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Biomedical subjects

H J Hansen

Publications and source records attributed to H J Hansen.

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

Baboon anti-idiotype antibodies mimic a carcinoembryonic antigen epitope.

A baboon was immunized with NP-4, a murine monoclonal antibody (MAb) to carcinoembryonic antigen (CEA). Anti-idiotype antibodies were purified from the baboon serum by affinity chromatography on a NP-4-coupled matrix, followed by adsorption of the non-specific antibodies on an irrelevant MAb. Baboon anti-idiotype antibodies inhibited specifically the binding between NP-4 and CEA. Mice immunized with baboon anti-idiotype antibodies produced antibodies to the CEA epitope recognized by NP-4. These results indicate that baboon anti-idiotype antibodies functionally mimic a CEA epitope and that they can be suitable for idiotype therapy of human CEA-producing carcinomas.

Animals↗
PubMed1990

Murine monoclonal antibodies against carcinoembryonic antigen: immunological, pharmacokinetic, and targeting properties in humans.

We have examined three 131I-labeled murine monoclonal antibodies (MAbs) against carcinoembryonic antigen (CEA), NP-2, NP-3, and NP-4, after i.v. injection in patients with diverse cancers. Although the MAbs had a similar tumor-targeting ability, several important features were discovered that have led us to the selection of one of these MAbs for further clinical evaluation. We found that it is important to evaluate MAbs with a high immunoreactivity. For example, the MAb NP-2 was used initially in patients with an immunoreactivity between 35 and 50%. Although the tumor-imaging properties of this MAb compared favorably with the affinity-purified, goat anti-CEA antibody that we used previously, further purification of NP-2 to an immunoreactivity greater than 70% uncovered a previously unknown cross-reactivity with human granulocytes. It was also discovered that the MAbs differed in their ability to complex with CEA in the blood. Plasma samples were analyzed by gel filtration at 1 or 24 h after injection. The formation of complexes with circulating CEA was dependent on the CEA:MAb ratio in the blood. NP-3 complexed to a greater degree with CEA than NP-4, but NP-2 did not complex with CEA even at CEA:NP-2 ratios of 55 to 1. NP-3 commonly showed enhanced uptake in the colon by external scintigraphy, and examination of the radioactivity in the stool showed that most of the radioactivity was associated with whole IgG and large-sized fragments of NP-3. We also compared the rate of elimination of radioactivity from the blood for all of the MAbs and compared the clearance of NP-3 to NP-4 at three different ranges of MAb protein doses (less than 1.0 mg, 1 to 5 mg, and 5 to 20 mg). The blood clearance rate for NP-3 was fastest among the other MAbs at protein doses exceeding 1.0 mg. Patients given less than 1.0 mg of NP-4 had a significantly (P less than 0.005) shorter elimination half-life than patients given more than 1.0 mg of NP-4. By virtue of NP-4's good targeting properties in patients and its limited complexation with circulating CEA, it was selected as the MAb of choice for CEA tumor imaging.

Animals↗
PubMed1990

[Follow-up of spinal analgesia with somatosensory evoked potentials and biotesiometry].

In order to estimate the possible neurotoxicity of spinal analgesia with bupivacaine (Marcain), a total of ten patients were examined neurologically prior to spinal analgesia and seven days afterwards with somatosensory evoked potentials (SEP) and biotesiometry. The objective neurological examination results and SEP were entirely unchanged. At control examination with biotesiometry, altered vibration sense bilaterally over the medial malleoli was found in one patient but not on the pulp of the great toe bilaterally. Alterations in vibration in this patient were within the intraindividual variation as described by Fagius & Wahren. The method of examination employed here has not previously been employed systematically for follow-up investigation or elucidation of neurological deficits following spinal analgesia.

Anesthesia, Spinal↗
PubMed1990

Inhibitory effects of amitriptyline on the stimulation-induced Ca2+ increase in parotid acini.

