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Biomedical subjects

E D Holyoke

Publications and source records attributed to E D Holyoke.

At least 55 records · Page 3Linked to original sources
PubMed1978

Pre- and postoperative uses of CEA.

CEA plasma levels obtained prior to definitive surgery in patients with colorectal cancer in our hands have predictive ability. An elevated CEA greater than 2.5 ng/ml recorded by our laboratory means an increased risk of subsequent local recurrence or of later metastatic disease. The question as to whether or not this is additive as a prognostic variable when tested against careful histopathological staging remains. As a monitor, CEA will detect recurrence. Again, the problem as to how accurate this is remains. If we use two consecutive elevations of plasma CEA greater than 2.5 ng/ml as a criteria, we encounter about 15% false positives which must be weighed against finding disease significantly earlier in about one-third of the patients followed. Our data for second-look procedures indicate clearly that when used in patients with an elevated CEA laparotomy may be useful and further studies showed the presence of disease in 11 of 14 patients with an elevation following surgery for two consecutive tests were greater than 2.5 ng/ml. Two were operable. The significance of these findings is described.

Carcinoembryonic Antigen↗
PubMed1978

Identification of a macromolecule containing an anticarcinoembryonic antigen-reactive substance and immunoglobulin M in human pancreatic cancer.

Ascitic fluid from a patient with carcinoma of the pancreas was fractionated by ammonium sulfate precipitation. The fraction precipitated between 25 and 50% saturation of ammonium sulfate was sequentially chromatographed on Sephadex G-200 and Sepharose 6B. A macromolecular fraction (greater than 10(6) daltons) obtained was found to react with both antihuman IgM and antiserum to carcinoembryonic antigen (CEA). This fraction was further purified by adsorption with protein A-Sepharose CL-4B and chromatography on DEAE-Sephacel. The purified macromolecular fraction had a sedimentation value of 28S as determined by ultracentrifugation. Upon dissociation of the purified macromolecule at pH 2.3 and purification of the dissociated components on Sepharose CL-2B and BioGel A 1.5M, a 19S protein and a 5S protein were recovered. The 19S protein showed a complete line of identity with a reference human IgM when reacted with antihuman IgM in gel diffusion, whereas the 5S protein showed a partial immunologic identity with colon CEA against anti-CEA. These results indicated the existence of an IgM-containing macromolecular complex with an anti-CEA cross-reactive substance in the extracellular fluid of human pancreatic cancer.

Ammonium Sulfate↗
PubMed1978

Elemental diet as an adjuvant for patients with locally advanced gastrointestinal cancer receiving radiation therapy: a prospectively randomized study.

Thirty patients with locally advanced, nonresectable, nonmetastatic cancer in the peripancreatic region, stomach and colorectum-anus, to be treated with radiation therapy with or without adjuvant chemotherapy, were randomized to receive standard diet and either usual between-meal feedings or 300 calories tid of a high nitrogen elemental diet. Although weight loss associated with radiation therapy was not significantly reduced in those receiving the nutritional supplement, delayed hypersensitivity skin test responses tended to improve in patients receiving the elemental dietary supplement and to deteriorate in controls. Planned radiation therapy was completed in all nutritionally supported patients. One control patient expired shortly after treatment was halted abruptly, and three other control patients required rescue by total parenteral nutrition.

Energy Intake↗
PubMed1978

Peritoneolysis in the reconstruction of the Roux-en-Y loop.

A technique to provide an additional 5 centimeters of length, without compromising the blood supply to the anastomosis, was developed. It has been applied to 26 patients, 18 with Roux-en-Y biliary bypass at various levels, five with high Roux-en-Y esophagojejunostomies and three with gastrojejunostomies. In the last three patients with unresectable adenocarcinoma of the distal part of the stomach and invasion of the intestinal mesentery, due to foreshortening of the latter, the proximal loop of the intestine would not reach the desired level of the stomach until this maneuver was performed.

Adenocarcinoma↗
PubMed1978

Estramustine phosphate in the treatment of advanced malignant melanoma.

Twenty-six patients (14 men and 12 women) with histologically proven advanced malignant melanoma, who previously had not responded to DTIC, methyl-CCNU, and procarbazine, received estramustine phosphate (estracyt) (15 mg/m2) in daily divided doses. All patients had measurable disease. One patient developed a complete remission and one patient had improvement in liver function without measurable regression in the tumor. In three other patients (11%), the disease remained static for a period of 3--5 months. The mean survival time from the beginning of therapy was 16.8 months for the patients with a response or static disease and 2.18 months for those who had no response. Gastrointestinal toxicity was minimal; no hematologic toxicity was observed. It appears that estramustine phosphate used as a single agent for treating advanced malignant melanoma after patients failed to respond to DTIC and to the combination of methyl-CCNU and procarbazine has a poor response rate.

Adult↗
PubMed1978

Micro-leukocyte adherence inhibition. I. Cellular basis of the mechanism of reactivity.

To study the cellular basis for specific antigen-induced leukocyte adherence inhibition, enriched populations of B cells, T cells, and monocytes were prepared by a two-stage adherence separation procedure from spleen cells of normal C57BL/6J mice and mice bearing progressively growing MCA-38 tumors. The reactor cell undergoing specific antigen-induced adherence inhibition was identified as a monocyte (esterase positive, did not respond to mitogens, and did not bear Thy 1.2 antigen or surface immunoglobulin). Furthermore, an enriched population of MCA-38 sensitized B cells could program normal monocytes to undergo specific antigen-induced adherence inhibition. This programming could be abolished by pretreatment of the MCA-38 sensitized B cells with anti-immunoglobulin and complement (indirect cytotoxicity method). In contrast, enriched populations of MCA-38 sensitized T cells could not program normal nylon wool adherent cells to undergo antigen-specific adherence inhibition; and anti-Thy 1.2 serum and complement had no effect on specific antigen-induced adherence inhibition. Thus, in this murine tumor model, leukocyte adherence inhibition appears to be due to the programming of monocytes by sensitized B cells.

