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Biomedical subjects

R E Wilson

Publications and source records attributed to R E Wilson.

At least 109 records · Page 6Linked to original sources
PubMed1983

Serial circulating immune complex levels and mitogen responses during progressive tumor growth in WF rats.

Inbred male WF rats were given im injections of one of two antigenically and histologically distinct syngeneic tumor isografts, adenocarcinoma DMH-W 163 or spontaneous renal cell carcinoma SPK. Serum and peripheral blood lymphocytes were harvested from tumor-bearing and normal age-matched controls before and after isograft challenge at weekly intervals. Serial circulating immune complex (CIC) levels were quantitated by polyethylene glycol (PEG) insolubilization. T-cell mitogen responses to phytohemagglutinin (PHA) and concanavalin A (Con A) were followed serially. Tumor growth was measured at least weekly. PEG-CIC values rose early after tumor injection, increased with tumor growth, and declined in some animals just before death. Mitogen response to PHA was significantly decreased in isografted tumor-bearing rats, particularly at later stages of tumor development, compared to normal uninoculated controls. Responses to Con A were variable, and suppression was not always seen in tumor bearers. In animals that did not have progressive tumor growth after isograft injection, PEG-CIC levels did not change and responses to PHA were not suppressed. Patterns of CIC change and responses to PHA were not affected by differences in tumor histology or growth rates. Thus serial CIC levels measured by the PEG assay correlate with tumor growth and precede nonspecific suppression of T-cell mitogenic response in these animal tumor models.

Animals↗
PubMed1982

Effects of supernatants of polymorphonuclear neutrophils recruited by different inflammatory substances on mitogen responses of lymphocytes.

Two different substances, glycogen and thioglycollate, were used to recruit early peritoneal exudate cells (4h). In the acute phase of the inflammatory response the cellular infiltrate is large, and the predominant cell (greater than 95%) is the polymorphonuclear neutrophil. Supernatant had differing effects on lymphocyte responses to the mitogens PHA and LPS, also carried out in serum-free media, depending on recruiting substance and time of culture. While glycogen-recruited PMN supernatant (GPMN-S) always enhanced splenocyte responses to PHA, thioglycollate-recruited cells (TPMN-S) did not produce an enhancing factor until the cells had been in culture for 24 h. Whereas GPMN-S enhanced the splenocyte response to LPS only after 1 or 4 h of culture, TPMN-S failed to have any significant effect. Thymocyte responses to PHA were facilitated by all supernatants. Dilution of the soluble PMN factors resulted in a suppressive effect on splenocyte responses to both PHA and LPS, regardless of whether PMN were recruited by the thioglycollate or glycogen or of the time of cell incubation. These results indicate that PMN-rich cell populations of different types of activity are recruited by glycogen and thioglycollate and that these cells produce factors capable of potentiating, enhancing, or suppressing responses to T- or B-cell mitogens by normal syngeneic lymphocytes.

Animals↗
PubMed1982

Surgical treatment of low grade soft tissue sarcomas.

Nineteen patients who have undergone surgical resection of low grade soft tissue sarcomas were retrospectively reviewed. Four patients received additional radiation therapy, and 15 did not. Of the 15 patients treated by surgery alone, 4 had positive margins in the original specimen; all 4 had local recurrence within a mean of 42 months. Eleven patients had negative margins. Ten have had no recurrence in a mean of 40 months. One patient had local recurrence at 36 months. Two of the four patients with positive margins were reoperated on and in achieving negative margins have remained disease-free a mean of 84 months. Three patients receiving additional postoperative radiation therapy had positive margins, and all had recurrence in a mean of 36 months. One patient with negative margins who also received radiation therapy is disease-free at 144 months. It appears that tumor-positive margins are associated with a high likelihood of local recurrence, whereas negative margins appear associated with a long disease-free interval and possible cure. Radiation therapy to positive margins did not prevent local recurrence.

Adolescent↗
PubMed1982

Abnormal regulation of parathyroid hormone release by calcium in secondary hyperparathyroidism due to chronic renal failure.

