha-fetoprotein and beta-human chorionic gonadotropin were helpful in determining the presence of malignant germ-cell tumors, particularly those with a poor prognosis. Magnetic resonance imaging was useful for diagnosis and for planning the operative approach. Magnetic resonance images showed the presence of pineal region tumors in four children with hydrocephalus who had no evidence of tumor on computerized tomography scans. Because the great variety of tumor types found in the pineal region must be treated in different ways and because improved microsurgical and stereotaxic surgical techniques have made mortality and morbidity rates acceptably low, a biopsy diagnosis should be obtained in all patients. Preoperative assessment of CSF tumor markers and cytology is useful for the identification of patients who have a poor prognosis.

Adolescent↗

Primary cerebral angiosarcoma. Case report.

A 65-year-old man with a history of exposure to industrial solvents developed a primary cerebral angiosarcoma in the left posterior parieto-occipital lobe. The tumor had features typical of angiosarcoma on light and electron microscopy, immunohistochemical evidence of factor VIII-related antigen produced in tumor cells, and a high labeling index with bromodeoxyuridine. The relationship of angiosarcoma to toxins and viruses is discussed.

Aged↗

Results of transsphenoidal microsurgery for growth hormone-secreting pituitary adenoma in a series of 214 patients.

Of 214 patients with acromegaly who underwent transsphenoidal microsurgical resection of a pituitary adenoma, 54% had growth hormone (GH) levels below 5 ng/ml and 74% had levels less than 10 ng/ml immediately after surgery. Among the 174 patients who could be contacted for long-term follow-up review (average duration 76 months), most recent GH determinations were available for 165. Of these 165 patients, 131 (79.4%) have a GH level less than 5 ng/ml and 153 (92.7%) have a level below 10 ng/ml; these represent 75.3% and 87.9%, respectively, of the total 174 patients reviewed. Fifty-two patients received postoperative radiation therapy. Nine patients underwent reoperation. There were five cases of tumor recurrence following an apparent surgical cure (4.3%), nine new instances of anterior pituitary hypofunction (5%), and five failures of multimodality therapy (2.3%). There were no perioperative deaths, five cases of cerebrospinal fluid leak requiring surgical repair (2.2%), and four cases of postoperative meningitis (1.8%). Permanent diabetes insipidus did not occur. Two of 52 patients who were irradiated postoperatively had severe complications; 23 (54.8%) of 42 patients who were available for follow-up evaluation had developed panhypopituitarism; and eight (19%) of 42 had normal pituitary function an average of 44 months postirradiation.

Acromegaly↗

Suprasellar meningiomas: the effect of tumor location on postoperative visual outcome.

The authors reviewed 38 cases of suprasellar meningioma to determine the correlation between tumor site and postoperative visual outcome. Progressive visual loss, the most frequent initial complaint (94.7%), occurred over a mean of 24 1/2 months, was most often unilateral (18 patients) or bilateral but asymmetrical (14 patients), and was severe (20/200 vision or worse) in 23 patients; 24 patients had visual field abnormalities. Computerized tomography or magnetic resonance studies clearly delineated the lesions but did not appear to permit earlier diagnosis. Eleven patients had tumors limited to the tuberculum sellae; the tumor extended from the tuberculum sellae onto the planum sphenoidale in nine patients, into one optic canal in eight, onto the diaphragma sellae in seven, and onto the medial sphenoid wing in three. Patients with tumors affecting the optic canal had severe unilateral visual loss more often than those with tumors at other sites. Tumors limited to the tuberculum sellae were most often completely resected; postoperative recovery of vision was also most frequent in patients with tumors at this site. Tumors involving the diaphragma sellae or the medial sphenoid wing were least often completely removed and most likely to be associated with postoperative visual deterioration. Overall, 42% of patients had improved vision postoperatively, 30% remained unchanged, and 28% were worse. After a mean follow-up period of 38 months, 24 patients are doing well, four have significant visual disability, and three are blind or doing poorly. Two patients died of causes unrelated to their tumor. Three patients have had tumor recurrence.