Adenocarcinoma↗
PubMed1977

Impaired lymphocyte blastogenic response in patients with colon adenocarcinoma: effects of disease and age.

The in vitro blastogenic response of 76 patients with colon adenocarcinoma and 29 age-matched normal healthy volunteers was compared. An age-related decline in cellular immunocompetence was observed in both the patient and control group. Within each age interval, the patients' blastogenic responses were lower than the controls' and the rate of decline of the blastogenic response in the patient group was greater in magnitude, suggesting that their disease state also contributed to loss of cellular immunocompetence. Thus, both increasing age and presence of tumor are factors that contribute to the decline the immunocompetence in patients with colon adenocarcinoma.

Adenocarcinoma↗
PubMed1977

Age-related impairment of tumor-associated lymphocytotoxicity in patients with colonic adenocarcinoma.

The in-vitro lymphocytotoxic responses of 27 preoperative colonic-carcinoma patients and 61 healthy volunteers were correlated with age by linear regression analysis. Cytotoxicity obtained with leukocytes from the colonic-cancer patients on the colonic cancer cell line decreased with increasing age. In contrast, cytotoxicity obtained with leukocytes from the control group on the same cell line did not correlate with age of the donor. Furthermore, the decline in cytolysis in the patient group could not be attributed to more extensive disease. These observations suggest that increasing age is an important factor associated with the decline in ability of colorectal cancer patients to generate a disease-related cytolytic reaction.

Adenocarcinoma↗
PubMed1977

Leukocyte adherence inhibition: an automated microassay demonstrating specific antigen recognition and blocking activity in two murine tumor systems.

This communication describes an automated micro-adherence inhibition assay. Tumor-specific immunity was demonstrated with B16 melanoma and MCA-38 colon adenocarcinoma, both of which are syngeneic to the same strain of mouse (C57B16/J). Abrogation of the leukocyte adherence inhibition (LAI) response of sensitized leukocytes has been demonstrated in the MCA-38 tumor system by the addition of serum from mice bearing MCA-38 progressively growing tumors, a property not present in normal serum. The sensitivity of the system has also been demonstrated by showing that LAI will change prior to a tumor becoming palpable. This microassay has the advantage of being simple, rapid and reproducible, and involves the use of minimal quantities of antigenic preparations and leukocytes, and in addition is amenable to rigorous statistical analysis.

Adenocarcinoma↗
PubMed1977

Isolation of human peripheral blood lymphocytes: modification of a double discontinuous density gradient of Ficoll-Hypaque.

Incubation of whole blood with adenosine diphosphate (ADP) and carbonyl iron prior to layering on a double discontinuous gradient of Ficoll-Hypaque selectively reduced the number of platelets and monocytes found at the upper lymphocyte interface after centrifugation. This modification in combination with a double discontinuous gradient results in a lymphocyte isolation method that is simple, rapid and reproducible.

Cell Separation↗
PubMed1977

Murine colon adenocarcinoma: syngeneic orthotopic transplantation and subsequent hepatic metastases.

Syngeneic murine colon adenocarcinoma (MCA-38) cells were transplanted in the submucosa of distal colon, proximal colon, cecum, ileum, jejunum, and duodenum of male C57BL/6 mice, with local lymphoid follicles used as points of entry. The tumor grew best at the cecum and led to liver and mesenteric lymph node metastases in 8 and 9 weeks, respectively, after transplantation. Histologically, a local inflammatory reaction involving polymorphonuclear leukocytes was observed within 48-72 hours following transplantation; after this time, the microscopic tumor foci began to grow progressively. Mononuclear lymphoid cells of the gut-associated lymphoid tissue did not infiltrate the progressively growing tumor; however, polymorphonuclear leukocytes were constantly observed at the tumor periphery in the lamina propria. The studies indicated that orthotopic transplantation as a model system can provide a means of examining the role of the local immune response as a focus of host resistance and as a factor in metastatic tumor spread. The findings also suggested the usefulness of this model in immunotherapeutic and chemotherapeutic studies of secondary hepatic disease.

Adenocarcinoma↗
PubMed1977

CEA monitoring of palliative treatment for colorectal carcinoma.

Palliative treatment was applied to 131 cases of unresectable or palliatively resected colorectal carcinoma being monitored with serial CEA determinations. There were 84 instances of disease progression with 67 (80%) of them showing an increase in CEA above pretreatment levels or maintaining high levels, and 17 (20%) showing a fall when compared to pretreatment values or maintaining low initial values. There was a clear-cut regression of the disease in only 9 instances. In all 9, the CEA clearly dropped or maintained low valles throughout the period of regression. No patient in regression had a rise or maintained an elevated CEA level. These changes in CEA followed closely the clinical response of our patient to the use of a particular agent, although for the Nitrosourea compounds there may be a tendency to lower the CEA regardless of the patient's tumor response to the drug. This could be due to the fact that the Nitrosoureas produce a diffuse block of cellular activity, both at the nucleous and cytoplasm; while other compounds act as alkylating agents or by inhibition of enzymes involved in the metabolism of nucleic acids (i.e., 5-FU inhibiting thymidylate synthetase). In general, longer survival was found in those patients who had initially lower levels of CEA as compared to those with high initial levels. The patients with a favorable CEA response to the treatment (falling CEA or maintained low value), even in many who did not show a clinical response had a longer survival than the group with rising or stable high levels. The main value in CEA monitoring of patients resides in its correlation with the amount of disease present and then its ability to detect progression of tumor mass which is not clinically measurable.

Adult↗