Dispersed parathyroid cells were employed to study calcium-regulated parathyroid hormone (PTH) release in severe secondary hyperparathyroidism due to chronic renal insufficiency. Cell preparations were obtained from 16 parathyroid glands of 6 patients undergoing subtotal parathyroidectomy for parathyroid bone disease and/or hypercalcemia. The effects of increasing ambient calcium concentration on immunoreactive PTH release in vitro were assessed and compared with results observed in cells prepared from 7 adenomas and 6 normal parathyroid glands. There was no difference in maximal PTH release for the 3 types of tissue (mean +/- SEM, 8.48 +/- 1.9 , 8.1 +/- 3, and 10.1 +/- 0.78 ng/10(5) cells. h respectively). In 14 of 16 hyperplastic glands, 6 of 7 adenomas, and all of the normal glands, PTH release was inhibited more than 50% by 2-3 mM calcium (suppressible glands). Of the normal glands, half of the maximal inhibition of PTH release (the set-point) occurred at less than 1.03 mM calcium in 5 of 6 cases. In 12 of 14 suppressible hyperplastic glands and all of the 6 suppressible adenomas, on the other hand, the set-point was 1.03 mM or higher (p less than 0.01 and P less than 0.002, respectively). Thus, in severe secondary parathyroid hyperplasia due to chronic renal insufficiency, there is frequently an increase in the set-point for calcium without a change in the maximal secretory rate per cell. Abnormal calcium-regulated PTH release at the cellular level, therefore, is not limited to parathyroid neoplasia (i.e. adenoma or primary hyperplasia), but may occur in secondary hyperplasia as well.

Adenoma↗
PubMed1982

Peritoneal macrophage alterations caused by naturally occurring mouse hepatitis virus.

During routine harvest of murine resident peritoneal cells for macrophage function assays the authors recently noted that mice showed a 3-4-fold spontaneous increase in number of peritoneal cells within 1 week of being placed in one of their animal rooms. While the mice appeared clinically normal, the collected macrophages had highly convoluted membranes, showed enhanced spontaneous tumor cell killing, and showed increased erythrophagocytosis. Histopathologic findings included mild peritonitis and occasional foci of individual hepatocyte necrosis. The results of routine murine serologic studies and bacterial cultures of the peritoneal cavity were negative. Immunosuppressed mice placed in this room showed severe hepatic necrosis within 4 days, and ultrastructural particles characteristic of corona virus could be demonstrated in the necrotic foci. Mouse hepatitis virus (MHV) was isolated from these livers. Untreated mice showed positive MHV titers, as detected by the enzyme-linked immunoabsorbent assay (ELISA) after 21 days in the room. This episode demonstrates that MHV have profound effects on macrophage parameters while causing few clinical signs or histopathologic alterations. Secondly, the complement fixation assay for MHV as included in routine viral screens appears relatively insensitive for detecting outbreaks of MHV.

Animals↗
PubMed1982

Circulating immune complex levels in patients with gestational trophoblastic neoplasia.

The clinical course, human chorionic gonadotropin (HCG) levels, and serial circulating immune complex (CIC) levels in 21 patients with gestational trophoblastic neoplasia (GTN) were correlated for the evaluation of the relationship between CIC levels and trophoblastic tumor burden. CIC levels were normal in 18 of 21 patients at the time of presentation, and 2 of 3 patients who presented with elevated CIC levels had significant comorbid disease (toxemia and hepatitis). Nine patients were followed into gonadotropin remission, and all 9 developed an increase in CIC levels at the time of remission. It was concluded that CIC, at least as measured by two antigen-nonspecific techniques, is generally not elevated at initial presentation in the patient with GTN; this lack of an elevation is probably due to marked tumor antigen excess. Thus the in vivo importance of CIC as a "blocker" of host antitumor response at this stage is doubtful. After effective treatment as HCG levels return to normal, the demonstrated elevation in serial levels of CIC may reflect a return of adequate host immune response at a time of minimal tumor burden.

Adolescent↗
PubMed1981

Anticoagulants, venous thromboembolism, and the cancer patient.

The records of 32 cancer patients who were treated with heparin sodium and warfarin sodium for thromboembolic disease were reviewed. Standard techniques for anticoagulation were neither safe nor effective. Sixteen patients experienced 21 different hemorrhagic complications. Eight patients had major hemorrhages that led to cessation of therapy or death. Six of 32 patients had pulmonary embolisms while receiving anticoagulants. It is suggested that venous interruption may be a safer and more effective method of prophylaxis against pulmonary embolism in cancer patients.