The present study demonstrates the effects of the antidepressant, amitriptyline, and the acetylcholine antagonist, atropine, on the stimulation-induced rise in cytosolic, free Ca2+ (Cai2+). The changes in Cai2+ of collagenase-isolated rat parotid acini were measured by means of the Ca2(+)-sensitive dye, fura-2. It was found that stimulation by carbachol resulted in a maximal increase of 582 +/- 34 nM (mean +/- S.E.) in Cai2+ with a ks of 5.8 +/- 1.3 microM. Adrenaline caused a rise of 380 +/- 22 nM in Cai2+ with a ks of 0.5 +/- 0.2 microM. Amitriptyline and atropine were found to inhibit the carbachol-induced rise in Cai2+ with dissociation constants (kI) of 105 and 1.25 nM, respectively, in the absence of agonist. The adrenergic-induced rise in Cai2+ was inhibited by amitriptyline with a kI of 45 nM. Amitriptyline was found to inhibit both receptor classes by a competitive or mixed type of inhibition. Similarly, atropine exerted the same type of inhibition on the acetylcholine receptor. Amitriptyline and atropine were found to be mutually exclusive for competing for substrate binding on the receptor. These findings are consistent with a common binding site for amitriptyline and atropine on the acetylcholine receptor, possibly in close proximity with, but different from the substrate binding site. The stimulation-induced cell shrinkage evoked by the loss of electrolytes and water from the acini was measured by a 90 degree light scattering signal. It was found that this method makes possible the detection of autonomic side-effects of antidepressants on acini suspended in protein-containing media.

Amitriptyline↗
PubMed1990

Preclinical evaluation of an "instant" 99mTc-labeling kit for antibody imaging.

This communication presents information on the quality and stability of a new conjugate of 99mTc to an anticancer antibody fragment and results of animal imaging and distribution studies. Clinical studies have proved that this labeled antibody can image tumors within 2 hours of i.v. injection. It is produced using an "instant kit," merely requiring addition of [99mTc]pertechnetate to a lyophilized vial containing the fragment and a pertechnetate-reducing agent. Within 5 min of addition of pertechnetate to the vial containing the fragment, [99mTc]pertechnetate is reduced and quantitatively bound to an intrinsic high-affinity receptor present in the Fab'. The Fab'-bound 99mTc is completely stable to challenge with diethylenetriaminepentaacetic acid and human serum albumin. Minimal oxidation and release of 99mTc bound to the fragment were observed when the labeled fragment was incubated for 24 h at 37 degrees C. Animal biodistribution studies were consistent with the known metabolic elimination of a radiolabeled Fab' fragment by the kidney. Tumor localization studies in athymic nude mice bearing xenografts of human colonic carcinoma (GW-39) predicted the positive results later demonstrated in clinical studies.

Animals↗
PubMed1990

Comparison of tumor targeting in nude mice by murine monoclonal antibodies directed against different human colorectal cancer antigens.

Tumor targeting of five radioiodinated murine monoclonal antibodies (MAbs) directed against human colorectal cancer were studied in nude mice bearing the GW-39 human colonic tumor xenograft. All of the MAbs are of the IgG1 isotype. Two of the MAbs (NP-4 and MN-14) are directed against a Class III carcinoembryonic antigen-specific epitope, but they differ 10-fold in their affinity. The other three MAbs recognize mucins found in colonic cancer. Mu-9 recognizes a peptide determinant similar to that described previously for a polyclonal goat anti-colon-specific antigen p. G9 identifies an organ-specific, tumor-associated carbohydrate epitope. The tumor targeting of these MAbs was compared to that of B72.3, another anti-mucin MAb. The tumor uptake of all the MAbs were similar on days 1, 3, and 7, with an average maximum accretion of between 30 and 40%/g tumor occurring by day 3. This tumor uptake was maintained for 14 days with the anti-mucin MAbs, whereas the percentage of injected dose/g in the tumor for 2 anti-carcinoembryonic antigen MAbs decreased 2-fold by day 14. Although no statistical difference could be found between the percentage of injected dose/g in the tumor for NP-4 and MN-14 (carcinoembryonic antigen MAbs), in a paired-labeled study using 131I-MN-14 and 125I-NP-4, MN-14 uptake in the tumor was consistently 1.3 times higher than that of NP-4 on all days tested. F(ab')2 fragments showed lower tumor uptake (maximum uptake for NP-4 and Mu-9 was 11% on day 1), but the faster clearance resulted in a 4- to 40-fold increase in tumor/blood ratios on day 3 in comparison to the whole IgGs. Fab' fragments had the lowest tumor uptake of the 3 forms of immunoglobulin, with a maximum of only 5%/g 6 h after injection. However, tumor/blood ratios on day 1 for the Fab' fragments were improved 3-fold over that of F(ab')2. All of these MAbs, except Mu-9, identify epitopes that can be detected in plasma, but none of the MAbs complexed appreciably when mixed in vitro with plasma containing antigen at antigen/MAb ratios anticipated to be encountered most frequently in imaging or therapy applications in humans. However, complexation of the MAbs will occur if antigen in the plasma is markedly elevated. These studies suggest that if used clinically, tumor targeting of colorectal cancer with any of these MAb IgG may be similar if these antigens are present at relatively similar concentrations in tumor.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1990

Biological considerations for radioimmunotherapy.

