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Biomedical subjects

E Pihl

Publications and source records attributed to E Pihl.

At least 37 records · Page 2Linked to original sources

Altered blood lymphocyte subclasses in patients with ulcerative colitis.

Peripheral blood lymphocytes were studied by flow cytofluorimetry and monoclonal antibody techniques in 107 patients with ulcerative colitis and in 20 healthy controls of similar ages. Total T, T helper (TH), and T cytotoxic/suppressor (TC/S) lymphocytes were defined by the monoclonal antibodies OKT3, OKT4 and OKT8, respectively, while B lymphocytes were defined by surface immunoglobulin. Patients had a significantly (P less than 0.05) lower proportion of TC/S lymphocytes than the controls, and patients with quiescent disease had a reduced proportion of B lymphocytes compared to controls and those with active disease. Patients with marked mucosal dysplasia had a significantly (P less than 0.025) lower proportion of TH lymphocytes and a higher (P less than 0.01) proportion of B lymphocytes than those without dysplasia. There were no significant associations between lymphocyte levels and any other clinicopathological features assessed.

Adult↗

Lymphocyte subclasses in pregnancy induced hypertension.

Peripheral blood lymphocyte subclasses were studied by flow cytofluorimetry and monoclonal antibodies in 21 women with Pregnancy Induced Hypertension (PIH), 20 healthy women in their third trimester of pregnancy and in 20 nulliparous, nonpregnant women. The cells were stained with the monoclonal antibodies OKT3, OKT4 and OKT8 to define total T cells, T helper cells (Th) and T suppressor-cytotoxic cells (Ts/c) respectively. B lymphocytes were defined by their surface immunoglobulin. Absolute numbers of total T cells and Ts/c cells were significantly decreased (p less than 0.05) in patients with PIH compared to either control group. The proportion of B lymphocytes was significantly (p less than 0.01) increased and absolute numbers were marginally increased. These findings reflect an immune disturbance which may be of prime importance in the pathogenesis of this disease.

Adolescent↗

Significance of lymphocyte fluorescence polarization changes after phytohemagglutinin stimulation in cancer and noncancer conditions.

The double-zone fluorescein fluorescence polarization (FFP) "cancer" test was used to study 540 blood lymphocyte samples from 341 donors, of whom 158 had confirmed cancer: The other donors were noncancer patients, pregnant women, and normal individuals. The FFP response in cancer patients was the reverse of that in normal individuals, but an abnormal response was also obtained in some noncancer conditions, including the chronic inflammatory disorders--rheumatoid arthritis, cholecystitis, and diverticulitis--and in early pregnancy or pregnancy-induced hypertension. Thus the cancer discriminatory value of the test is limited. Examination of its biologic basis suggests that the positive FFP response in cancer and other conditions is due to altered immune status of blood lymphocytes, with associated change in cytoplasmic fluidity affecting the polarization of fluorescence. Incubation of normal blood lymphocytes with cyclic GMP induced an abnormal, cancer-like FFP response.

Cyclic AMP↗

High-fat diet promotes and causes distal shift of experimental rat colonic cancer--beer and alcohol do not.

Intestinal cancer was induced in inbred male D/A rats by 1,2-dimethylhydrazine, and the interrelationships between a high-fat (33.5% w/w) diet, beer and alcohol (4.8% v/v) ingestion, and tumor location and incidence were examined. The number of tumors per animal was significantly greater in both the small and large intestines of rats on the high-fat diet, as opposed to the standard diet. The 6-fold increase in incidence of colorectal cancer occurred almost exclusively in the distal half of the large bowel; i.e., there was a highly significant (p less than 0.005) shift, similar to that seen in man in countries adopting high-fat Western-type diets. Neither alcohol nor beer ingestion affected the incidence of intestinal cancers, but beer was associated with a more distal distribution of small-intestinal cancers in animals on the high-fat diet. However, this was not considered sufficient evidence for any material effect of beer on experimental intestinal carcinogenesis.

1,2-Dimethylhydrazine↗

Metastatic 'early' colorectal cancer.

If colorectal carcinomas where the primary tumours are confined to the wall are considered 'early', the likelihood of lymph node metastasis in these tumours is 21% and for those that do not extend beyond the submucosa it is 13%. Because of the renewed interest in local treatment of small accessible rectal tumours and the use of colonoscopy for the removal of 'polyps' with invasive carcinoma, we analysed our long-term cancer survival figures for 'early' cancers in this combined surgical series spanning more than 30 years. The presence of regional lymph node metastasis in 'early' rectal cancer was associated with a significantly (P = 0.001) reduced proportion of long-term survivors (56%) compared to those without nodal involvement (79%). Long term survival in 'early' colonic cancer was less influenced (P less than 0.05) by whether lymph node metastasis was present (73%) or not (77%). The authors conclude that until more information is available with regard to the risk of lymph node spread from 'early' tumours, resection is advised for all invasive tumours of the colon in good risk patients, but the indications for local excision of 'early' rectal cancers can be extended in view of the ease of careful follow-up and the use of salvage procedures in those with recurrence.