Adolescent↗
PubMed1981

Effect of major small bowel resection on dimethylhydrazine-induced bowel carcinogenesis.

We have investigated the effect of distal small bowel resection on chemically induced tumors of the gastrointestinal tract in Wistar/Furth (W/Fu) rats. Dimethylhydrazine (DMH) (20 mg/kg sc once weekly x 16) was commenced 3 months after rats underwent resection of the distal 30 cm of small bowel (one-third resection) or after sham small bowel resection (controls). Fifty weeks after the start of DMH administration, tumors were found in 15 of 25 animals who underwent small bowel resection compared to 9 of 31 animals in the control group (P less than 0.05). After small bowel resection, 8 of 15 tumors occurred at the site of anastomosis but no anastomotic tumors were seen after sham resection. In addition, tumors were larger and more invasive after small bowel resection. These data indicate that major small bowel resection potentiates DMH induced-intestinal carcinogenesis.

Adenocarcinoma↗
PubMed1981

Immunogenicity and cross-protection among B16 melanoma variants with differing proclivities to metastasize.

We report here the lack of any relationship between immunogenicity and the potential to metastasize among four B16 melanoma variants. Groups of C57BL/6J mice were immunized with one of four B16 variant lines (maintained by serial IM passage) that were shown in separate experiments to produce the following incidences of pulmonary metastases four to six weeks after isograft excision: M1, 10%-15%; M2 10%-20%; M3, 75%-80%; and M4, 75%-90%. After immunization, mice were challenged with one of the four variant lines in a crisscross fashion. Two challenge doses for each line were chosen on the basis of earlier experiments showing 100% and 50% challenge tumor take in nonimmunized animals. Despite earlier work published from this laboratory showing that splenocytes harvested from immunized mice could distinguish antigenic differences among the B16 variants, we could find no significant difference in immunogenicity or cross-protection among the lines regardless of their metastatic potential. We conclude that no correlation exists between the antigenic differences shown by in vitro splenocyte-mediated cytotoxicity assays among the B16 variants and in vivo immunogenicity or cross-protection experiments. Futhermore, the relationship (if any) between immunogenicity and the ability to metastasize among these B16 variants is not straightforward.

Animals↗
PubMed1981

Abnormal calcium-regulated PTH release in normal parathyroid tissue from patients with adenoma.

The regulation of parathyroid hormone (PTH) secretion by calcium was studied in normal and abnormal parathyroid tissue from five patients with a parathyroid adenoma. Dispersed cells were prepared from the adenoma and from a portion of a normal parathyroid gland and were incubated for two hours with varying concentrations of calcium. PTH release as a function of the concentration of calcium was determined by radioimmunoassay (C-terminal). Cells from the normal glands showed a lower set-point for calcium (the concentration of calcium causing half of the maximal inhibition of PTH release) than those from the adenomas in four of five cases. Moreover, both set-point and maximal PTH release at low concentrations of calcium were significantly lower in normal glands from patients with an adenoma than in normal glands from patients with normal calcium homeostasis (0.77 +/- 0.04 [SEM] versus 0.99 +/- 0.03 mM calcium and 3.4 +/- 0.43 versus 10.1 +/- 0.78 ng/10(5) cells/hr, respectively). These observations may explain, in part, the transient hypocalcemia frequently seen in patients after removal of a parathyroid adenoma. In addition, they suggest that the set-point for calcium and maximal PTH release in normal parathyroid tissue may be altered by prior exposure to chronic hypercalcemia or other physiologic variables. Finally, the "normal" set-point that we have noted previously in parathyroid tissue from some patients with primary parathyroid hyperplasia may be inappropriately high for the hypercalcemia seen in those cases.

Adenoma↗
PubMed1981

Evaluation of palliative procedures for pancreatic cancer.

