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Biomedical subjects

L Lindholm

Publications and source records attributed to L Lindholm.

At least 91 records · Page 5Linked to original sources
PubMed1990

Hypertension and ageing.

Hypertension is a common problem in the elderly with a prevalence approaching or exceeding 50%. The risk of cardiovascular disease and death is increased in elderly hypertensives aged 60-74 years, whereas this increased risk seems to be diminished or even nonexistent in those aged 75 and above. Hypotensive drug treatment has been shown to be beneficial for the younger elderly patients, but whether or not this is also true for the older elderly hypertensives is less clear. Isolated systolic hypertension increases the cardiovascular risk, but we lack data on the efficacy of treatment in this group.

Aged↗
PubMed1989

Immunohistological detection of fucosyl-GM1 ganglioside in human lung cancer and normal tissues with monoclonal antibodies.

With the aid of a highly specific murine monoclonal antibody, F12, an immunofluorescence method was elaborated that allowed sensitive and specific detection of the ganglioside antigen fucosyl-GM1 (IV2FucII3NeuAcGgOse4Cer) in different types of human lung cancer and normal tissues. Nineteen of 21 cases of small cell lung cancer were positive with the F12 immunofluorescence method as compared to 2 of 10 squamous epithelial cell lung cancers and 1 of 5 large cell lung cancer specimens. Specimens of lung adenocarcinoma (8 cases) and bronchial carcinoid (3 cases) were all negative, as were 2 examined cases of neuroblastoma. No fucosyl-GM1 could be detected in normal lung and bronchus. However, in thymus, spleen, and lamina propria of the small intestine sparsely distributed clusters of small round cells were stained as well as intramural ganglionic cells of the small intestine and islet cells of the pancreas. All other normal tissues tested were negative. Results obtained with immunofluorescence closely agreed with immunochemical determination of fucosyl-GM1 in lipid extracts of tissues. Our findings suggest that fucosyl-GM1 is strongly associated with small cell cancer of the lung and demonstrate that this tumor-associated antigen can be detected with high sensitivity and specificity with an immunofluorescence method based on the use of the F12 monoclonal antibody.

Animals↗
PubMed1989

Influence of renal failure, rheumatoid arthritis and old age on the pharmacokinetics of diflunisal.

The single-dose plasma kinetics of diflunisal was studied in healthy young and old subjects, in patients with rheumatoid arthritis, and in patients with renal failure. The plasma and urine kinetics of the glucuronidated metabolites of diflunisal were studied in the healthy elderly subjects and in the patients with renal failure. In addition, the multiple-dose plasma kinetics of diflunisal was assessed in healthy volunteers and in patients with rheumatoid arthritis. After a single dose of diflunisal the terminal plasma half-life, mean residence time and apparent volume of distribution were higher in elderly subjects than in young adults. No difference was observed in any pharmacokinetic parameter between age-matched healthy subjects and patients with rheumatoid arthritis. The elimination half-life of unchanged diflunisal was correlated with the creatinine clearance (r = +0.89) and its apparent total body clearance exhibited linear dependence on creatinine clearance (r = +0.78). In patients with renal failure, the terminal plasma half-life and mean residence time of diflunisal were prolonged. The renal and apparent total body clearances were lower, the mean apparent volume of distribution was higher and the mean area under the concentration-time curve extrapolated to infinity (AUC) was greater in the renal failure patients than in controls. The plasma concentration of the glucuronidated metabolites rapidly rose to levels above those of unchanged drug in renal patients, whereas they were lower than those of unchanged diflunisal in controls. The AUC (0-96 h) of diflunisal glucuronides in the patients was four-times that in controls, and the terminal elimination half-life of the glucuronides was prolonged in them. The renal excretion and clearance of diflunisal glucuronides were reduced when renal function was impaired. After multiple dosing, the pre-dose steady-state plasma-concentration increased with decreasing creatinine clearance (r = -0.79). When the plasma concentration exceeded 200 mumols.l-1, the elimination half-life was doubled, due to partial saturation of diflunisal conjugation. This finding suggests that lower doses could be used in long-term treatment. Thus, old age and arthritic disease appear to have little influence on the kinetics of diflunisal in the absence of renal functional impairment. Ordinary doses can be given for short term treatment of elderly patients with or without RA. In patients with renal failure, however, reduced doses of diflunisal are recommended.

Adolescent↗
PubMed1989

Kinetics of radioiodinated monoclonal antibodies in the rat. Influence of tumour growth and reticuloendothelial system host modulation.

