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Biomedical subjects

C H Thompson

Publications and source records attributed to C H Thompson.

At least 109 records · Page 6Linked to original sources
PubMed1989

Monoclonal antibodies reactive with mucin expressed in breast cancer.

Three murine monoclonal antibodies (BC1, BC2 and BC3) were developed against human milk fat globule membrane (HMFGM). By immunoperoxidase staining, it was found that the antigenic determinants had a predominant distribution in breast cancer tissue. In addition, the antibodies reacted preferentially with mucin derived from human milk rather than that derived from the breast cancer cell line ZR75; they also recognized polymorphic high molecular weight components (MW greater than or equal to 230,000) in serum and in human milk fat globule membrane. Thus the antibodies appear to react with a component of the family of mucins found in breast cancer and human milk and it appears likely that at least part of each epitope is protein in nature. Antibodies BC1, BC2 and BC3 recognized related but not identical epitopes, and they appear to be co-expressed on the same molecules as 3E1.2-defined antigen (mammary serum antigen, MSA) which is also a member of the family of breast cancer-related mucin. However, the 3E1.2 epitope is distinct and non-cross-reactive with those described for BC1, BC2 and BC3. The BC2 and BC3 defined epitopes were examined for their value in serum assays. Immunoassay was developed with a combination of two antibodies, using antibody BC3 for antigen capture and antibody BC2 or 3E1.2 for antigen detection and gave reasonable sensitivity (approximately 85%) and specificity (approximately 95%) in such serum tests for breast cancer. In a limited study, these tests appeared to complement the MSA test in the detection of breast cancer.

Antibodies, Monoclonal↗
PubMed1989

Angiodysplasia in patients with renal insufficiency.

Sixty-five patients with angiodysplasia were studied: 42 (64.6%) had normal renal function and 23 (35.4%) had renal insufficiency, defined as serum creatinine consistently greater than 1.5 mg/dl. Comparison of results in the two groups showed that there were no significant differences in the mode of presentation or anatomic distribution of angiodysplasia. Systemic hypertension, congestive cardiac failure, coronary artery disease, and diabetes mellitus were significantly more common in patients with renal failure. Recurrent bleeding from upper alimentary angiodysplasias occurred significantly more often in patients with renal failure than in those with normal renal function. However, a second source, as a cause of bleeding, was found significantly more often in patients with normal renal function.

Aged↗
PubMed1988

Detection of mammary serum antigen in sera from breast cancer patients using monoclonal antibody 3E1.2.

Murine monoclonal antibody 3E1.2, made against human breast cancer cells, detects a glycoprotein (Mr greater than 300,000) called mammary serum antigen (MSA) which is elevated in the serum of patients with breast cancer. An enzyme immunoassay was developed to detect MSA in human serum and used to detect MSA in subjects with breast cancer and other diseases. Raised levels of MSA (greater than 300 inhibition units) were found in the serum of 1.9% of 2406 blood donors, in 18% of sera from 40 subjects with benign breast disease, and in 16% of sera from 222 subjects with non-breast cancers. However, in patients with a diagnosis of breast cancer, 76% (84 of 110) of Stage I and II, and 86% (142 of 166) of Stage III and IV had levels of greater than 300 inhibition units. Nineteen % of patients, classified clinically disease free, had raised MSA levels. In 34 of 37 (92%) patients followed over 2 to 11 mo the level of MSA correlated with the clinical course of disease. Changes in MSA levels not only corresponded to changes in the clinical course of disease, but also preceded the clinical detection of progressive disease. Immunoblotting has detected a heterogeneous molecule of Mr greater than 300,000 and been used to confirm the elevation of MSA in breast cancer patients. Determination of MSA level may be useful for the detection of breast cancer and for monitoring progress of disease and response to therapy.

Antibodies, Monoclonal↗
PubMed1988

Production of monoclonal antibodies to serum antigens in colorectal carcinoma.

