Biomedical subjects

C B Wilson

Publications and source records attributed to C B Wilson.

At least 325 records · Page 18Linked to original sources

PubMed1986

Proliferative potential of human meningiomas of the brain. A cell kinetics study with bromodeoxyuridine.

Twenty patients with intracranial meningiomas were given a 1-hour intravenous infusion of bromodeoxyuridine (BrdU), 200 mg/m2, at the time of surgery to label tumor cells in the DNA synthesis phase (S phase). The excised tumor specimens were fixed with 70% ethanol, embedded in paraffin, sectioned, and stained by an indirect immunoperoxidase method using anti-BrdU monoclonal antibody as the first antibody. The BrdU labeling index (LI), or S-phase fraction, was determined by counting the number of BrdU-labeled cells in the tissue sections. The average LIs for nonmalignant (11 cases) and histologically malignant meningiomas (seven cases) were 0.45% and 3.9% respectively (P less than 0.05). Two hemangiopericytic variants showed average LIs of 0.53% and 4.1%. Four of seven malignant meningiomas and both hemangiopericytomas were recurrent tumors. Nine of 20 meningiomas had an LI greater than 1%, and six of those nine (67%) were recurrent. Thus, meningiomas with an LI greater than 1% appear to grow faster and recur more frequently than those with LIs less than 1%; the higher LI may indicate biological malignancy. The measurement of BrdU LI in meningioma may prove valuable in establishing the diagnosis of "malignant meningioma."

Adult↗

PubMed1986

S-phase fraction of human brain tumors in situ measured by uptake of bromodeoxyuridine.

One hundred fifty-four patients with brain tumors of various types were given an intravenous infusion of the thymidine analogue bromodeoxyuridine (BUdR), 200 mg/m2, at the time of surgery but before biopsy of the tumor to label S-phase cells. Excised tumor specimens were fixed, sectioned, and stained by immunoperoxidase methods to detect BUdR. The labelling index (LI), or percentage of BUdR-labelled cells, was calculated for each tumor specimen. The LIs of glioblastomas, medulloblastomas, and most highly anaplastic astrocytomas were 5% to 20%. The majority of moderately anaplastic astrocytomas showed LIs of less than 1%, but 30% of them had LIs similar to those of highly malignant gliomas. Most pituitary adenomas and neurinomas showed LIs of less than 1%. Nonmalignant meningiomas had LIs of less than 1%, whereas malignant meningiomas had LIs higher than 2.7%. This is an important observation, because malignant meningiomas are not well-defined histopathologically and their growth rate and rate of recurrence cannot be predicted by current diagnostic procedures. By estimating the proliferative potential of individual tumors more precisely, the BUdR LI supplements histopathological diagnosis, allowing a more accurate estimate of prognosis and facilitating the design of treatment regimens for individual patients.

Adult↗

PubMed1986

Reduced interferon-gamma mRNA levels in human neonates. Evidence for an intrinsic T cell deficiency independent of other genes involved in T cell activation.

IFN-gamma mRNA levels in human neonatal blood mononuclear cells or highly purified T cells were markedly lower than those of adult cells after incubation with Con A and PMA. In contrast, IL-2, IL-2-R, and T3 delta chain mRNA levels were kinetically and quantitatively similar in neonatal and adult T cells. The peak amount of IFN-gamma and IL-2 mRNA correlated well with IFN-gamma and IL-2 detected in supernatants of both neonatal and adult T cells. These results suggest that reduced IFN-gamma mRNA levels in neonatal T cells is due to an intrinsic deficiency at the pretranslational level and indicate that the magnitude of IL-2 and IFN-gamma gene expression can be independently modulated pretranslationally.

Genes↗

PubMed1986

Long-term culture of human corticotropin-secreting adenomas on extracellular matrix and evaluation of serum-free conditions. Secretory aspects.