This experimental study in rats examines the influence of tumour growth and RES function modulation on the kinetics of iodinated MAb IgG1 C241. The study was designed to investigate unspecific accumulation in liver and blood. C241 is raised against human colon adenocarcinoma COLO 205 and reacts with SiLea tumour-associated antigen, also known as tumour-associated antigen 19-9. In 26 rats, 2 micrograms 125I MAb C241 (lodobead labelling method) was given i.v. Blood, organ and tumour content was measured at 0.5, 24, 72 and 144 h. In 61 rats, 10 micrograms 131I MAb C241 (lodogen labelling method) was given i.v. The rats were divided into a non-tumour and a tumour-bearing group and subjected to RES function modulation with Zymosan stimulation or methyl palmitate depression. A syngeneic nitrosoguanidine-induced colonic carcinoma--mean 11 g--was growing in back subcutaneous tissue and hind leg musculature. Serum content of tumour-associated antigen was not found on IRMA testing and tumour content of SiLea ganglioside antigen was found only on lipid binding phase assay. The half-time in blood of iodinated MAb C241 was three days. In-vivo release of iodine was tested by plasma separation on a gel column. More than 90% of the iodine was in the IgG fraction. The activity distribution was almost in equilibrium after 24 h. A tumour/blood activity concentration ratio of 0.5 and liver/blood ratio of 0.3 remained at 72 h and 144 h. Radionuclide accumulation was equally low in the macrophage-rich liver and the kidneys. Tumour-bearing animals had significantly lower blood content (0.37 versus 0.99% g-1) and liver content (0.09 versus 0.31% g-1) at 144 h than non-tumour-bearing rats. The whole body content at 144 h was also lower (24% versus 35% of administered activity) (p = 0.10). Modulation of RES function had no significant influence on the whole body, blood or liver content of 131I MAb C241 activity in non-tumour-bearing animals. In tumour-bearing animals, RES stimulation with Zymosan increased the whole body, liver and blood content of 131I activity. The two tested methods of iodination gave similar results.

Adenocarcinoma↗
PubMed1989

Evaluation of the therapeutic use of radioactive monoclonal antibodies C242 and C215 in transplanted murine tumours.

The therapeutic roles of monoclonal antibodies C242 and C215 labelled with 131I were investigated in transplanted mammary carcinomas. Fragments (10 mg) of mammary tumour from (A x Pc) F1 hybrid mice were implanted subcutaneously in 72 mice of the same strain. Twelve mice were injected with 131I-C242 starting from day 12 following tumour implantation, and eight out of 12 survived for 60 days. By contrast all but one of 36 control mice died within the same time period (P less than 0.0001). Twelve mice were injected with 131I-C215. Seven out of the 12 were alive at 60 days whilst all but 1 of 36 control animals had died (P less than 0.0001). In this study targeted immunotherapy using 131I-labelled antibodies C242 and C215 inhibited tumour growth and prolonged survival. Measurements of tumour area showed a 27-39 percent reduction in the mice receiving the radiolabelled conjugates C242 and C215 (P less than 0.004 and P = 0.028 respectively).

Animals↗
PubMed1988

Mouse monoclonal antibodies for experimental immunotherapy promotes killing of tumor cells.

Monoclonal antibodies (MAbs) produced against a human colon adenocarcinoma cell line, Colo-205, were tested in antibody-dependent macrophage-mediated cytotoxicity (ADMMC) assays. The antibodies C163, C215, C245 (IgG2a isotype); C151, C239, C241, C242 (IgG1); C152 (IgG2b); and C50 (IgM) were evaluated for their ability to promote killing of Colo-205 cells by thioglycollate-elicited peritoneal mouse macrophages. The concentrations of antibodies tested in ADMMC assays ranged from 1.0 ng/ml to 100 micrograms/ml, and the concentration at which 50% of tumor cells were lysed was used to characterize each antibody. Antibodies of the IgG2a isotype promoted the strongest macrophage-mediated tumor cell lysis effects in vitro. MAbs C215, C163, and C245 were also tested in nude mice which had been inoculated with Colo-205 cells. Tumor suppression was observed in mice injected with MAbs, supporting our ADMMC findings in vitro. Animals treated with MAbs had fewer and smaller tumors, and longer periods of latency between the inoculation of tumor cells and development of tumors, compared to mice sham-treated with PBS. However, in a study of established tumors, C215 antibody did not suppress tumor growth. Serum collected from MAb-treated mice promoted lysis of Colo-205 cells in ADMMC assays while serum from sham-treated mice did not.

Animals↗
PubMed1988

A clinical study of CA-50 as a tumour marker for monitoring of colorectal cancer.