Colonic Neoplasms↗

Antibody-dependent cellular cytotoxicity (ADCC) in colorectal carcinoma. I. Favorable prognosis in female patients.

In an immunological study of 288 colorectal carcinoma patients, we investigated the relationship between survival and preoperative in vitro antibody-dependent cellular cytotoxicity (ADCC) against the colonic carcinoma cell line HT-29. A highly significantly favorable (p = 0.001) association was found in the 20 female patients with ADCC. Nearly all (97%) of the 66 patients with ADCC were blood group O, but blood group per se did not relate to survival, nor could staging explain the survival association with ADCC. The mechanism whereby ADCC or its in vivo expression confers a survival advantage is unknown but we suggest that it derives from immunoreactivity against blood group A antigens produced inappropriately in the carcinomatous epithelium of the group O and B patients.

ABO Blood-Group System↗

Antibody-dependent cellular cytotoxicity (ADCC) in colorectal carcinoma. II. Blood group association.

Colorectal carcinoma patients' sera with ADCC antibody reacting with the HT-29 cell line (blood group A) generally (88%) cross-reacted with another group A cell line (COLO-394) but much less frequently (6-33%), with six tumor cell lines that did not express ABO blood group antigens. The findings suggested the possibility that the ADCC reactivity against the HT-29 cell line particularly by patients of blood group O is generally via "A" or "A-like" antigenicity of the target cells. This was supported by absorption studies that showed that the ADCC reactivity could be removed by blood group A but never by group B erythrocytes. Our results suggest that the prognostically favorable ADCC antibody in colorectal carcinoma patients' sera is of anti-blood group A specificity or cross reactivity.

ABO Blood-Group System↗

Mucosal dysplasia. A major predictor of cancer following ileorectal anastomosis.

Fifty patients with ulcerative colitis managed by colectomy and ileorectal anastomosis had rectal biopsies performed in the period 1967 to 1972. Follow-up information was available on all patients. Thirty-nine patients were reviewed and rectal biopsies performed in the 1980 to 1982 period. Three patients had developed rectal cancer in the period 1975 to 1980, and two rectal cancers were detected in the 1980 to 1982 follow-up period. All cancers occurred in patients with a diagnosis of moderate or severe dysplasia in biopsy specimens from the 1969 to 1972 period. The probability of developing rectal cancer after a diagnosis of moderate or severe dysplasia in this series reached 42 per cent at nine years from diagnosis.

Adult↗

T helper lymphocyte depression in early human pregnancy.

Peripheral blood lymphocyte subclasses were determined in 60 women with normal pregnancies, 20 from each trimester, and in 20 controls using automated flow cytofluorimetry. The cells were stained with the monoclonal antibodies OKT3, OKT4 and OKT8 to stain total T cells, T helper and T suppressor-cytotoxic lymphocytes, respectively. A polyvalent rabbit anti-human Ig serum was used to stain B lymphocytes. Absolute numbers of T lymphocytes were significantly reduced in both the first and second trimesters. This was due to a significant decrease in T helper lymphocytes and a smaller, statistically not significant, reduction in the number of T suppressor lymphocytes. There was no significant change in lymphocyte subclasses during the third trimester. Total lymphocyte numbers were normal throughout pregnancy.

Antibodies, Monoclonal↗

Monoclonal antibodies to human colon and colorectal carcinoma.

A series of monoclonal antibodies was produced by immunizing mice with fresh carcinoma of the colon and with the cell line HT-29. These antibodies could be classified into 3 different groups: (a) those which were HT-29 specific and reacted with no other cell line or fresh colon carcinoma samples; (b) antibodies which reacted with HT-29 and were also reactive with a number of other in vitro cell lines; and (c) antibodies which appeared to be specific for carcinoma of the colon cell lines in that they reacted selectively with colon carcinoma cell lines and not with carcinoma lines derived from other tissues. It was clearly shown by immunoperoxidase staining of both normal and neoplastic cells of the gastrointestinal mucosa, from stomach to colon, that these antibodies were not tumour-specific. Indeed, one antibody (250-30.6) has a remarkable specificity for secretory epithelium of any tissue whether it be found in the gastrointestinal tract, respiratory system or urinary system. We question the existence of tumour-specific antigens detected by monoclonal antisera described thus far, and comment on the remarkable specificity of some of the sera produced, emphasized by the secretory cell-specific antibody described herein.

Animals↗

Immunoglobulins intrinsic to colorectal carcinoma: an unfavorable prognostic association with IgM.

