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Biomedical subjects

L Lindholm

Publications and source records attributed to L Lindholm.

At least 109 records · Page 6Linked to original sources
PubMed1987

Identification of basal cell carcinomas by means of monoclonal antibodies C50 and C241.

The monoclonal antibodies C50 and C241 with specificities for the carcinoma-associated carbohydrate structures sialylated Lea and sialosyllactotetraose, respectively, were used in the indirect immunofluorescent test for demonstration of malignant cells in patients with basal cell carcinoma (BCC). Among a total of 36 patients with BCC, 33 were positive with the MAb C50, and 30 with the MAb C241. All of five patients with premalignant conditions were positive with both antibodies, whereas none of 31 control individuals (biopsies from normal skin or from patients with non-malignant conditions) showed a positive reaction. It is suggested that the technique described may provide a convenient tool for evaluation of samples obtained by microscopically controlled surgery of BCC as well as being an adjunct to conventional light microscopy in pathologic-anatomic diagnosis of potentially malignant disease of the skin.

Antibodies, Monoclonal↗
PubMed1987

Serum levels of the carcinoma-associated antigen CA 50 in ulcerative colitis.

The aim was to study the serum level of the carcinoma-associated antigen CA 50 as a marker of dysplasia in ulcerative colitis. Seventy-four patients with a mean history of ulcerative colitis of 16 years (SD, 9 years) underwent colonoscopic examination of the entire colon. Dysplasia was diagnosed by light microscopy of multiple biopsy specimens obtained during colonoscopy. Increased serum levels of the antigen CA 50 were found in four patients, of whom two had no signs of dysplasia. Six out of eight patients with moderate dysplasia had serum levels of CA 50 not exceeding a reference level determined as the mean + 2 SD of the results in sera of 500 blood donors. Of 5 patients with ulcerative colitis for more than 30 years, 2 had increased levels of CA 50, whereas only 2 out of 69 with shorter disease duration did (p less than 0.02). Longitudinal studies are required to determine whether measurement of carcinoma-associated antigens will provide clinical information for the treatment of patients with ulcerative colitis.

Adult↗
PubMed1987

STOP-Hypertension--preliminary communication from the pilot study of the Swedish Trial in Old Patients with Hypertension.

The Swedish trial in old patients with hypertension (STOP-Hypertension) is a multicentre, randomized, double-blind study of beta-blockers/diuretics versus placebo in old hypertensives. Primary end-points are stroke and myocardial infarction (fatal and non-fatal) as well as other cardiovascular mortality. To evaluate the logistics of STOP-Hypertension, a pilot study was carried out. All patients aged 70-84 years in 31 centres were consecutively registered in a log-book. Altogether 4668 patients were screened: 41.5% had previously been treated for hypertension and 13.5% had blood pressures greater than or equal to 180/105 mmHg. Thus, 55% were 'hypertensive'. In all, 465 patients (18% of the 'hypertensive' patients) started a 3-month washout period (previously treated, n = 396) or a 4-week run-in period (previously untreated, n = 69) period. The most frequent reasons for not starting the run-in/washout were other indications for treatment with beta-blockers/diuretics (13%), unwillingness to participate (8%) or isolated systolic hypertension (4%). The pilot study was evaluated after 1 year: 89 patients (1.9%) had been randomized, 66 patients (1.4%) were still in the run-in/washout period and the majority of the remaining patients were not randomized because they had not reached the inclusion blood pressure (greater than or equal to 180 mmHg systolic and/or greater than or equal to 105 mmHg diastolic) following withdrawal of their antihypertensive medication. During the run-in/washout period there were few serious clinical events: one case of myocardial infarction, three patients had strokes (two fatal), 10 developed congestive heart failure, three tachyarrhythmia and two pneumonia (one fatal).(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic beta-Antagonists↗
PubMed1986

Binding specificity of monoclonal antibodies to ganglioside, Fuc-GM1.

The binding specificity of thirteen mouse monoclonal antibodies reacting with Fuc-GM1, Fuc alpha 1-2Gal beta 1-3GalNAc beta 1-4(NeuAc alpha 2-3)-Gal beta 1-4Glc beta 1-1Cer, a ganglioside found to be associated with small cell lung carcinoma (O. Nilsson et al. (1984) Glycoconjugate J. 1, 43-49) was studied. The results are based upon radioimmunodetection of their binding to structurally related glycolipids adsorbed to microtiter plates or chromatographed on thin-layer plates. Four of thirteen antibodies reacted only with Fuc-GM1 and both the fucose and the sialic residues were necessary for binding. Optimal binding was obtained when the sialic acid was N-acetylneuraminic acid. When this sialic acid residue was substituted with N-glycoloylneuraminic acid the binding activity was reduced and up to 10-times more Fuc-GM1 was needed for detection. The ceramide composition did not influence the binding. The other nine monoclonal antibodies cross-reacted with glycolipids containing structures closely related to Fuc-GM1 and differed from the specific ones by recognizing a smaller portion of the carbohydrate moiety in Fuc-GM1. These results indicate that anticarbohydrate monoclonal antibodies, recognizing structures involving a large proportion of the sugar in the glycolipid, possess a high specificity and might be useful for detection of tumor-associated ganglioside antigen.