Using a radioimmunoassay we have determined serum levels of the carcinoma-associated antigen CA-50 in 266 patients with colorectal cancer. Elevated CA-50 levels were found in Dukes' A (15%), Dukes' B (43%), Dukes' C (31%) and Dukes' D (65%). Patients who had developed a recurrence had 66% elevated levels. 25% of resected patients with no evidence of disease also had elevated CA-50 levels. From 139 patients operated on for a Dukes' A-C, a rise in CA-50 levels from the pre- to the 6-9 month post-operative sample was demonstrated in 12 cases in the absence of any clinical evidence for a recurrence. On follow-up, a recurrence later developed in all these cases with lead times of CA-50 titre rises ranging from 5 to 40 months. A rise in CA-50 levels after resection of a Dukes' A-C is indicative of a recurrence and may precede any clinical evidence of disease by several months or years. Data is also presented from 552 cases with colorectal cancer analysed with a immunoradiometric assay.

Antigens, Neoplasm↗
PubMed1988

A plea for more comprehensive blood pressure measurements when evaluating drug treatment of hypertension.

Blood pressure was studied at rest, continuously for 24 h and during dynamic and isometric exercise in previously untreated males with documented mild hypertension. The antihypertensive efficacy of atenolol was compared with that of enalapril in a randomized, double-blind, crossover study, in order to elucidate whether or not these more comprehensive measurements could better distinguish between the efficacy of the drugs than office recordings made at rest. Atenolol proved more effective than enalapril in reducing diastolic blood pressure at rest (P less than 0.05), and systolic blood pressure during dynamic exercise (P less than 0.001), but in the 24-h ambulatory study there were no differences in effectiveness between the drugs. Several patients did not attain our pre-set diastolic treatment goal at rest (less than or equal to 90 mmHg) on single-drug therapy, thus indicating a need for supplementary treatment. When blood pressure was analysed over 24 h, however, there were few recordings greater than 90 mmHg, and the need for supplementary treatment appeared less obvious. Therefore, more comprehensive blood pressure measurements should be considered in the evaluation of antihypertensive treatment.

Atenolol↗
PubMed1988

Blood pressure does not predict mortality in the elderly.

The purpose of our study was to estimate the extent to which casual blood pressure measurements can predict mortality in elderly people in a defined population. A random sample of subjects born between 1890 and 1914 was extracted and their medical records were studied. Their earliest blood pressure record was chosen, provided the patient was at least 60 years old at the time of measurement. The population consisted of 961 patients (49.8% women), 560 of whom died between 1968 and 1987. Their mean age was 70.1 years and the total number of person-years involved was 8625. The mortality risk was estimated as a function of sex, present age, systolic (SBP) and diastolic (DBP) blood pressures, by a version of the Cox regression model. On the basis of close confidence intervals we conclude that blood pressure in the elderly is a very weak predictor of mortality.

Aged↗
PubMed1988

Characteristics of the induction phase of antithymocyte-globulin-induced heart allograft tolerance in the rat.

Transplantation tolerance was induced in 50% of Wky rats treated with antithymocyte globulin (ATG) 2 days prior to transplantation of a PVG/c heart. The induction period immediately following ATG treatment and transplantation was characterized by instability, with 50% of the allografts being lost in rejection within 30 days after transplantation. Second syngeneic transplantation to ATG-treated recipients 5 days after the first transplantation facilitated tolerance induction and permanent acceptance of both transplants. Thirty days after ATG treatment and the primary transplantation, 50% of second syngeneic allografts were accepted. During the early period after transplantation a continuous antigen presence together with ATG was necessary. Graft removal and absence of the transplant for 3 days, close to ATG administration, resulted in rejection of a second PVG/c transplant. Furthermore, the induction phase could easily be manipulated by the addition of sensitized or tolerized spleen cells to the recipient, causing allograft rejection or tolerance, respectively. Sixty days after ATG treatment and transplantation, a longer period between graft removal and retransplantation was required to break tolerance. Injection of sensitized spleen cells at this time did not affect graft survival, indicating an increased stability of the unresponsive state 60 days after ATG treatment and transplantation.

Animals↗
PubMed1988

Localization of antibody-secreting cells against human colon adenocarcinoma cell lines using the enzyme-linked immunospot assay.

The enzyme-linked immunospot assay was used to detect antibody-secreting cells from mice immunized against three human colon adenocarcinoma cell lines (Colo-205, SW 620, and SW 1116) on dishes coated with these cell lines. Antibody-secreting cells were detected by the development of a dark granular precipitate ('spot') using immunoenzymatic techniques where secreted antibody had bound to cell surface antigen. Spots can be detected by the naked eye and can be enumerated under low-power magnification. This method is specific, easily performed, versatile, and, together with conventional enzyme-linked immunosorbent assay techniques, allows for quantification of secreted antibody.

Adenocarcinoma↗
PubMed1987

Atrial natriuretic peptide and blood pressure in a geographically defined population.

