Search PubMed⌕ Search

Biomedical subjects

G Steele

Publications and source records attributed to G Steele.

At least 127 records · Page 7Linked to original sources
PubMed1984

Particle size stability of intralipid and mixed total parenteral nutrition mixtures.

The determination of the particle size of Intralipid fat emulsions by the non-perturbing method of photon correlation spectroscopy has been extended to include particle size determination using the Coulter counter and optical microscopy. Although little increase in particle size in 3-litre bags containing total parenteral nutrition mixtures was observed with the methods involving large dilutions, creaming was observed and optical microscopy showed aggregation and some coalescence to have taken place. The problem of re-dispersion upon dilution of aggregated (but not coalesced) fat emulsions makes direct optical observation essential in assessing the stability and safety of such fat emulsion mixtures. The effect of electrolytes (NaCl and CaCl2) on creaming, particle size and electrophoretic mobility showed both minimum stability and minimum zeta potential at 3 X 10(-3) mol dm-3 CaCl2 and at 2.5 X 10(-1) mol dm-3 NaCl. Thus, these maximum levels for electrolytes in total parenteral mixtures are indicated.

Adult↗
PubMed1984

Identification of material with paternal HLA antigen immunoreactivity from purported circulating immune complexes in patients with gestational trophoblastic neoplasia.

Circulating immune complex(es) (CIC) have been shown to rise progressively only when patients with hydatidiform molar pregnancy enter gonadotropin-documented remission. The CIC in 3 patients with gestational trophoblastic neoplasia (GTN)--1 with hydatidiform mole and 2 with choriocarcinoma--were characterized. Their clinical course was monitored by serial antigen-nonspecific polyethylene glycol (PEG) 6000-CIC assay and simultaneous human chorionic gonadotropin (HCG) assay from presentation until sustained gonadotropin-documented remission. As serial HCG progressively decreased to normal following surgical or chemotherapeutic reduction in tumor burden, PEG-CIC concurrently rose. Serum obtained at or near peak PEG-CIC levels was precipitated by 3.75% PEG 6000 and fractionated by column chromatography on Sephadex G-200 (exclusion limit, greater than 600,000 mol wt) in glycine-HCl and 1 M NaCl buffer at pH 2.8. None of the 5 elution fractions obtained from the 3 patients contained HCG or anti-HCG activity. However, in the hydatidiform molar patient, fractions 1 through 3 (mol wt greater than 67,000--and containing immunoglobulin) were shown to competitively inhibit complement-dependent antibody lysis on 1 of 4 paternal HLA haplotype (AW32) targets. In 2 of the 3 patients studied, low-molecular-weight fractions (not containing immunoglobulin) significantly inhibited reference anti-HLA binding of antisera directed against only 1 of 4 paternal HLA haplotypes. The immunospecificity of this inhibition was confirmed by criss-cross control assays in which elution fractions obtained from both of these patients were tested for inhibition of lymphocytolysis of both sets of paternal lymphocytes. None of these fractions were immunoreactive to maternal HLA haplotypes. Further analysis of serum from the hydatidiform molar patient revealed that no free complement-fixing antibody against paternal antigens could be found by conventional screening assays in unfractionated patient sera. Three of 4 paternal HLA antigens or non-complement-fixing anti-HLA immunoglobulin was detected in unfractionated pretreatment, treatment, and remission sera of the hydatidiform molar patient. Only in this patient's remission sera was unbound AW32 antigen or non-complement-fixing anti-AW32 antibody detected. These data demonstrate the successful characterization of at least 1 specific antigen fractionated from a tumor-associated immune complex. The implication that some patients with GTN may recognize and react to immunogenic paternal HLA antigens as part of their successful response to therapy for trophoblastic tumor is discussed.

Antigen-Antibody Complex↗
PubMed1984

Specific active immunotherapy with butanol-extracted, tumor-associated antigens incorporated into liposomes.