We have examined three methods that may be useful for improving the therapeutic efficacy of antibody-targeted radionuclides. The principal limitation of radioimmunotherapy is myelotoxicity and thrombocytopenia. These are due mainly to the length of time the radioantibody remains in the blood. The clearance time of a radiolabeled immunoglobulin G (IgG) may be decreased by using fragments prepared from the IgG. Using murine monoclonal antibodies against human colonic cancer in an animal model with a transplantable human colonic tumor, we have shown that fractionated doses of 131I-labeled F(ab')2 fragments can provide similar tumoricidal activity as a single injection of IgG, but toxicity to the normal tissues is reduced significantly at this tumoricidal level. Thus, it is expected that improved tumoricidal activity may be achieved by further escalating the dose of F(ab')2 that is administered at each injection. An anti-antibody (second antibody) may also be used to remove an anti-tumor antibody rapidly from the blood. By allowing intact IgG to be used instead of fragments, a higher percentage of the radiolabeled anti-tumor antibodies may be concentrated in the tumor to provide higher tumor doses, yet toxicity to the normal tissues may be controlled by the removal of the radiolabeled antibody from the blood. We have shown that the injection of a second antibody 48 h after 131I-labeled anti-carcinoembryonic antigen antibody is given can reduce toxicity at least 2-fold without affecting the tumoricidal activity of the radioantibody. A third method for reducing the myelotoxicity of radioantibody treatment involves the use of cytokines to increase the production of white blood cells. For example, interleukin 1 may be given prior to, or sometime after, radioantibody treatment to increase the number of circulating white blood cells and thereby reduce myelotoxicity. Thus, modification of some of the biological factors limiting radioimmunotherapy may provide for improvements in cancer treatment with radiolabeled antibodies.

Animals↗
PubMed1990

Oral mucosal lesions related to silver amalgam restorations.

A total of 49 consecutive patients with lesions of the oral mucosa that were in contact with corroding dental amalgam restorations were subdivided into two groups. In group 1 the lesions were restricted to the contact area opposing the dental restoration, whereas the extent of the lesions in group 2 exceeded that of the contact area. Epicutaneous test for mercury allergy showed that a significantly greater proportion of the patients in group 1 had positive reactions to mercury than in group 2 (p = 0.019). The amalgam restorations were replaced by composite resin or porcelain fused to gold crowns, or contact between amalgam fillings and oral mucosa was prevented by an acrylic splint. After this treatment regression of lesions was far more pronounced in group 1 than in group 2 (p less than 0.001). On the basis of these findings, contact allergy to mercury is suggested as a possible etiologic factor of the mucosal changes in group 1, and the designation contact lesion is proposed for such lesions. The lesions of patients in group 2 seem unrelated to a contact allergy to mercury, and other causes such as lichen planus should be considered.

Acrylic Resins↗
PubMed1990

Eight to ten years follow-up after carotid endarterectomy: clinical evaluation and Doppler examination of patients operated on between 1978-1980.

Follow-up information was obtained on 185 patients who consecutively underwent carotid endarterectomy eight to ten years previously. Doppler ultrasound examination was performed in 59 patients who were still alive and living within 100 miles of the hospital. Using lifetable analysis, the annual rate of focal strokes was estimated to be 2% and 1.5% on the operated and the contralateral, non-operated carotid artery, respectively. Doppler examination revealed 48% re-stenoses, including 14% occlusion and 15% greater than 50% stenosis. However, there was no association between the occurrence of restenosis and the development of symptoms, perhaps with the exception of internal carotid artery occlusion, which is not an accepted indication for carotid endarterectomy. Together with recent data from the literature, these observations challenge the indication for reoperative carotid surgery.

Carotid Arteries↗
PubMed1990

Doppler waveform analysis in evaluation of occlusive arterial disease in the lower limb: comparison with distal blood pressure measurement and arteriography.