Tissues from 12 human corticotropin-secreting adenomas, obtained during surgery for Cushing's disease (CD, ten cases) or Nelson's Syndrome (NS, two cases), were exclusively mechanically dispersed. Single cells and cell aggregates were plated on extracellular matrix derived from bovine corneal endothelia. Functional responses to physiological stimuli were analyzed by measuring human beta-endorphin (beta h-EP) immunoreactivity (IR) by radioimmunoassay in the culture medium. All adenomas responded with stimulated secretory activity to arginine vasopressin (AVP), corticotropin-releasing factor (CRF), or both. Cortisol higher than 10(-8) M suppressed basal secretion and CRF- or AVP-stimulated beta h-EP-IR secretion. There was no consistent difference in response of the cells when cultured in medium containing 10% fetal calf serum (FCS) or in serum-free conditions. A change of cells from serum to serum-free conditions usually resulted in 10%-50% reduction in the basal secretion level that remained stable for at least 2 weeks and, in one case (NS), 10 weeks. In cells maintained in medium supplemented with 5% serum obtained from the respective patients 40 min after adenoma removal, basal secretion was suppressed to 60% of the baseline level in a 10% FCS control. Long-term incubation with CRF (10(-9) M) showed sustained stimulation of hormone secretion. No remarkable cell proliferation was observed under basal conditions or during long-term, low-dose incubation with cholera toxin (10(-12) M) in two cases (CD), or CRF (10(-9) M) in two cases (NS, CD). Parallel beta-EP-IR and adrenocorticotropin secretion was verified in selected cases.

Adenoma↗

PubMed1986

Long-term culture of human corticotropin-secreting adenomas on extracellular matrix and evaluation of serum-free conditions. Morphological aspects.

Tissues from 12 human corticotropin-secreting adenomas, obtained during transsphenoidal surgery for Cushing's disease (CD, ten cases) or Nelson's syndrome (NS, two cases), were mechanically dispersed. The resulting single cells and cell aggregates were plated on extracellular matrix derived from bovine corneal endothelia. CD and NS cells showed distinct morphological differences initially, CD cells being much more spherical than the flattened NS cells. By 10 days at the latest after plating, however, CD and NS cells were indistinguishable morphologically. Cultured cells from both entities responded with rounding to cortisol (hydrocortisone, 10(-6) M) within 4-6 h. Synthetic ovine corticotropin-releasing factor (10(-8) M) produced flattening and extension of cytoplasmic processes after as early as 2 h.

Adenoma↗

PubMed1986

Immunologic basis for increased susceptibility of the neonate to infection.

Neonatal infection with the GBS occurs in a small fraction of exposed infants who lack specific antibody. Diminished influx of PMNs to sites of infection as a result of abnormalities in chemotaxis, bone marrow exhaustion, and to a lesser degree relative complement deficiency and decreased microbicidal activity of PMNs may be additional predisposing factors. Infection with HSV occurs more often in infants born to mothers with primary rather than secondary infection; the lack of passively acquired antibody in such infants is a possible but unproved susceptibility factor. The failure of neonates to control HSV may also be related to decreased production of or response to interferon or to decreased activity of nonimmune and immune cellular cytotoxic mechanisms. Similarly, infection with Toxoplasma and intracellular bacterial pathogens, such as Listeria, may be more severe because of the decreased generation of lymphokines and interleukins, which attract macrophages to the site of infection and enable them to kill these organisms. Much of this analysis based on in vitro and animal studies summarizes current information in a rapidly changing field rather than stating established fact. The precise age at which most of the immune functions discussed reach maturity is unknown. However, the risk of severe infection with these pathogens appears to wane by 2 to 3 months of age. Although this may partly reflect decreased exposure, we might hypothesize that immune functions that are mature by this age are those most critical for protection. Future studies focusing on changes in immune function during the first months of life may provide useful insights into the immunobiology of these diseases and direct attention to the most fruitful areas for immunologic intervention.

Adult↗

PubMed1986

A role for antiidiotypic antibodies in immunologically mediated nephritis.