Animals↗
PubMed1986

Successful treatment of autoimmunity in MRL/1 mice with LS-2616, a new immunomodulator.

Autoimmune MRL/1 mice were treated with a recently developed substance with immunomodulating properties, LS-2616. Treatment was initiated at the age of 8 weeks, before the onset of clinically apparent disease, and at 16 weeks of age, after development of established lupus disease. Beneficial therapeutic effects were obtained, even when LS-2616 was administered at the lowest dose tested (1 mg/mouse/week) to 16-week-old mice. The effects of LS-2616 on longevity, as well as on development of lymphadenopathy, splenomegaly, glomerulonephritis, and vasculitis, were pronounced and were comparable with those of cyclophosphamide. The results obtained suggest a potential role for LS-2616 in the treatment of autoimmune disease in humans.

Adjuvants, Immunologic↗
PubMed1986

Hypertension, age, and smoking related to genotoxic sensitivity in human lymphocytes: a population study.

The levels of N-acetoxy-2-acetylaminofluorene (NA-AAF)-induced unscheduled DNA synthesis (UDS) were determined in resting mononuclear leukocytes from males in a geographically defined population. The mutagen sensitivity, as determined by the NA-AAF method, was associated with the risk indicators of cerebrocardiovascular disease (CCVD) rather than with CCVD itself. Thus, high blood pressure, age, and smoking--some of the most important risk indicators of CCVD--seem to be conditions which predispose an individual's mononuclear blood cells to increased likelihood of accumulating DNA damage. Hypertensives evidenced higher values of NA-AAF-induced UDS than did nonhypertensive controls, even though the former were treated in accordance with internationally accepted norms. We have previously shown that hypertensives with normalized blood pressure did not differ from controls, when assessed by the NA-AAF method. In the present study, the hypertensives' blood pressure values were 19/12 mm Hg higher than those of the controls, indicating a need for more intensive treatment. Borderline hypertensives did not differ from their controls when assessed by the NA-AAF method, even though their blood pressure values were 19/9 mm Hg higher than those of their controls. This indicates that the group of borderline hypertensives may be heterogeneous, and that some of the patients may be suffering from a condition different from that in those with established hypertension.

2-Acetylaminofluorene↗
PubMed1986

U-shaped association between mortality and blood pressure in a thirteen-year prospective study.

The present study was performed to investigate the predictive value of casual blood pressure recordings for mortality in a geographically defined population (n = 1917), for which the primary health care services are responsible. Isotonic regression of blood pressure on age was used to define groups with low, medium and high blood pressure. In the age group 40 to 69 years mortality turned out to be a U-shaped function of blood pressure. In those aged 70 years and over blood pressure appeared to be of less importance as a risk indicator of death. The study has shown that a limited number of subjects in a defined population can be utilized in epidemiological studies of mortality as a function of blood pressure if an appropriate statistical method is used in the analyses, thereby justifying our model for studies in primary health care.

Adolescent↗
PubMed1986

Swedish trial in old patients with hypertension. A prospective multicentre study in Swedish primary health care.

The Swedish trial in old patients with hypertension was initiated by the Swedish League against Hypertension. It will be conducted as a prospective multicentre study in Swedish primary health care, and will comprise approximately 2 000 patients on active treatment and 2 000 on placebo to be studied for three years. The primary goal with this study is to investigate whether pharmacological treatment of hypertension in men and women aged 70-84 years will reduce the incidence of fatal and nonfatal cardiac and cerebrovascular disease. Before starting the main trial a pilot study comprising 400 patients will be carried out during one year to evaluate all logistical aspects of the study. This pilot study commenced in October 1985.

Adrenergic beta-Antagonists↗
PubMed1986

Detection of a ganglioside antigen associated with small cell lung carcinomas using monoclonal antibodies directed against fucosyl-GM1.

Monoclonal antibodies with an apparent specificity for fucosyl-GM1 (Fuc-GM1) were produced by the immunization of mice with Fuc-GM1 adsorbed to Salmonella minnesota bacteria and fusion of the spleen cells with the myeloma cell line Sp 2/0. The antibodies detected Fuc-GM1 with a unique ceramide composition containing 2-hydroxy fatty acids in 11 of 12 cases of small cell carcinoma of the lung. Trace amounts of Fuc-GM1 were detected in 1 of 11 squamous epithelial cell lung carcinomas. Fuc-GM1 was also detected in 1 of 7 pancreas carcinomas but was not detected in any of the other cancers analyzed. Small amounts of Fuc-GM1 without 2-hydroxy fatty acids were detected in normal adult pancreas, spleen, and brain but could not be detected in normal lung tissue. Fuc-GM1 with 2-hydroxy fatty acids is suggested to be a specific ganglioside associated with small cell lung carcinomas. The monoclonal antibodies directed against Fuc-GM1 may be useful for specific immunodiagnosis of small cell lung carcinomas and might also be useful for specific immunotherapy of these malignant tumors.

Animals↗
PubMed1985

Monoclonal antibodies raised against NeuAc alpha 2-6neolactotetraosylceramide detect carcinoma-associated gangliosides.