Adult↗

Prognostic implications of the proliferative potential of low-grade astrocytomas.

The proliferative potential of low-grade astrocytomas was estimated in 47 patients. Each patient received an intravenous infusion of bromodeoxyuridine (BUdR), 150 to 200 mg/sq m, at the time of craniotomy to label cells in deoxyribonucleic acid (DNA) synthesis; the percentage of S-phase cells, or BUdR labeling index (LI), of each tumor was determined immunohistochemically. In 29 patients (60%), the tumors had BUdR LI's of less than 1%, indicating a slow growth rate; only three (10%) of these patients died of recurrent tumor during a follow-up period of up to 3 1/2 years. In contrast, of the 18 patients (40%) whose tumors had BUdR LI's of 1% or more, 12 (67%) had a recurrence and nine died during the same follow-up period. These results show that the proliferative potential, as reflected by the BUdR LI, is an important prognostic factor that separates low-grade astrocytomas into two groups and provides a more scientific rationale for selecting treatment for individual patients.

Astrocytoma↗

An evaluation of the role of complement depletion in experimental membranous nephropathy in the rat.

Passive Heymann nephritis (PHN), a model of experimental membranous nephropathy produced by the administration of anti-Fx1A antibody, was studied by micropuncture measurement of glomerular hemodynamics and by assessment of immunologic and morphologic findings. The effect of complement depletion on these parameters was evaluated by administering cobra venom factor. Five days after administration of anti-Fx1A Ab to PHN controls, abnormal proteinuria developed and nephron filtration rate decreased due to modest reductions in nephron plasma flow and major reductions (75%) in the glomerular ultrafiltration coefficient. Glomerular capillary hydrostatic pressure gradient was significantly increased and decreased tubular reabsorption was also evident. Complement depletion prevented abnormal proteinuria and normalized tubular reabsorption and some of the glomerular hemodynamic parameters (nephron plasma flow and glomerular capillary hydrostatic pressure gradient). Values for the glomerular ultrafiltration coefficient, a possible index of membrane damage, were significantly improved (100%) after cobra venom factor treatment, although they remained below normal values. Only minimal differences in glomerular and epithelial cell morphology and appearance of electron-dense material were noted between PHN and PHN + cobra venom factor. These data suggest therefore that both complement-dependent and independent mechanisms contribute to explain the changes in nephron filtration and reabsorption that occur in this model of experimental membranous nephropathy.

Animals↗

A new method for reduction of endotoxin contamination from protein solutions.

A method of reducing endotoxin contamination in protein-containing solutions is described here using a combination of polymyxin B-Sepharose 4B (PB-Seph 4B) affinity binding and endotoxin-protein dissociation with the dialyzable surfactant, octyl-beta-D-glucopyranoside (OBDG). Using the limulus amoebocyte lysate (LAL) assay to detect endotoxin, greater than 1000-fold reduction of endotoxin reactivity could be accomplished from a contaminated commercial preparation of bovine catalase. Importantly, this occurred with only a 24% protein loss and an 11% loss of catalase enzymatic activity after treatment. The treated catalase appeared to be largely endotoxin-free since it no longer elicited a pyrogenic response in rabbits or primed for intravascular coagulation of the generalized Shwartzman reaction. Of interest, OBDG treatment of Salmonella minnesota Re595 lipopolysaccharide enhanced its ability to bind to serum high density lipoproteins which might contribute to decreased in vivo toxicity. In quantitative studies using radiolabeled endotoxin, the OBDG was shown to be capable of dissociating protein-bound endotoxin thereby facilitating its binding to the PB-Seph 4B adduct. The technique was also useful in removing radiolabeled endotoxin added to human IgG. The methodology described here would be expected to have general usefulness in reducing endotoxin contamination of macromolecular solutions that can bind and retain endotoxin.