In summary, evidence exists that immunologically mediated renal diseases can be modulated by interfering with the mechanism of production of autoantibodies by specific antiidiotypic immunity. However, more studies are necessary to establish efficient and safe parameters from which to suggest such treatment in human immune nephritides. Although the evidence is still circumstantial, it is necessary to keep in mind that antiidiotypic antibodies may also add to glomerular immune deposits and potentially could contribute to the chronicity of some forms of immunologic nephritis. The fate of the majority of immunologic nephritides is a slow progression toward end-stage renal insufficiency. Although in most cases the etiology remains to be determined, it is generally felt that a better understanding of the initial immune dysregulation may lead to a greater possibility of control and cure. In this perspective, new directions of research, such as the one reviewed here, should be considered. Modulation of the damaging autoimmune responses in SLE or Goodpasture's Syndrome might be possible. For instance, the identification of a cross-reacting idiotype among anti-GBM antibodies would be the first step for a possible future use of natural or synthetic idiotypes for autovaccination purposes. Antiidiotype antibodies, particularly in the form of monoclonal chimaeric (mouse/human) hybridomas, could be utilized for passive immunosuppression, particularly in combination with plasmapheresis, with or without conventional immunosuppressive drugs. Clearly, this is part of a long-term process that may or may not be realized. The success of new forms of specific immunologic treatment for kidney diseases may ultimately depend upon ongoing efforts in the study of the new molecular aspects of regulation of potential nephritogenic immune responses.

Animals↗

PubMed1986

Effects of the anaphylatoxin, C5a, on renal and glomerular hemodynamics in the rat.

The effects of intrarenal infusion of the complement-derived anaphylatoxin, C5a, upon glomerular hemodynamics were examined in the Munich-Wistar rat, a strain with glomeruli on the kidney surface. Human C5a (1.5 micrograms/min) or vehicle was infused into the left renal artery for 12 min, and glomerular capillary (PG) and Bowman's space pressures, nephron plasma flow (SNPF) afferent and efferent arteriolar protein concentrations, nephron filtration rate (SNGFR) and the glomerular ultrafiltration coefficient (LpA) determined. Human C5a infusion resulted in a reduction in SNPF due to increased efferent arteriolar resistance, and PG increased which maintained SNGFR constant. LpA was numerically lower but not significantly decreased. Infusion of porcine C5ades Arg decreased glomerular filtration rate and renal blood flow. No polymorphonuclear leukocytes were observed within glomerular capillaries of C5a infused rats, and rat leukocytes did not exhibit receptors for human C5a infused. Renal artery infusion of either human C5a or porcine C5a resulted in renal hemodynamic alterations and, as documented for human C5a, effects of C5a upon renal vascular resistance can be added to the known effect of C5a on the polymorphonuclear leukocyte.

Animals↗

PubMed1986

Direct antigen binding to glomerular immune complex deposits.

We evaluated the contribution of intrarenal factors in the increased renal accumulation of bovine serum albumin (BSA) in chronic serum sickness (CSS). Renal transplantation was used to study 125I BSA uptake (single and paired label techniques) in normal and CSS kidneys exposed to the same immunologic milieu. In CSS, the daily dose of BSA (dose 15 to 150 mg) was substituted with radiolabeled BSA. Uptake in washed kidney homogenates (24 hours) in the recipient's native CSS kidney varied from 0.29 to 38.40 micrograms/g of kidney (mean 11.70) compared to 0.09 to 2.19 micrograms/g (mean 1.01) in the transplanted normal kidney. The ratio of uptake in the CSS/normal kidney varied from 2.1 to 17.5. These findings indicated that intrarenal factors were important in renal uptake since both kidneys had been exposed to the same circulating immune complex load. Transplantation between "early" (nonproteinuric) and late (proteinuric) CSS rabbits again suggested intrarenal factors influence the uptake of 125I BSA immune complex components with late CSS kidney/early CSS kidney uptake ratios of 25 and 49 in the pairs examined. When CSS kidneys were transplanted into normal rabbits, the binding of 1 to 160 mg of radiolabeled BSA in the transplanted CSS kidney varied from 0.68 to 22.89 micrograms/g (mean 7.15) compared to 0.01 to 0.84 microgram/g (mean 0.18) in the normal rabbit's native kidney. The uptake in the CSS kidney always exceeded that in the recipient's normal kidney (ratio varied from 18 to 289). The binding of radiolabeled BSA in the CSS kidney was quantitatively similar to that found previously in the intact CSS rabbit.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1986