Two monoclonal antibodies (mAb) to colorectal cancer were produced using a novel immunization technique. This involved immunizing mice with whole serum obtained from patients with cancer of the colon (three with metastatic disease) and resulted in antibodies which were reactive with colonic tumor tissue by immunoperoxidase testing. Two mAbs (O-1, I-1) were isolated which were non-reactive with normal tissue and with tissues obtained from subjects with benign disease but were reactive with 34/50 (formalin-fixed) colon carcinoma specimens. Further testing on cell lines and other malignant tumors suggested both mAbs detect carcinoembryonic antigen (CEA) as their reactivities were similar to a known anti-CEA antibody, and they reacted with CEA in a solid-phase radioimmunoassay. The two mAbs were found to react with the same or closely associated epitopes on CEA by competitive tests. As the anti-CEA antibodies were made to serum (rather than tissue) CEA, it was possible that unique, highly specific mAb has been produced, particularly as there was a selective reaction of the mAbs for malignant but not normal tissues. A serum test with mAb I-1 was developed which detected raised serum CEA levels in 3/24 patients with benign colonic lesions, 7/19 patients with pancreatic cancer, 5/25 patients with colonic cancer but not in 20 normal individuals. There was direct correlation between these results and a commercially available CEA test kit.

Animals↗
PubMed1988

Papillomavirus and cervical cancer: a clinical and laboratory study.

It is now widely accepted that HPV types 16, 18, 31, and 33 are associated with the development of high grade intraepithelial neoplasia and malignant lesions in the cervix. On this basis, the identification of HPV types in cervical scrape samples has been advocated as a supplement to cytological screening tests. However, little is known of the distribution of the virus at different sites in the lower female genital tract or of how this distribution may change during the natural course of HPV infection. In this survey, HPV DNA dot hybridizations and, in some instances, Southern blot hybridizations with mixed HPV 6/11 and 16/18 probes were undertaken to detect HPV DNA in cervical scrapes and biopsies of the cervix, vagina, and vulva. A total of 92 women attending a Sydney hospital were screened: 59 of these patients had cervical disease, either invasive cervical carcinoma (CaCx) or cervical intraepithelial neoplasia (CIN), grades I-III. A group of 33 women who lacked evidence of cervical abnormalities served as controls. HPV DNA, predominantly type 16/18, was detected in the cervical biopsies of 96% of the CaCx patients, 80% of the CIN III patients, and 65% of the CIN I-II patients. In contrast only 9% of the cervical biopsies from the control group contained detectable HPV 6, 11, 16, or 18 DNA. A high proportion of the women with cervical abnormalities had evidence of concurrent vaginal and/or vulval papillomavirus involvement. The significance of these findings for routine screening and subsequent management of patients with HPV-associated cervical disease is discussed.

Biopsy↗
PubMed1988

Human papillomavirus: the untreated male reservoir.

Human papillomavirus infection currently is accepted as a major factor in the etiology of carcinoma of the cervix, vagina and vulva. While the nature of genital human papillomavirus infection in women is well documented, detailed knowledge of the disease in the male partners is lacking. Therefore, a prospective study was done to define the disease in the genitals of heterosexual men and to formulate an appropriate plan of management. We studied 52 men during an 8-month period for evidence of genital human papillomavirus infection. The majority of the lesions occurred on the shaft of the penis and on the foreskin of uncircumcised men. Deoxyribonucleic acid dot hybridization of biopsies of macroscopic warts and suspected warty lesions with mixed human papillomavirus types 6 and/or 11 and 16 and/or 18 probes revealed that 87 and 55 per cent, respectively, were positive for 1 or more of these human papillomavirus types. Of the macroscopic warts and subclinical lesions 52 and 29 per cent, respectively, contained the more potentially oncogenic types 16 and/or 18, either alone or in combination with types 6 and/or 11. There was no evidence of human papillomavirus in any semen or urine sample but human papillomavirus deoxyribonucleic acid sequences were detected in 31 per cent of the biopsies from apparently normal penile skin and in 18 per cent of the urethral mucosal biopsies. We suggest that management of human papillomavirus infection be directed toward prevention and contact screening, together with ablation of localized lesions.