Plasma atrial natriuretic peptide (ANP) was measured in 717 subjects in a cross-sectional study of patients with hypertension (treated and untreated) and normotensive controls, representatives of a geographically defined population. ANP concentrations did not differ between the groups and there was no correlation with blood pressure. These results do not support the view that hypertensive and normotensive subjects have different ANP concentrations; they also call into question the role of ANP in the development of high blood pressure.

Adult↗
PubMed1987

Circulating immune complexes in untreated psoriasis. A comparison of Raji-cell radioimmunoassay and polymorphonuclear leukocyte phagocytosis.

Three different in vitro assays for the demonstration of circulating immune complexes were compared in 49 patients with psoriasis. Granulocytes from psoriatic subjects contained immune complex-like material in 25 patients (51%). When psoriatic serum was incubated with granulocytes from healthy blood donors, phagocytosed material was found in 18 patients (37%). The Raji-cell assay was only positive in two of 27 subjects (7%). Of the patients 71% tested positively with one of the granulocyte phagocytosis tests. Both tests were positive simultaneously in 16% and negative in 29% of the patients. The pathogenetic significance of the immune complex-like material is unclear.

Adolescent↗
PubMed1987

Protection of renal cells against free radical damage in vitro. A morphologic and functional study on human and rabbit kidney cells.

The morphologic and functional effects of free radicals on renal cells in vitro were investigated, as well as the possibility of avoiding them by pretreatment with scavenger enzymes or a xanthine oxidase inhibitor. Cultured human kidney cells, incubated together with a free radical-generating system, with and without protective agents, were examined by light and scanning electron microscopy. The vimentin filament structure of the incubated cells was visualized by immunofluorescence. The membrane function was studied in human kidney cells by using a dye exclusion test and in rabbit kidney slices by determination of the sodium-potassium pump activity. Exposure of the cells to free radicals caused rapid development of severe morphologic lesions, including extensive cytoskeletal disorganization. After pretreatment, only a few cells had similar, although less severe, lesions. The results of the dye exclusion test and indirect evaluation of the sodium-potassium pump activity did not indicate any major damage to the cell membranes after exposure to free radicals.

Animals↗
PubMed1987

Evidence of donor-specific cellular suppressor activity in donor-specific cell-mediated lympholysis unresponsiveness in renal transplant patients.

Twenty patients with well-functioning kidney grafts from one-haplotype-mismatched related donors, were studied 1-10 years after transplantation (A). Another group of six patients were studied at various times after transplantation (B). The presence of donor-specific transplantation tolerance, using mixed lymphocyte culture (MLC) and cell-mediated lympholysis (CML) tests was investigated, as well as the possible existence of cells with suppressive activity. All recipients were transfused prior to transplantation and treated with conventional immunosuppression. The patients in group A showed MLC reactivity against donor and third-party cells, indicating a allogeneic response capacity. The CML activity against the donor was low, however, and remained low also following removal of adherent cells. The CML activity toward third-party cells was within the normal range of unmatched individuals. In group B, two of six recipients and high postoperative CML activity against the donor. Both recipients showed clinical signs of rejection. In the remaining four recipients, the antidonor CML reactivity one week after transplantation was lower than the preoperative level. The decrease was even more pronounced at 12 months, although the reactivity against third-party cells was unaltered. The CML reactivity from unrelated fourth-party individuals toward donors was suppressed when cells from recipients with long-term functioning kidneys were added to the cell cultures. The results suggest the presence of a donor-specific cellular suppressor mechanism underlying the donor-specific CML unresponsiveness in recipients with long-term-functioning kidney allografts.

Adolescent↗
PubMed1987

Mechanisms maintaining transplantation tolerance in antithymocyte globulin-treated rats.

A model for induction of permanent PVG/c heart allograft survival in adult WKy rats, following antithymocyte globulin (ATG) treatment, was studied. Attempts to induce acute rejection of permanently accepted grafts, by injection of presensitized spleen cells, were successful only if the tolerant recipients had been pretreated with cyclophosphamide. Tolerance against second allografts from the primary donor strain could not be abrogated by injection of presensitized cells shortly after grafting. After removal of the permanently accepted graft, the tolerant recipients regained their capacity for acute rejection within 100 days. Tolerance was adoptively transferred with spleen cells, obtained from tolerant rats, to syngeneic sublethally irradiated recipients. The transferred unresponsiveness was donor-specific, antigen-dependent, and could again be transferred to irradiated recipients. The transferred suppression was abolished by the addition of presensitized, but not by naive, syngeneic spleen cells. The results indicate that donor-specific, antigen-dependent suppressor cells are essential for the maintenance of ATG-induced allograft acceptance. The suppression may influence the generation and activation, as well as the function, of alloreactive cells.

Animals↗