With the use of whole tumor cell vaccines in a rat colon cancer minimal residual disease model, we have recently demonstrated that although tissue type-specific tumor immunogens protect against recurrence in the absence of histocompatibility differences, these immunogens offer no predictable tumor-specific protection in the presence of such differences. We have therefore begun to test whether syngeneic and allogeneic rat colon cancer tumor-associated antigens (TAAs), when incorporated into the bilayers of liposomes, could function as effective immunogens in immunotherapy and immunoprotection models. Male Wistar/Furth (W/Fu) rats were inoculated with 5 X 10(6) DMH-W163 colon cancer cells. All nonimmunized animals died of widespread metastases within 2 weeks of complete local tumor resection. In experimental groups, four methods of immunotherapy were used after resection: (1) irradiated whole tumor cells, (2) butanol-solubilized membrane extracts containing TAA only, (3) liposomes only, and (4) liposomes containing TAA. Only animals receiving TAA incorporated into liposomes had a significant increase in survival (p = 0.026). Thirty percent remain disease-free 6 months later. In additional experiments, Buffalo rats were challenged with 1 X 10(6) Buffalo rat colon adenocarcinoma cells after immunization by irradiated whole tumor cells or liposomes and butanol-extracted colon cancer TAAs. Only animals in the group immunized with TAA incorporated into liposomes were significantly protected from subsequent tumor isograft challenge. These data provide evidence of a way to present solubilized colon cancer-associated immunogens that may be applicable in a more clinically relevant, allogeneic setting.

1-Butanol↗
PubMed1984

Effects of specific active immunization on tumor recurrence following primary tumor resection in WF rats with 1,2-dimethylhydrazine-induced bowel cancer.

Primary gastrointestinal tumors were induced in male WF rats by 16 weekly sc injections of 1,2-dimethylhydrazine [(DMH) CAS: 540-73-8; 20 mg/kg/wk]. Twenty-four to 28 weeks after the start of DMH injections, all rats were surgically explored and gastrointestinal tumors were resected. Rats with no remaining microscopic disease after operation were immunized with one of four tumor isografts. The first isograft, DMH-W163, is a poorly differentiated mucinous adenocarcinoma explanted from a colon cancer in a DMH-treated animal. It has been shown to possess antigens that cross-react with other DMH-induced bowel adenocarcinoma isografts. The second isograft, DMH-W49, is a carcinosarcoma explanted from a DMH-treated primary colon cancer. It has intermediate antigenic cross-reactivity with other colon adenocarcinoma isografts in the WF model. The third isograft, DMH-W15, is a sarcoma explanted from a DMH-induced colon cancer that does not possess antigens cross-reactive with other DMH-induced colon adenocarcinomas. The fourth isograft, SPK, is a spontaneous (non-DMH-induced) renal cell carcinoma that is immunogenic but should not contain tissue-type-specific antigens cross-reacting with the bowel cancers. Immunized rats received three sc weekly injections of 1 X 10(3) irradiated cells. Concomitant control rats received no immunization after resection of the primary tumor. Within 24 weeks of primary tumor resection, 12 of 16 (75%) rats not immunized had tumor recurrence. Only 8 of 24 (34%) rats immunized with DMH-W163 had tumor recurrence (P less than .025 compared to controls). Fifty percent of animals (10/20) immunized with the carcinosarcoma DMH-W49 had a recurrence. Animals immunized with the non-cross-reacting DMH-W15 sarcoma isograft had a recurrence rate similar to that of controls (16/20, 75%). The rats immunized with SPK were not protected from recurrence. Twelve of 19 (63%) had a recurrence at or near the suture line within 24 weeks following primary tumor resection. These results confirm that adjuvant immunotherapy can decrease the rate of recurrence following primary tumor resection in this model. In addition, immunogens that possessed tissue-type-specific antigens were more effective in preventing tumor recurrence than those that did not.

1,2-Dimethylhydrazine↗
PubMed1983

Gut-associated lymphoid tissue and dimethylhydrazine-induced colorectal carcinoma in the Wistar/Furth rat.