Acetates↗
PubMed1988

Evaluation of MSA as a serum marker in breast cancer: a comparison with CEA.

In a blind study, 518 serum samples were assayed for serum levels of mammary serum antigen (MSA) by an enzyme immunoassay (EIA) using the 3E1.2 monoclonal antibody. Using 300 IU as the arbitrary cut off to distinguish normal from abnormal individuals, 75% of patients with primary Stage I carcinoma of the breast (n = 12), 89% of those with Stage II (n = 9) and 93% of those with Stage IV (n = 57) had elevated levels of MSA. A relationship was observed between the level of MSA and stage of disease, and therefore with the extent of tumour burden. Levels of MSA were also determined in a series of 19 patients undergoing chemotherapy for breast cancer. Over a 2-24 month period, the change of MSA levels corresponded with the clinical course of the disease in 17 (89%) cases. MSA levels were also raised in some patients with ovarian, colon, lung and kidney cancer, but the average level was lower than in patients with breast cancer. A comparison of CEA and MSA levels in these patients revealed that MSA was a substantially better marker for breast cancer than CEA. The results of this study demonstrate that MSA levels are elevated in patients with breast cancer and may provide a useful means of following the clinical course of patients with this disease.

Antigens, Neoplasm↗
PubMed1988

Hospital mergers and their impact on radiology.

As hospitals enter a new era of competition for patients, changing methods of reimbursement will likely reduce the inpatient volume historically experienced. Because of these and other factors, some hospitals have entered into mergers to remain financially viable. This article examines the causes, benefits and pitfalls of hospital mergers, as well as their impact on radiology departments. A description of the merger of St. Joseph Mercy Hospital and Evangelical Deaconess Hospital into the Samaritan Health Center of Detroit, Michigan is presented along with an overview of the significant impact on the radiology department.

Health Facilities↗
PubMed1987

Transplantation of cultured autologous epidermis to a patient with burns.

Explant-derived cultured autologous epidermis was used as a graft in a 41-year-old female patient with burns, the first subject in a clinical trial of the technique. A small full-thickness biopsy specimen which was taken on Day 2 of the hospital admission was used to initiate epidermal cultures, four of which were grafted onto the patient's back and right leg 29 and 35 days later. Three of these epidermal cultures engrafted successfully, in spite of infection with Pseudomonas aeruginosa, which resulted in the loss of some of the conventional, split-thickness meshed autografts that were applied concurrently. The fourth graft, which may have been oriented incorrectly onto the graft bed, was largely unsuccessful, and only small islets of epithelial cells remained after 10 days. The successful grafts produced full-thickness, epidermal coverage with a good cosmetic result and little evidence of contraction during a six-months' follow-up.

Adult↗
PubMed1987

The clinical management and laboratory assessment of anal warts.

The results of a clinical and virological survey of anal warts from 85 predominantly homosexual or bisexual men is presented, together with an improved technique for the surgical treatment of these lesions. Two types of anal warts, which were classified as either "acute" or "chronic" on the basis of their appearance and clinical behaviour, were recognized commonly. However, our laboratory investigations--which consisted of the routine histopathological examination of all specimens, together with immunohistochemical testing for the common wart antigen of specimens from 30 patients and papillomavirus typing by human papillomavirus DNA probing of 27 specimens--failed to reveal any significant differences between the two classes of anal warts. By means of a dot hybridization technique with mixed human papillomavirus DNA probes for types 6 and 11 and types 16 and 18, all wart biopsy specimens that were tested were shown to contain human papillomavirus types 6/11; two specimens also contained human papillomavirus types 16/18. Southern blot hybridization studies of eight specimens revealed that five warts contained human papillomavirus type 6 only and three warts contained human papillomavirus type 11 only. Although the surgical technique that is described was successful in terms of patient acceptance and the eventual eradication of anal warts, there was a high rate of recurrence of the lesions, which necessitated repeat operations in two-thirds of the patients. The need for counselling before surgery and for regular follow-up examinations after surgery is discussed.