Decreased production of interferon-gamma by human neonatal cells. Intrinsic and regulatory deficiencies.

Human neonatal lymphocytes produced little macrophage activation factor in response to mitogens. This correlated with decreased production of interferon-gamma (IFN gamma): adult lymphokines contained 894.2 +/- 177.1 U/ml, whereas neonatal cord and peripheral lymphokines contained 66.9 +/- 17.0 and 116.7 +/- 29.6 U/ml by bioassay. Results by radioimmunoassay (RIA) for IFN gamma were similar. In contrast, the interleukin 2 content of cord lymphokines was greater (P less than 0.01) and that of neonatal peripheral blood lymphokines similar to that of adults. Interleukin 1 production and interleukin 2 receptor expression and affinity were similar for adult and neonatal cells. Interleukins 1 and 2 in amounts comparable to those in adult lymphokines did not increase production of macrophage activation factor or IFN gamma by neonatal cells. Neonatal cells did not contain intracellular IFN or degrade exogenous IFN. Excess suppressor activity was not found in neonatal cultures. Addition of IFN alpha, 10,000-50,000 U/ml of interleukin 2 or phorbol myristate acetate (PMA) to cord mononuclear cells or of adult monocytes or PMA to cord T cells increased IFN gamma production compared to cells stimulated with concanavalin A (ConA) alone. Nevertheless, under optimal conditions (T cells + PMA + Con A), adult cells produced much more IFN gamma (1,360 +/- 261 U/ml by RIA) than cord cells (122 +/- 37 U/ml). Staphylococcal enterotoxin A (SEA) stimulated cord cell IFN gamma production at low cell densities; nevertheless, adult cells produced more IFN in response to SEA 1,341 +/- 350 U/ml) than cord cells (350 +/- 33 U/ml). Decreased production of IFN gamma by neonatal cells appears to be due both to differences in their intrinsic capacity to produce IFN gamma and to differences in regulatory mechanisms.

Concanavalin A↗

PubMed1986

Variant aneurysms of the fenestrated basilar artery.

Two cases of aneurysm occurring on a fenestrated basilar artery are reported. One patient had a saccular aneurysm in the typical location at the vertebrobasilar junction at the proximal end of the fenestrated basilar segment. The aneurysm sac projected dorsally into the brain stem. The other patient had a blister-like aneurysm distal to a fenestration of the terminal basilar artery. The development of a distal aneurysm on a fenestrated basilar artery is predictable based on the reported morphology of the vessel wall in this vascular anomaly.

Adult↗

PubMed1986

Cerebral salt wasting after pituitary exploration and biopsy: case report.

We report a case of hyponatremia associated with volume depletion after pituitary exploration and biopsy. The presence of clinical dehydration precluded diagnosis of the syndrome of inappropriate secretion of antidiuretic hormone. The absence of a hypoadrenal state and the patient's response to volume reexpansion were consistent with a diagnosis of primary cerebral salt wasting.

Adult↗

PubMed1986

Intramedullary neurilemomas of the spinal cord: report of two cases and review of the literature.

Two patients harboring intramedullary neurilemomas of the spinal cord are presented. Published reports of these rare lesions and possible mechanisms of their origin are reviewed. Based on the authors' experience and review of the literature, they think that the treatment of choice for these rare lesions is laminectomy and resection and that intraoperative frozen section diagnosis is essential. Incorrect interpretation of the biopsy material that suggests an original diagnosis of infiltrating glioma, perhaps because a neurilemoma was not expected, has made second operations necessary.