Although gut-associated lymphoid tissue in the form of discrete lymphoid patches (LP-GALT) in mammalian intestine in most prominent in the distal ileum, appendix, and, in some species, the cecal appendage, LP-GALT can be found throughout the intestinal tract. LP-GALT appears as single or multiple subepithelial lymphoid follicles covered by a specialized, structurally unique epithelium. In the colon of the Wistar/Furth (W/Fu) rat, LP-GALT appears as aggregates of follicles, or lymphoid patches, that can be detected macroscopically. We studied the relationship between 1,2-dimethylhydrazine- (DMH) induced colon carcinomas and the lymphoid patch associated epithelium in these animals. In addition, we defined the normal distribution of colonic lymphoid patches in both DMH-treated and control rats. Patches were found macroscopically and confirmed by histologic examination at five constant sites: lower pole of cecum, proximal ascending colon, the major colonic flexure, mid descending colon, and the rectosigmoid. There are also the predominant sites of DMH induced carcinomas in W/Fu rats. In 120 DMH-treated animals, 109 colon carcinomas were found. Eight percent were in the lower pole of the cecum, 56% in the proximal ascending colon, 16% at the major flexure, 15% in the mid descending colon, and 5% in the rectosigmoid. Lymphoid patches could often be detected histologically in association with DMH-induced tumors. The depth of tumor invasion was found to correlate inversely with our ability to identify tumor-associated lymphoid patches suggesting that tumors arising at the anatomical sites were lymphoid patches occur progressively destroyed them. Of colon tumors confirmed histologically to be associated with lymphoid patches, 88% were superficial lesions confined to the submucosa and 12% were more extensive but confined to the bowel wall. No lymphoid patches could be found associated with tumors that extended through the bowel wall. Thus, DMH-induced colon carcinomas in W/Fu rats arise at sites containing preexisting LP-GALT with associated specialized epithelium.

Animals↗
PubMed1983

Circulating immune complexes in patients with colorectal cancer.

We have attempted to better define host humoral immune response in neoplasia by quantitating serial circulating immune complex values before and after surgery in patients with primary or metastatic colorectal cancer. Circulating immune complex levels were correlated with serial carcinoembryonic antigen values and tumor courses in patients with primary resectable colorectal cancer (four patients), resectable liver metastases (three patients), diffuse liver metastases treated with regional chemotherapy (three patients), and untreated intrahepatic (one patient) and extrahepatic metastases (one patient). Circulating immune complex levels, as measured by an antigen-nonspecific assay, which utilized 4 percent polyethylene glycol insolubilization, were increased in all patients at presentation (734 delta OD450 +/- 381) when compared with normal human control sera (202 +/- 4, p less than 0.05). No particular relation was found between presenting circulating immune complex levels and tumor burden. Progressive circulating immune complex increases were demonstrated only in patients whose tumors were either completely removed or dramatically responded to regional therapy (that is, when the tumor antigen load, as reflected by the carcinoembryonic antigen value, rapidly diminished). Serum samples obtained at times of presumed antibody excess in the patients with gastrointestinal cancers were found to contain unexpectedly high concentrations of IgA. We believe these data demonstrate the kinetics of circulating immune complex change during tumor course and they have allowed us to begin to identify circulating immune complex components in patients with colorectal cancer. The results confirm our earlier findings in patients with gestational tumors and differ from accepted relations between immune complexes and tumor growth.

Antigen-Antibody Complex↗
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↗
PubMed1983

Circulating immune complex levels in patients with molar pregnancy.

Circulating immune complex levels were measured in patients with molar pregnancy to investigate the relationship between circulating immune complex and trophoblastic tumor burden. When 27 (87%) of 31 patients with molar pregnancy were first seen, circulating immune complex values were in the normal range. Three of the 4 patients with elevated levels had concurrent medical illness. Eighteen patients were followed with serial measurements until gonadotropin remission was achieved and all 18 patients developed increased levels as they entered remission (P less than .001). Circulating immune complex values remained elevated during gonadotropin remission from 6 to 16 weeks and then declined to initial levels. Further investigation should be undertaken to evaluate possible interactions between circulating immune complex and host immune defenses.

Antibody Formation↗
PubMed1983

Evidence for an adenoma-carcinoma sequence in dimethylhydrazine-induced neoplasms of rat intestinal epithelium.

Carcinogen-induced primary intestinal adenocarcinomas serve as a useful animal model for human colonic adenocarcinomas. Although striking similarities between this model and the human disease state exist, there are also troublesome discrepancies-a major one being the reported lack of an adenoma-carcinoma sequence in the experimental model. However, the original morphologic descriptions of these experimental neoplasms predated the development of presently accepted morphologic criteria that have been used to describe the adenoma-carcinoma sequence in humans. Therefore, the authors reevaluated the structural evolution of dimethylhydrazine-induced rat intestinal neoplasms, using the same criteria that were recently applied to evaluate human colonic adenocarcinomas. Such an approach shows that many dimethylhydrazine-induced intestinal adenocarcinomas have peripheral foci of adenomatous epithelium associated with them. In addition, the frequency of this association correlates inversely (P less than .001) with the depth of invasion. These findings are comparable to those which, in humans, have been used as evidence supporting the adenoma-carcinoma sequence. Thus, when assessed with equivalent criteria, dimethylhydrazine-induced intestinal adenocarcinomas appear to be similar, not dissimilar, to human colonic adenocarcinomas in their structural evolution. These data suggest that, at least in part, dimethylhydrazine-induced intestinal adenocarcinomas arise in foci of preexisting adenomatous epithelium.