Acute Disease↗
PubMed1987

Detection of specific types of human papillomavirus in cervical scrapes, anal scrapes, and anogenital biopsies by DNA hybridization.

Specific varieties of human papillomavirus (HPV) infecting the anogenital region were detected in clinical samples by use of a filter hybridization technique suitable for rapid screening of cervical and anal scrapes. In this way possibly benign types (HPV6 and HPV11) could be differentiated from types thought to be capable of malignant transformation (HPV 16 and HPV 18). Cervical or anal canal cells were applied directly to nylon filters and fixed by u.v. irradiation before hybridization with mixed viral DNA probes under both low- and high-stringency conditions. In addition, probe for the human Alu-repeated DNA sequence was used to assess the relative amount of total nucleic acids in each sample applied to the filter. HPV DNA was detected in 3 of 19 cervical scrapes from patients with no past or present history of wart virus infection or cervical dysplasia. Within a positive study group totalling 71 patients, HPV (6/11 or 16/18) was detected in cervical scrapes from 24% of 41 patients who did not have visible genital dysplasia, 30% of 27 patients with visible genital dysplasia or cervical intraepithelial neoplasia (CIN) I, and in 1 of 3 patients with past CIN II/III. In addition, HPV6/11 or 16/18 DNA was detected in anal scrapes from 3 of 6 male patients and in 85% of genital biopsies. A notably high proportion (4/6) of vaginal condylomata were positive with both the HPV6/11 and the HPV16/18 mixed viral DNA probes. Of the biopsies prepared for histopathology and positive for HPV DNA, the HPV group-specific antigen could be detected in only 60%.

Anal Canal↗
PubMed1987

Comparison of mammary serum antigen (MSA) and CA15-3 levels in the serum of patients with breast cancer.

Serum levels of mammary serum antigen (MSA) and CA15-3 were evaluated in 135 individuals in order to determine their single and combined value in the diagnosis and monitoring of breast cancer. Raised MSA levels (greater than 300 IU) were found in 68% of patients with Stage I and II breast cancer compared to only 3% having raised CA15-3 levels (greater than 40 U ml-1). Of 38 patients with Stage IV breast cancer, 95% had raised levels of MSA and CA15-3 combined with each test individually detecting 82% of those with Stage IV disease. No correlation was found between MSA and CA15-3 levels. Four patients being treated for breast cancer were followed over a 5-17 week period; MSA levels correlated with disease course in 3 and CA-15 in 2. The overall sensitivity, specificity and accuracy in detecting breast cancer were 76%, 91% and 96% for MSA; and 47%, 95% and 97% for CA15-3 respectively. When both tests were used together combined evaluation gave the highest sensitivity (84%) and specificity (100%). MSA seems to be superior to CA15-3 for early breast cancer diagnosis and a combination of the two tests gave the best results for metastatic disease.

Antigens, Neoplasm↗
PubMed1987

Heterogeneity of the human transferrin receptor and use of anti-transferrin receptor antibodies to detect tumours in vivo.

The human transferrin receptor (TFR) which is present on dividing cells, many tumours and erythroid precursors is readily identified using specific monoclonal antibodies. A new anti-human TFR monoclonal antibody, HuLy-m9, is described and its distribution on cell lines, normal and tumour tissue was examined and compared with two other anti-TFR monoclonal antibodies, namely, OKT9 and 5E9. The three antibodies were shown to recognise different epitopes on the surface of the TFR and have different reactivities with in vitro cell lines. Peptide map analyses of the TFR recognised by each monoclonal antibody from the same cell line were identical; however, differences were observed between cell lines. 131I-radiolabelled HuLy-m9 was used to successfully localise a nasopharyngeal carcinoma in vivo.

Antibodies, Monoclonal↗
PubMed1987

Cell biology of cultured anogenital warts.