Monoclonal antibodies wee obtained by the immunization of mice with 6'LM1 (IV6NeuAc-nLcOse4Cer) adsorbed to Salmonella minnesota. The monoclonal antibodies showed a specificity for gangliosides with a terminal NeuAc alpha 2-6Gal substitution, which was demonstrated in solid-phase binding assay and in liposome inhibition assay. Gangliosides with a NeuAc alpha 2-6Gal substitution were minor components of different normal tissues. However, these gangliosides were enriched in carcinomas of many tissues, and were particularly enriched in most colorectal carcinomas and in lung carcinomas. 6'LM1 is a characteristic ganglioside in fetal intestinal mucosa (meconium). This ganglioside and other gangliosides with a terminal NeuAc alpha 2-6Gal substitution might represent oncofetal antigens expressed in carcinomas owing to an activation of a "fetal' sialyltransferase.

Animals↗
PubMed1985

Chemical structure of carcinoma ganglioside antigens defined by monoclonal antibody C-50 and some allied gangliosides of human pancreatic adenocarcinoma.

A hybridoma, C-50, obtained by fusion of mouse myeloma cells with spleen cells from a mouse immunized with cells from the colorectal carcinoma cell line COLO 205, produced antibodies that detected ganglioside antigen in human adenocarcinomas in many organs. The major ganglioside antigen fraction isolated from liver metastases of a pancreatic adenocarcinoma, behaving as a homogenous band on thin-layer chromatography, consisted of three different gangliosides. One of them, A (25%), had the same carbohydrate structure as the ganglioside antigen defined by monoclonal antibody 19-9, NeuAc alpha 2-3Gal beta 1-3(Fuc alpha 1-4)GlcNAc beta 1-3Gal beta 1-4Glc-Cer(Fuc-3'-isoLM1) Magnani, J.L., Nilsson, B., Brockhaus, M., Zopf, D., Steplewski, Z., Koprowski, H. and Ginsburg, V. (1982) J. Biol. Chem. 257, 14365-14369). The major ganglioside, B (60%), was the isomeric hexasaccharide ganglioside (NeuAc alpha 2-3Gal beta 1-4(Fuc alpha 1-3)GlcNAc beta 1-3-Gal beta 1-4Glc-Cer(Fuc-3'-LM1) and the third ganglioside, C, was 6'-LM1, NeuAc alpha 2-6Gal beta 1-4GlcNAc beta 1-3Gal beta 1-4Glc-Cer (15%). Ganglioside B, isolated from human kidney, did not react with the C-50 MAb. Based on this result and on studies of COLO 205 cell induced tumours where the ganglioside antigen fraction only consisted of A, it is suggested that the C-50 MAb defines an antigen determinant present in A.

Adenocarcinoma↗
PubMed1985

Sialosyllactotetraosylceramide, a novel ganglioside antigen detected in human carcinomas by a monoclonal antibody.

A novel ganglioside was detected in a small cell lung carcinoma by TLC-immunostaining of gangliosides with a monoclonal antibody, the C-50 MAb. Structural characterization showed this ganglioside to be IV3NeuAc-LcOse4Cer, a hitherto unknown ganglioside. This ganglioside has also been detected as a minor component in many different carcinomas using the C-50 MAb. The normally dominant CA-50 ganglioside antigen is IV3NeuAc, III4Fuc-LcOse4Cer. Based upon solid-phase binding to IV3NeuAc, III4-LcOse4Cer and IV3NeuAc-LcOse4Cer it is concluded that the C-50 MAb recognizes an epitope present in sialylated type I carbohydrate chains.

Aged↗
PubMed1985

Utility of a population-based case-control study model with a limited number of patients in estimating risks of hypertension.

A population-based case-control study of the risks of hypertension was carried out in a primary care district where data on all patients have been registered in out- and in-patient computer schemes and where extensive studies and treatment programs regarding blood pressure have been performed for more than a decade. The results of the study, which comprised a limited number of patients, accord with those of more extensive and prospective studies. The hypertensives had high risks of developing myocardial infarction and stroke even though they were treated according to internationally accepted norms regarding blood pressure. The estimated population-attributable risk of hypertension in men was 30% with regard to myocardial infarction and 68% with regard to stroke. Smoking and hypertension were found to be independent risk indicators of myocardial infarction in men and hypertension was a strong risk indicator of stroke. Thus, a case-control study carried out in this way in a primary care district gives valid results regarding the efficacy of an antihypertensive treatment program and may therefore serve as a model for future studies in primary health care.

Aged↗
PubMed1985

Low prevalence of abdominal aortic aneurysm in hypertensive patients. A population-based study.

The prevalence of abdominal aortic aneurysms (AAA) was estimated by ultrasonography in hypertensives in the age group 50-70 years in geographically defined population. Only one case of AAA was found among 245 patients. This rather unexpected result implies a probability of less than 5% that the true prevalence of AAA is as high as 2% in hypertensives. Our population-based study indicates a lower prevalence than earlier studies based on necropsies and is an example of research cooperation between primary health care and specialized hospital care.

Aged↗