Adult↗

PubMed1986

In situ cell kinetics studies on human neuroectodermal tumors with bromodeoxyuridine labeling.

Thirty-eight patients undergoing surgical removal of neuroectodermal tumors of the central nervous system were given a 1-hour intravenous infusion of bromodeoxyuridine (BUdR), 150 to 200 mg/sq m, to label tumor cells in the deoxyribonucleic acid (DNA) synthesis phase (S-phase). The excised tumor specimens were divided into two portions: one was fixed with 70% ethanol and embedded in paraffin and the other was digested with an enzyme cocktail to make a single-cell suspension. The paraffin-embedded tissues were stained by an indirect peroxidase method using anti-BUdR monoclonal antibody (MA) as the first antibody. Single-cell suspensions were reacted with fluorescein isothiocyanate (FITC)-conjugated anti-BUdR MA's for flow cytometric analysis. S-phase cells that had incorporated BUdR into their DNA were well stained by both methods. The percentage of BUdR-labeled cells, or S-phase fraction, was calculated in tissue sections by microscopic examination and in single-cell suspensions by flow cytometric analysis. The biological malignancy of the tumors was reflected in the S-phase fractions, which were 5% to 20% for glioblastoma multiforme, medulloblastoma, and highly anaplastic astrocytoma, but less than 1% in most moderately anaplastic astrocytomas, ependymomas, and mixed gliomas. Two juvenile pilocytic astrocytomas and two low-grade astrocytomas from children had high S-phase fraction despite the fairly benign and slow-growing nature of these tumors. These results indicate that the S-phase fraction obtained immunocytochemically with anti-BUdR MA's may provide useful information in estimating the biological malignancy of human central nervous system tumors in situ.

Adolescent↗

PubMed1986

The proliferative potential of human pituitary tumors in situ.

At the start of transsphenoidal microsurgery for removal of various types of pituitary adenomas, 21 patients received a 1-hour intravenous infusion of 5-bromodeoxyuridine (BUdR, 200 mg/sq m) to label tumor cells in the deoxyribonucleic acid (DNA) synthesis phase (S-phase). Excised tumor specimens were fixed in 70% ethanol and stained by the indirect peroxidase method using anti-BUdR monoclonal antibody as the first antibody. The percentage of BUdR-labeled cells, or S-phase fraction, was calculated for each specimen. The S-phase fraction was less than 0.1% in nine cases, 0.1% to 0.5% in seven, and greater than 0.5% in five. Except in two cases of Nelson's syndrome, in which it was greater than 1%, the S-phase fraction did not correlate with any other variable, including patient age, tumor size, or the duration of signs and symptoms. The small S-phase fraction of most of the pituitary adenomas correlates well with the clinical behavior of these tumors, which grow much more slowly than other kinds of brain tumors such as gliomas. However, the S-phase fractions varied by as much as one order of magnitude. The higher S-phase fractions may reflect aggressive and invasive growth. These results indicate that immunohistochemical studies of cell kinetics using BUdR and anti-BUdR monoclonal antibodies may provide information about the biological characteristics of pituitary adenomas which could lead to the design of appropriate treatment regimens (including surgery, radiation therapy, and chemotherapy) for individual patients.

Adenoma↗

PubMed1986

Intracranial arachnoid cysts in children.

The clinical and radiographic findings, surgical treatment, and outcome in 16 pediatric patients with intracranial arachnoid cysts are reviewed. The clinical presentation reflected the anatomical location of the lesions. Computerized tomography or magnetic resonance imaging scans were diagnostic in all cases. Of the nine cysts treated primarily or secondarily by craniotomy for fenestration and drainage into the basilar cisterns, five recurred. Cyst-peritoneal shunting led to diminished cyst size and clinical improvement in all seven cases in which it was used as the initial treatment and in all four cases in which fenestration had been unsuccessful. The results in this series show that cyst-peritoneal shunting is the treatment of choice for most intracranial arachnoid cysts in children.