A simple, reliable culture system for keratinocytes from anogenital warts is described. Using this technique we found that it was possible to produce multiple confluent keratinocyte cultures from two-thirds of the surgically-excised anogenital wart specimens received in our laboratory. Some morphological and cultural differences between these cells and normal keratinocytes derived from neonatal foreskins were observed, although there was no evidence that wart-derived keratinocytes were 'transformed'. The cultures were tested for evidence of HPV-DNA replication using 32P-labelled HPV-DNA probes, for the production of viral capsid proteins using peroxidase-antiperoxidase staining and for whole virus particles using electron microscopy. Fifty-seven per cent (8 of 14) of the wart cultures tested showed persistence of HPV-DNA (5-100 copies HPV-DNA/cell genome equivalent). However, no viral proteins or particles were detected in any culture. This system may prove to be a useful in vitro model for the study of virus-cell interaction and the role of HPV in the malignant conversion of epithelial cells.

Anus Diseases↗
PubMed1987

Mammary serum antigen (MSA) levels as a marker for breast cancer: a survey of blood donors and patients with cancer.

A murine monoclonal antibody (3E1.2) to human breast carcinoma cells was made. The antibody, which was selected for its ability to react with formalin fixed sections of the immunizing tissue, detects an antigen in the serum of breast cancer patients which we have called Mammary Serum Antigen. Immunoperoxidase staining has shown that there is an increased expression of this antigen on malignant breast epithelium compared to normal breast epithelium and other normal tissues. An assay (a serum inhibition enzyme immunoassay) using this antibody has been established to determine levels of MSA in patients' sera. Two independent studies involving greater than 2,000 blood donors and greater than 400 patients with breast cancer have shown that MSA is elevated in patients with carcinoma of the breast. MSA levels were found to be raised in approx. 2% of blood donors, approx. 55% of patients with localised breast cancer (Stage I and II) and in approx. 85% of patients with advanced breast cancer (Stage III and IV). Raised levels were also found in some patients with benign breast disease and other tumors, however these were generally much lower than those found in breast cancer patients. MSA levels may therefore be of some use for the monitoring of breast cancer patients, and as a diagnostic aid to screen populations for breast cancer.

Antigens, Neoplasm↗
PubMed1986

Visualization of metastases from colon carcinoma using an iodine 131-radiolabeled monoclonal antibody.

A murine monoclonal antibody that reacts with human colonic cancer (250-30.6) was labeled with radioactive iodine (131I) and the antibody was injected intravenously into 15 patients with known metastases originating from carcinoma of the colon (10 cases), malignant melanoma (1), breast (1), pancreas (1), hepatocellular carcinoma (1), and adenocarcinoma of unknown origin (1). Of the patients with metastatic colon carcinoma, there were 19 known deposits as judged by the techniques of clinical examination, x-rays, and scans obtained using sulpha-colloid. Of these 19 deposits, 17 (90%) were found using the 131I-labeled monoclonal antibody. In one case, the primary tumor, previously undiagnosed, was found. In only 1 of the 10 patients was tumor not found and this was due to the subsequent finding that the undifferentiated tumor did not react with antibody. Of the five patients who did not have carcinoma of the colon, three had negative scans, but two were positive. Thus, the technique of immunoscintography can readily detect both primary and metastatic tumors.

Adenocarcinoma↗
PubMed1986

Epidermal cell populations and antigen expression in cultures of human neonatal epidermis.

The persistence of Langerhans cells, melanocytes and ABH red cell antigens in human epidermal cell cultures derived from neonatal foreskin explants has been investigated. Langerhans cells were recognised via the detection of ATPase activity and by immunohistochemical staining for T6 and HLA-DR antigens. Melanocytes were detected by the dihydroxyphenylalanine (DOPA) technique; whilst the presence of red cell antigens was confirmed by immunohistochemical tests using monoclonal anti-A, anti-B, and anti-H antibodies. Langerhans cells were not detected in the cultured epidermis, and few melanocytes were found more than 0.2 mm from the periphery of the explants. However, both Langerhans cells and melanocytes were found to persist for up to 4 weeks in the explants themselves. Red cell antigens, consistent with the blood group of the donor infant, were consistently detected on the surface of the differentiating keratinocytes throughout their in vitro lifespan. The significance of these findings is discussed.

ABO Blood-Group System↗