Catalase↗

Complement dependence of antibody-induced mesangial cell injury in the rat.

Intravenous administration of rabbit anti-rat thymocyte serum (ATS) reactive with Thy-1-like antigens present on rat mesangial cells induces almost immediate (1-hr) mesangial cell injury in rats followed by sequential mesangiolytic and mesangial-proliferative/infiltrative lesions. To determine the role of complement in these ATS-induced glomerular lesions, ATS was given to Lewis rats that had been depleted of C3 by cobra venom factor (CVF). CVF treatment prevented the degenerative changes in mesangial cells and accumulation of even the few polymorphonuclear leukocytes (PMN) seen in the glomeruli (2.67 PMN/glomerulus) 1 hr after ATS-treatment in rats not given CVF. In addition, CVF prevented the mesangiolysis and mesangial hypercellularity seen at day 4. Rat C3 and late complement components identified in the mesangial of ATS-treated rats in close association with the deposition of rabbit immunoglobulin G was also absent as a result of CVF treatment. CVF treatment did not affect binding of ATS to glomeruli as studied by immunofluorescence or paired label radioisotope techniques. The depletion of leukocytes and/or PMN by irradiation or treatment with anti-I-MN serum had no effect on the induction of the acute mesangial cell damage or the mesangiolytic lesion. Irradiation did diminish the 4-day proliferative/infiltrative lesion. Complement depletion normalized the ATS-induced increase in mesangial uptake of heat-aggregated human gamma-globulin (655.0 +/- 35.2 micrograms in ATS-treated vs 20.3 +/- 2.9 micrograms/5 X 10(4) glomeruli in ATS plus CVF-treated rats; mean +/- SEM). Small immune deposits present in the mesangial areas of kidneys 4 to 5 days after CVF treatment represented CVF-anti-CVF antibody-C3 complexes. The model of mesangial cell damage induced by ATS in the rat is complement-dependent and may relate, at least in part, to complement-mediated mesangial cell lysis.

Animals↗

Regulation of pp56lck during T-cell activation: functional implications for the src-like protein tyrosine kinases.

The lymphocyte-specific protein tyrosine kinase pp56lck, encoded by a member of the src gene family, is implicated in the control of T-cell growth and differentiation. Purified resting human T lymphocytes contain appreciable levels of lck mRNA and of pp56lck. Upon activation of these T cells, levels of lck mRNA and of pp56lck promptly decline. These reductions in lck mRNA and protein expression are closely correlated with the induction of lymphokine production. Both require identical stimuli and follow a similar time course of response. Down-regulation of lck expression, however, is not correlated with proliferation. Our results provide an example of regulation of a src-like protein tyrosine kinase in a normal fully differentiated cell population and suggest that modulation of lck RNA and protein expression is an important feature of the lymphocyte activation sequence leading to lymphokine production.

Adult↗

Establishment and characterization of five cell lines derived from human malignant gliomas.

We established and characterized five cell lines derived from human malignant gliomas (four glioblastomas multiforme and one highly anaplastic astrocytoma). All cell lines exhibited tumor cell morphology and growth kinetics, and anchorage-independent growth in soft agar. Cytogenetic analysis revealed significant aneuploidy in all five cases as well as clonal chromosomal alterations unique to each cell line. No cell line was tumorigenic in athymic mice. Two of the cell lines were sensitive to carmustine (BCNU) in monolayer and soft-agar cultures. Electron microscopy showed marked variability between cell lines in the number and structure of intracytoplasmic organelles; SF-126 formed collagen fibers in vitro. Immunohistochemical analysis of the surgical specimens showed variable expression of glial fibrillary acidic protein (GFAP) in malignant astrocytes; positive immunostaining for glycoproteins of the extracellular matrix was found predominantly in perivascular regions. In early-passage cultures, only cell line SF-295 expressed GFAP; at establishment, none of the cell lines expressed GFAF or glutamine synthetase. Fibronectin and laminin were expressed by all cell lines in early-passage culture, but expression of these glycoproteins at establishment was variable. Only SF-126 was positively identified by immunostains for procollagen III; this was also the only cell line in which DEAE-cellulose chromatography and SDS-PAGE demonstrated interstitial collagen synthesis. These well-characterized glioma-derived cell lines may now serve as useful tools with which to study the cell biology of gliomas. The synthesis of interstitial collagen by a glioma-derived cell line may suggest a derivation from vascular mesenchymal elements, either reactive or transformed, in the original heterogeneous malignant glioma, rather than from a glial precursor cell.