Immunoglobulin (Ig) eluates prepared from cell membrane fractions of 50 colorectal carcinomas were found to contain significantly (P less than .001) less IgA and IgM and marginally less IgG than normal colon mucosa. IgA and IgG were present in all tumors, but IgM was present in only 20 of 50 tumors (40%). Small (less than or equal to the median vol) tumors contained significantly (P less than .05) more IgA and IgG per gram tissue than did large tumors. Tumors with a large (greater than the median) proportion of stroma contained more IgG than did those with less stroma. No associations were found between Ig and amount of viable-appearing tumor tissue, necrosis, mucin production, and staging. Patients whose tumors contained measurable amounts of IgM had a significantly (P = .012) shorter survival than did patients without intrinsic IgM (12 and 27 mo at the 75th percentile, respectively). The difference could not be explained by conventional staging.

Adenocarcinoma↗

Germinal centre hyperplasia: an unfavourable immune response in recurrent malignant melanoma.

A quantitative immunomorphological analysis of actively responding B-(germinal centre) and T-lymphocyte (paracortical) areas in 187 patients with malignant melanoma recurrent in the regional lymph nodes has been made. The results show that tumour involved nodes have significantly increased germinal centre and decreased paracortical response in comparison with uninvolved lymph nodes. Patients treated with surgery alone whose uninvolved nodes had hyperplastic (defined as exceeding the median) germinal centre areas, had significantly shorter survival than those without germinal centre hyperplasia. No association was found between lymph node immunomorphology and survival in BCG treated patients.

BCG Vaccine↗

Persistence of organ- and iso-antigens in vitro in a long-term culture cell line of colonic carcinoma.

Cells of colonic carcinoma line HT-29, cultured over more than 170 generations and extensively used in immunological studies of patients with colorectal tumours, still express several immunologically valuable characteristics presumably present since its inception. The cell line can induce a poorly differentiated adenocarcinoma in the nude mouse, it has human antigenic characteristics, it expresses blood group A antigen, and produces a colon-specific mucin and CEA, though not colon cancer-specific mucin (CCM). It remains useful as a target for in vitro testing of anti-tumour immunoreactivity in colorectal cancer patients.

Adenocarcinoma↗

Lymphocyte fluorescence polarization changes after phytohemagglutinin stimulation in the diagnosis of colorectal carcinoma.

A lymphocyte fluorescence polarization test that measures reactivity to phytohemagglutinin (PHA) has permitted discrimination of a majority of patients with colorectal carcinoma from noncancer individuals. The test involves separation of two lymphocyte fractions from 20 ml venous blood on a modified leukocyte separation gradient, incubation with PHA for 45 minutes, addition of fluorescein diacetate, and analysis of change in fluorescence polarization. Of 19 colorectal patients tested preoperatively, 13 had a positive stimulation index, 3 a zero index, and 3 a negative index. Of 7 patients with other malignant neoplasms, a positive value was obtained in 6 and a negative value in 1. Of 14 patients with other diseases, a negative value was obtained in 9, zero in 3, and positive in 2. Of 31 normal donors a negative value was obtained in 27, zero in 2, and weak positive in 2. This rapid test promises to develop into a useful cancer-diagnostic method, and elucidation of its biological basis should identify a new cancer marker.

Adult↗

Preserving the ascending colon as an alternative surgical option in ulcerative colitis.

Six patients with ulcerative colitis were studied to assess the histologic appearance of the ascending colon which was preserved at the initial operation performed more than ten years previous. Inflammatory cells were increased in all patients, but ulceration was not present microscopically. Most patients had less than five bowel movements a day. Because of good long term survival of the mucosa, wider use of a surgical approach is proposed, based upon excising the colonic mucosa most prone to ulceration and metabolic derangement. The procedure entails subtotal colectomy, mucosectomy of the rectal mucosa and preservation of the ascending colon as a neorectum. Prime advantages are the lack of a stoma and fewer bowel movements than result from other operations.

Adult↗

Long term results of restorative resection and total excision for carcinoma of the middle third of the rectum.

Restorative resection for carcinoma of the middle third of the rectum has been facilitated by the recent introduction of the staplers. Before restorative resection with end-to-end anastomosis can become the treatment of choice, it must be proved that survival prospects after restorative resection are similar to those obtained after total abdominoperineal excision. The results of curative restorative resection and total excision in 417 patients with a single carcinoma of the middle third of the rectum managed by one of us are examined. Between 1950 and 1980, the proportion of patients treated by restorative resection for carcinoma of the middle third of the rectum increased from 26 to 93 per cent. Distribution by sex, age, tumor stage and tumor differentiation did not differ significantly between the two groups of patients operated upon. Cancer specific survival did not differ significantly between patients treated by restorative resection or total excision. Ten year survival rates were 60 and 59 per cent, respectively. Survival related to tumor stage and differentiation was not influenced by the type of operation. Tumor size, greater--p less than 0.04--in patients managed by total excision, had no significant influence on survival prospects. The results justify sphincter preservation and suggest that increased usage of restorative resection by stapling technique is not likely to lessen survival prospects in patients with carcinoma of the middle third of the rectum.

Adenocarcinoma↗