Adolescent↗

PubMed1986

Surgical management of craniopharyngiomas. A review of 74 cases.

A series of 74 patients with craniopharyngiomas were treated during a 15-year period. Of the 74 patients, 40 were males and 34 were females, with a mean age of 27 years (range 3 to 65 years). Twenty-eight patients (38%) were less than 18 years of age. Remission was defined as clinical improvement with stable ophthalmological and neurological status, radiological evidence of a decrease in tumor size, and either a continued decrease or a stable tumor size on follow-up radiological evaluations. A fair result was considered remission with new neurological deficits related to surgical intervention. All other results were considered a failure. The mean follow-up period in this study was 4 years, with 100% of the patients monitored. In children, the most common presentation was that of growth failure (93%). In adults, sexual dysfunction was the most common presentation, with 88% of males presenting with impotence or marked decrease in sexual drive, and 82% of females presenting with primary or secondary amenorrhea, often associated with galactorrhea. Considering the pediatric and adult populations together, the most common presenting symptom was visual dysfunction, with 71% of patients presenting in this manner. Fifty percent of patients presented with severe headache. The most frequent preoperative finding was a visual field defect, with 72% of patients so affected; 42% of patients had preoperative hypothyroidism and 24% had hypoadrenalism. Diabetes insipidus was present preoperatively in 23%. Hydrocephalus was uncommon, being present in only 15%. A subfrontal craniotomy was used in 47% of patients, a transsphenoidal approach in 39%, a subtemporal approach in 11%, a transcallosal approach in 5%, and a suboccipital craniectomy in 2%. Multiple procedures were required in 15% of patients in order to provide significant relief of compressive symptomatology. The results of therapy indicate that total tumor removal was deemed to have been achieved in only seven patients, six of whom have had no recurrence. However, 91% of patients are in remission, one had a fair result, and two died as a direct result of surgical intervention. One patient died from uncontrolled disease, and three patients died from unrelated causes. The results of this study indicate that radical subtotal removal followed by radiotherapy is an acceptable treatment for craniopharyngioma.

Adolescent↗

PubMed1986

Development of multiple lesions during radiation therapy and chemotherapy in patients with gliomas.

To determine the percentage of patients who developed multiple central nervous system (CNS) gliomas during postoperative radiation therapy and chemotherapy, the authors reviewed the records of 1047 patients treated between December 2, 1976, and August 16, 1985, who had an original diagnosis of supratentorial glioblastoma multiforme or other anaplastic glioma. The occurrence of multiple lesions was verified by neurodiagnostic studies (computerized tomography or myelography) or by findings at operation or autopsy. Twelve patients (1.1%) who presented with multiple lesions were excluded from this analysis. There were 405 patients with glioblastoma multiforme; their median age was 46.5 years (range 22 to 70 years). Eighteen (5%) of these patients had multiple CNS lesions, five of which were in the spinal cord. The median time from diagnosis to detection of the second lesion in this group was 59.5 weeks (range 10 to 182 weeks). There were 630 patients with anaplastic glioma (which included mixed malignant glioma and highly anaplastic, gemistocytic, moderately anaplastic, and anaplastic astrocytomas); their median age was 30 years (range 2 to 62 years). Fifty-four (8.6%) of these patients had multiple lesions, 10 of which were in the spinal cord; only one case of extraneural metastasis was found. The median time from diagnosis to detection of the second lesion in this group was 101 weeks (range 14 to 459 weeks). These results show that more than 90% of CNS gliomas recur at the site of the original tumor. Considering the high frequency of intellectual dysfunction after whole-brain radiation therapy, the use of focal radiation fields appears to be the most judicious approach to the treatment of patients with gliomas.

Adult↗