Adenocarcinoma↗
PubMed1982

Pharmacologic studies on the dibutyl and gamma-monobutyl esters of methotrexate in the rhesus monkey.

The pharmacokinetics and metabolism of dibutyl methotrexate (DBMTX) and gamma-monobutyl methotrexate (gamma-MBMTX) were studied in Rhesus monkeys. When a bolus IV dose of either [3H]DBMTX or [3H] gamma-MBMTX was given, the principal species in serum for up to 1 h was the monoester, with MTX accounting for less than 10% of the total radioactivity. Products other than gamma-MBMTX and MTX were formed in substantial amounts with DBMTX, but not with gamma-MBMTX. Total radioactivity recovered in the bile 5 h after [3H]DBMTX injection accounted for 32% of the administered dose, indicating high hepatic extraction for this lipophilic compound. Serum and CSF levels of unchanged gamma-MBMTX, as well as of MTX arising via esterase cleavage, were measured by HPLC after IV infusion of gamma-MBMTX (10 g/m2). Efflux of monoester from CSF was slower than disappearance from serum. However, gamma-MBMTX levels in CSF were no higher than could be attained by infusing MTX itself at the same dose rate. While CSF/serum ratios were ca. 10-fold higher for gamma-MBMTX than for MTX, this difference could be explained on the basis of the very different affinities of the two compounds for serum proteins. HPLC analysis of serum processed by methanol precipitation as opposed to ultrafiltration of the proteins showed gamma-MBMTX to be greater than 99% bound, whereas for MTX this value was 50% or less. When gamma-MBMTX and MTX levels measured after ultrafiltration were corrected for this difference in serum protein binding the total amount of the two drugs in serum became almost equivalent.

Animals↗
PubMed1982

CEA monitoring among patients in multi-institutional adjuvant G.I. therapy protocols.

The Gastrointestinal Tumor Study Group (GITSG) has since 1975 included protocols for monitoring carcinoembryonic antigen (CEA) levels in its colorectal cancer adjuvant trials. Among the 563 patients on the colon cancer study (GI 6175) and the 207 patients on the rectal cancer study (GI 7175), one third had preoperative CEA determinations and more than 90% had some postoperative CEA monitoring. Colon cancer patients whose preoperative CEA was greater than 5 ng/ml had a greater probability of recurring than those whose values were lower (33% versus 18% recurrence with 21 months minimum follow-up; p < 0.05). The prognostic value of preoperative CEA was apparent only in patients with Dukes' C1 colon tumors. Preoperative CEA values were not of prognostic significance among the rectal adenocarcinoma patients. Although elevated levels of CEA after resection of either colon or rectum cancers were strongly associated with subsequent tumor recurrence, no single CEA value, arbitrarily defined as "elevated", provided an adequate screening test with both high sensitivity and high specificity. Postoperative CEA elevations were more strongly predictive of recurrence when part of a steadily rising trend. In the colon cancer study, the median monthly increase in CEA for disease-free patients was estimated to be zero, and for the relapsed patients 5.8%. The corresponding estimates for patients on the rectal cancer protocol were zero and 7.8%. Only 36 of the 344 disease-free patients on the colon protocol and 14 of the 94 disease-free patients on the rectal protocol (15%) exhibited a rate of increase of CEA as high as 3% per month over the entire period of observation. Two thirds of the relapsed patients on both studies showed a rate of increase this high or higher. The patterns of CEA rise in individual patients were quite varied, however, and monthly rates of increase as established in our study are not to be used as guidelines in patient management.

Carcinoembryonic Antigen↗
PubMed1982

An evaluation of two antigen nonspecific assays for circulating immune complexes using a model system.