Adult↗

Inhibition of the neutrophilic infiltrate of experimental tubulointerstitial nephritis in the Brown-Norway rat by decomplementation.

Anti-tubular basement membrane (TBM) antibody-associated tubulointerstitial nephritis (TIN) in Brown-Norway rats is induced by immunization with bovine TBM antigens and adjuvants. The lesion is characterized by linear deposition of IgG and C3 along the TBM with sequential neutrophil (Days 8-9)- and mononuclear (Day 10 and after)-dominated inflammatory infiltrates. To study the complement dependence of the infiltrative process, immunized rats were decomplemented with cobra venom factor (CVF). The CVF treatment did not affect the production or renal deposition of anti-TBM antibodies. CVF markedly reduced the neutrophilic inflammatory infiltrate. In rats immunized with suboptimal doses of soluble bovine TBM antigens to produce a mild lesion, decomplementation also decreased the mononuclear inflammatory infiltrates on Days 10-13. In rats immunized optimally with particulate TBM to induce maximally severe TIN, decomplementation did not affect the mild mononuclear cell infiltrate on Days 8 and 9 but did somewhat reduce the subsequent mononuclear infiltrate on Days 10 and 12. These results demonstrate that the anti-TBM antibody- and C3-associated neutrophilic inflammatory infiltrate is largely complement dependent. The early mononuclear cell infiltrate that was unmodified by CVF treatment may be dependent on complement-independent humoral events or related to cell-mediated immune events. A portion of the later mononuclear inflammatory infiltrate could be dependent on the preceding neutrophilic inflammatory phase.

Animals↗

Contralateral intracerebral hemorrhage as a complication of tumor biopsy.

The authors report two cases of contralateral intratumoral hemorrhage after tumor biopsy in patients with bilateral glioblastoma multiforme. There was no evidence of systemic hypertension during either procedure. The occurrence of hemorrhage distant to the site of biopsy may be related to some aspect of the surgical procedure and should be recognized as a possible complication of brain tumor biopsy procedures.

Aged↗

Use of monoclonal antibodies for diagnosis and treatment of liver tumours.

Antibody-guided diagnosis can provide information regarding malignant disease which is not obtainable by conventional techniques and in some instances this approach can help to achieve prolonged tumour-free survival. Nevertheless, there are many technology improvements that need to be made if this method is to be widely applied for routine diagnosis and therapy. Already, encouraging therapeutic responses have been reported using 131I-labelled polyclonal and monoclonal antibodies in the treatment of primary and metastatic liver tumours. It is essential, however, to improve the radiolabelling of monoclonal antibodies for therapeutic use. It would be more convenient and effective to use radioactive isotopes which are pure beta emitters, e.g. 90Y and 32P which would allow for outpatient therapy. It is essential to evaluate the use of multiple antibodies or antibodies that bind to multiple antigenic targets within tumours to improve dose rate and total dose amplification. Finally, encouraging clinical pilot studies should be followed up by documented randomized clinical trials in order to define properly the clinical place of monoclonal antibodies, in both the diagnosis and the therapy of malignant disease, including primary and metastatic liver tumours.

Antibodies, Monoclonal↗