In a retrospective review of 51 patients undergoing palliative procedures for carcinoma of the pancreas from 1974 to 1979, cholecystoenterostomy was as effective as choledochoenterostomy. Patients with loops had the same incidence of cholangitis as those with Roux-Y limbs. Prophylactic gastroenterostomy was not performed routinely. Few patients needed a later gastroenterostomy for progressive cancer.

Aged↗
PubMed1981

Application of polyethylene glycol turbidity assay to detection of circulating immune complexes in cancer patients.

A rapid, reproducible immune complex screening assay was used to quantitate levels of circulating immune complexes in the sera of normal subjects, patients with documented increases in immune complexes from rheumatoid arthritis, patients with clinically or microbiologically documented infections, and patients with cancer. Although wide variations in individual values within the groups were noted and the concurrent elevation of polyethylene glycol-circulating immune complex levels by infection was documented as expected, significant differences were found in the values in patients with cancer compared with those in normal subjects. The overall clinical application of polyethylene glycol-circulating immune complex screening is discussed and current application of screening of serial sera samples from individual patients for correlation with measurable tumor volume is proposed.

Antibodies, Neoplasm↗
PubMed1981

In vivo and in vitro effects of xenogeneic immune ribonucleic acid in patients with advanced renal cell carcinoma: a phase I study.

Based upon demonstration in our laboratory of repeated prevention of pulmonary metastases by adjuvant immune ribonucleic acid in animal preparations, xenogeneic immune ribonucleic acid was given in a phase I study to patients with advanced renal cell carcinoma. Six patients were treated with intravenous infusions of autologous lymphocytes incubated in vitro with immune ribonucleic acid extracted from splenocytes of guinea pigs immunized with the patient's own tumor. Serial peripheral blood lymphocytes were obtained during and after each treatment with immune ribonucleic acid for in vitro evaluation of cell-mediated cytolysis by 51chromium release assay and 125iodine iododeoxyuridine assay against allogeneic renal cell carcinoma targets and melanoma targets. Neither toxicity nor enhancement of tumor growth was observed. All patients demonstrated significantly increased cell-mediated cytolysis against allogeneic renal cell carcinoma targets but no change against melanoma targets. Increased cell-mediated cytolysis could be demonstrated in individual blood samples after incubation with immune ribonucleic acid. Further, progressive in vivo effect was demonstrated in in vitro assay of serial peripheral blood lymphocytes before each successive exposure to immune ribonucleic acid. Increased cell-mediated cytolysis persisted in peripheral blood lymphocytes up to 9 months after therapy. Although without controls 1 patient had complete response and 2 patients had partial responses (8 to 18 months). Two patients had stabilization of the disease for 3 to 4 months and 1 patient had progression of cerebral metastases. One patient is alive 24 months after therapy. These results would favor the institution of a randomized prospective trial in patients with advanced renal cell carcinoma or lesser tumor burdens.

Adenocarcinoma↗
PubMed1981

Human gamma-lipotropin radioimmunoassay: identification of immunoreactive gamma-lipotropin in human plasma and tissue.

Disagreement exists concerning the relative contributions to total plasma immunoreactive human lipotropin (hLPH) made by h beta LPH and its amino-terminal fragment, h gamma LPH [h beta LPH-(1-58)]. Using an antiserum (R1547) which requires the free COOH-terminal Asp58 residue of h gamma LPH for full affinity and reacts only 1% as well with h beta LPH and antisera (R3 and G106) that react with both LPHs, we examined gel chromatography eluate fractions of plasma extracts from one normal subject under basal conditions and another after metyrapone administration, of plasma or plasma extracts from patients with ACTH/LPH hypersecretion of various causes, of an extract two normal pituitary glands, and an extract of an ectopic ACTH/LPH-secreting tumor. Immunoreactive h gamma LPH was always a major, frequently the predominant, and sometimes the only immunoreactive LPH observed. We also observed in plasma or tissue of two patients with ectopic ACTH/LPH syndrome a peptide whose immunoreactivity and apparent molecular size were consistent with those of octadecapeptide human beta MSH, a molecule that is not thought to exist in normal man. These studies demonstrate that h gamma LPH is a major LPH component in plasma and tissues and indicate that the h gamma LPH RIA provides a reliable estimate of the h gamma LPH concentration in plasma without prior chromatography.

ACTH Syndrome, Ectopic↗