Two methods of detecting circulating immune complexes (CIC) in serum, the Protein A-glass fiber filter assay (PA-GFF) and the polyethylene glycol (PEG) insolubilization assay, were compared using a model system of BSA/anti-BSA. Supernatants of the quantitative precipitin curve from extreme antigen excess through antibody excess were tested by both methods. The PEG assay detected soluble CIC in all areas where expected by comparison with the Farr Test; the filter assay did not, although it did detect aggregated globulins quantitatively. The PEG assay detected high levels of CIC in serum of rheumatoid arthritis patients and low levels in normal human serum. Postprandial samples and plasma with heparin or EDTA caused unpredictable increases in results in the PEG assay so that for best results the PEG assay should be run on serum from fasting individuals. PEG insolubilized complexes were analyzed and found to contain expected serum components. A slight modification of the original method was made and tested using two other model complex systems and known CIC-containing sera. The PEG turbidity assay it fast, easy, reproducible, and suitable for quantitating and isolating immune complexes in serum.

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

Potentiation of dimethylhydrazine bowel carcinogenesis in rats.

An animal model of organ-specific chemical carcinogenesis has been used to study environmental effects on the incidence of human colorectal adenocarcinoma. Wistar/Furth weanling rats underwent connection of their urinary and fecal streams (ureterosigmoidostomy), connection of their urinary and fecal streams with proximal fecal diversion (rectal bladder), or sham operations. Age-matched, unoperated control and operated animals then received either no carcinogen, 1,2-dimethylhydrazine (DMH) 20 mg/kg body weight, s.c. once weekly for 16 weeks, N-[4-(5-nitro-2-furyl)-2-thiazolylformamide (FANFT) 0.2% of the feed for 16 weeks, or DMH + FANFT concurrently. Thirty-three weeks after carcinogen exposure, surviving animals were killed and examined for bowel and urinary bladder tumors. The incidence of adenocarcinoma of the colon adjacent to the junction between bladder and bowel was significantly higher in animals after ureterosigmoidostomy compared with animals whose fecal stream had been proximally diverted (14/22 vs. 0/34, P less than 0.001). This effect was not dependent upon chemical carcinogen exposure. Nonexposed animals still developed a significantly higher incidence of colon adenocarcinomas adjacent to their bladder-bowel junctions as compared with animals with proximal fecal diversion (5/8 vs. 0/13, P less than 0.01). In unoperated or sham operated animals, adenocarcinomas of the bowel occurred in 33% of DMH-treated animals and transitional cell carcinomas of the urinary bladder in 33% of the FANFT-treated animals. After concurrent exposure to both carcinogens, no increased incidence of bladder tumors was noted when compared with FANFT treatment alone. However, the number of animals with one or more adenocarcinomas of the bowel (22/30 vs. 17/50, P less than 0.001), the mean number of tumors per animal (2.1 +/- 0.2 vs. 1.1 +/- 0.1, P less than 0.01), and the invasiveness of the tumors were all increased after DMH + FANFT as compared with DMH exposure alone. The carcinogenic potential of direct bladder to bowel connection with intact fecal and urinary streams, and the potentiation by FANFT of DMH-induced colon carcinogenesis may have implications in the genesis of human colorectal cancer.

1,2-Dimethylhydrazine↗
PubMed1981

Results of xenogeneic I-RNA therapy in patients with metastatic renal cell carcinoma.

Six patients with metastatic renal cell carcinoma were treated with five intravenous infusions (every other day) of autologous lymphocytes incubated in vitro with I-RNA extracted from the lymphoid tissue of guinea pigs immunized with the patient's own tumor. No toxicity was evident. One patient showed regression of multiple pulmonary metastases beginning three months after therapy with complete remission by six months. She remained without evidence of disease until 18 months after therapy. Two other patients had more than 50% regression of measurable metastases lasting eight and ten months after therapy. Two patients showed stabilization of previously growing renal cell carcinoma pulmonary metastases. A single patient with renal cell carcinoma metastatic to brain had progressive tumor growth after a single I-RNA treatment. Serial peripheral blood lymphocyte samples obtained from each of the patients during I-RNA therapy demonstrated progressive increase in in vitro cytolysis of allogeneic renal cell carcinoma targets. Boosts in cytolytic effect were shown in all patients during I-RNA treatment regardless of their subsequent clinical course. These results seem to justify a randomized, prospective trial of xenogeneic I-RNA therapy in renal cell carcinoma patients with lesser tumor burden.

Animals↗
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↗