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Biomedical subjects

R H Whitehead

Publications and source records attributed to R H Whitehead.

At least 91 records · Page 5Linked to original sources

Significance of tumour mass on T-lymphocyte levels in patients with gastrointestinal cancer.

The relationship between tumour load and immunity in gastrointestinal cancer has been studied by sequential comparison in patients whose tumour has been removed and those whose tumour was found to be inoperable. Total lymphocyte count, absolute and percentage T- and B-lymphocyte counts, effect of papain on E-rosetting cell levels, and inhibitory effect of cancer sera on E-rosette formation by normal lymphocytes have been studied in 30 patients with stomach or colorectal cancer, and 10 control patients with benign gastrointestinal disease. The examination was done on each patient before and at regular intervals after operation up to 24 weeks. Operable cases, with removal of tumour load, showed a temporary fall in total lymphocyte count and T cell counts, which returned to normal by four weeks postoperatively. Inoperable cases (15 patients) showed a progressive fall in total lymphocyte count and a relatively greater depression of T cell counts, in parallel with increasing tumour mass. E-receptor blocking factor was demonstrated in the sera of cancer patients. This factor was related to tumour mass and presumably was of tumour origin, as it persisted in the inoperable group but disappeared by 12 weeks after tumour removal. The factor explained the excess depresion of T cells over total lymphocytes, but does not explain the continuing depression of total lymphocyte count in the cancer patients.

Aged↗

Importance of methodology in demonstrating depression of T-lymphocyte levels.

A comparison has been made of 3 methods of determining E rosettes in young, healthy people, women with breast cancer and an age-matched group of healthy women, in an attempt to explain the wide variations in T-cell levels in different disease states reported by different workers. The greatest difference in levels of E-rosetting cells between the different groups was seen in incubation of 1 1/2 h at 4 degrees C. Much of the difference seen in these comparisons disappeared after overnight incubation at 4 degrees C, which was associated with an increased T-cell level in all groups. Consequently, although maximal levels of T lymphocytes as determined by E rosetting are found using overnight incubation, a short incubation period may be superior for demonstrating subtle depressions in levels of T lymphocytes as seen in elderly people and cancer patients. This depression is not considered to be cancer specific, because of the findings in the age-matched control group and similar findings in benign disease states.

Adult↗

The macrophage electrophoretic mobility (MEM) test--an investigation of its value as a routine laboratory test in the detection of malignant disease.

A previous study of the MOD-MEM test showed promising results. We have attempted to repeat the study using a blind coded series of 210 blood samples from normal subjects and patients with either benign or malignant disease. Using standard criteria the false negative rate for cancer patients averaged 43% and the false positive rate for non-cancer patients averaged 34%. The results indicate that the test at the present time, under routine laboratory conditions, is not reliably reproducible and does not have the ability to effectively discriminate between benign and malignant disease. It is suggested that blind coded studies be used more frequently in assessment of tests with cancer detection potential.

Antigens↗

Distribution of 5-fluorouracil to body tissues compared after intraluminal, intravenous, and intramural administration in gastrointestinal cancer.

The distribution of 5-fluorouracil (5-FU) to various potential metastatic sites has been investigated in stomach and colorectal cancer patients, using intraluminal, intravenous, and intramural routes of administration at the time of surgery. The best overall concentrations of 5-FU in systemic blood, portal blood, liver, draining lymph nodes, tumor, and locally in the bowel wall was obtained after intramural injection. The intraluminal route of administration resulted in poor overall distribution of 5-FU. Intravenous administration tended to give levels between those obtained from intramural and intraluminal routes. There was no complication of 5-FU therapy. On the basis of this study we conclude that the intramural route is the most satisfactory for adjuvant administration of 5-FU with surgery. This might be expected to give better results than those obtained in clinical studies using intraluminal and intravenous routes. A controlled trial of 5-FU using the intramural route is indicated in gastric and colorectal cancer to demonstrate whether or not clinical benefit can be obtained.

Aged↗

Masking of receptors for sheep erythrocytes on human T-lymphocytes by sera from breast cancer patients.

Sera from 140 breast cancer patients and 38 controls were tested for their ability to inhibit sheep erythrocyte (E) rosette formation by normal, allogeneic lymphocytes. Inhibition of rosette formation by greater than 20% was found with 65% of stage I sera, 91% of stage II sera, 56% of stage III sera, and all stage IV sera. In contrast, only 13% of control sera was inhibitory. The inhibitory factor was found to bind to only a proportion of T-lymphocytes and could be removed from these lymphocytes by mild proteolytic digestion or extended washing. Examination of the properties of the inhibitory factor indicated that it differed from other substances that reportedly inhibited E-rosette formation.

Binding Sites↗

The effects of splenectomy, mesenteric lymphadenectomy and portacaval shunt on antibody responses to antigens within the small intestine.

The primary and secondary systemic antibody responses to protein antigens introduced into the gut (diphtheria toxoid, lauroylated human serum albumin) were not diminished or enhanced by previous splenectomy, mesenteric lymphadenectomy or portacaval shunt. Immunization with diphtheria toxoid before such operations did not produce significant alterations in the responses. The cells forming antibody were found predominantly in the lamina propria of the small bowel and to a lesser extent in the subcapsular sinuses of the mesenteric lymph nodes when tissues were examined by the fluorescent antibody technique, ten days after the secondary stimulus of intestinal diphtheria toxoid. The experiments show that the responses, stimulated locally by gut absorbed protein are little affected by an altered portal circulation.

Animals↗

T and B lymphocytes in breast cancer stage relationship and abrogation of T-lymphocyte depression by enzyme treatment in vitro.

B and T lymphocytes have been measured in 100 women--71 patients with breast cancer and 29 controls--using sheep-erythrocyte rosetting techniques. Compared with controls (healthy women or patients with benign breast disease), there is a highly significant depression of T-cell percentage in all stages of breast cancer except locally advanced (stage 3) disease. These stage-3 cases seem to constitute a biologically distinct group. T-cell percentages in early (stage 1) patients overlap with those seen in stages 3 and 4, raising the possibility that there are in stage 1 two subpopulations of T-cell values that are associated with differences in subsequent tumour progression. B-lymphocyte levels are similar in all groups. Low T-cell levels return to normal after incubation with papain in virto but fall again after resuspending the treated lymphocytes in autologous (cancer) serum. The results suggest that T-cell depression is due to a masking factor on the surface of some T lymphocytes which is also present in the serum of cancer patients, and removable by enzyme digestion.

Adult↗

Inhibition of K cell function by human breast cancer sera.

Sera from breast cancer patients and from female controls were tested for inhibition of lysis of antibody-coated target cells by human leukocytes (K cells). Sera from 39% of breast cancer patients, but from only 8% of controls, inhibited lysis by more than 30%. This inhibition was unrelated to the stage of the disease, the patient's age or whether the patient was pre- or post-operative. Inhibition was apparently not due to anti-HLA antibodies and did not correlate with the IgG level or anti-complementary activity of the serum. On fractionation by gel-filtration, inhibitory activity was found in fractions of higher molecular weight than IgG. As no IgG could be detected in these fractions, inhibition is probably not due to immune complexes containing IgG antibody. The inhibitory factor may well contribute to the immunosuppressed status of a proportion of breast cancer patients.

Adult↗