Three Doppler waveform parameters were related to ankle/brachial systolic pressure (A/B) index and angiography in 75 patients with lower limb arterial occlusive disease (AOD). Doppler signals were obtained from ankle arteries, and following spectral analysis pulse rise time (PRT), systolic width (SW) and pulsatility index (PI) were calculated. All three waveform parameters were significantly correlated with A/B index, and a 20% reduction could be predicted with an accuracy of 93 to 80% (corrected for chance, kappa, 81 to 52%). A significant correlation was also found between the three Doppler parameters and the angiographic assessment, i.e. the non-diseased, single- and multisegmentally diseased limbs, however, the accuracy in diagnosing angiographic stenoses was not as good as when pressure measurement was used for reference. Thirteen of the patients had high ankle pressures despite significant angiographic stenoses, and generally the Doppler examination was normal in these cases. Considering the waveform parameters individually, PRT and SW demonstrated almost identical results when compared to pressure measurement as well as angiography, whereas PI seemed clearly inferior. It is concluded that simple Doppler waveform parameters may accurately predict the haemodynamic significance of proximal AOD.

Angiography↗
PubMed1990

Structure and function of masticatory muscles in a case of muscular dystrophy.

Histologic examination of muscle biopsies and functional examination comprising electromyography and force measurements in a 19-yr-old boy with muscular dystrophy showed different wasting patterns of mandibular elevator and depressor muscles. Pronounced histopathologic changes were present in the masseter muscle, whereas pathologic findings in the anterior digastric muscle were limited to increased number of cells in slightly enlarged interfiber connective tissue. The masticatory pattern was distorted, and strength of mandibular elevator muscles was less than one third of the norm, whereas depressor strength corresponded more to reference values. This difference of muscular wasting might be caused by protective enzymes in the digastric muscle and/or functionally induced damage of the masseter. As affection from muscular dystrophy may vary greatly between the masticatory muscles, structural and functional examination should be used routinely to clarify prognosis before initiation of treatment procedures.

Adult↗
PubMed1989

Two new monoclonal antibodies, EPB-1 and EPB-2, reactive with human lymphoma.

Using the Raji cell line as the immunogen source, we established stable murine hybridomas that secrete B-lymphocyte-specific monoclonal antibodies (MAbs). Two clones, designated EPB-1 and EPB-2, were selected for further study. Both EPB-1 and EPB-2 were typed by reaction with subclass-specific rabbit anti-mouse antibodies and were found to be IgG1 and IgG2a, with kappa-light chains, respectively. In radioimmunobinding and flow cytometric assays, EPB-1 and EPB-2 did not react with T-cell lines, nor with normal diploid cells. EPB-2, in contrast to EPB-1, did not react by flow cytometry with normal peripheral or bone marrow leukocytes. In normal lymphoid tissues, both antibodies were positive with germinal center and mantle zone B-lymphocytes. Additionally, EPB-1 also labeled interdigitating histiocytes in the T-cell zones. Both MAbs discriminated very well between lymphoid and nonlymphoid tissues; neither MAb cross-reacted with tested normal and solid tumor tissue specimens, or with cell lines of non-B-cell origin. Immunohistology also revealed that both MAbs stained malignant lymphoma tissue sections and cloned B-cell lymphomas, both in tissue culture and as human xenografts in nude mice. Due to the radiosensitivity of human lymphomas and the relative specificity of these two new MAbs, they appear to be potential radioimmunotherapeutic agents for human lymphoma.

Antibodies, Monoclonal↗
PubMed1989

[Erective dysfunction. Therapeutic consequences of a basal program of investigation].

During a period of nine months, 50 men aged 21-75 years were investigated on account of erective dysfunction by means of a simple outpatient programme of investigation. Five patients could be discharged after the primary contact with history-taking and information about further investigation and treatment. Forty-five patients were submitted to the programme of investigation which consisted of measurement of penile blood pressure, Doppler investigation of the penile arteries and the papaverine test. After this, ten patients (20%) could be referred for sexological advice while five were discharged as they did not desire further treatment. Sixteen patients (32%) were taught self injection. Out of the six patients (12%) in whom arterial insufficiency was demonstrated, penile prostheses were introduced operatively in four. Venous leakage from the corpus cavernosum was demonstrated in seven patients (14%) by means of cavernosometry and cavernosography. Venous ligature was performed in five with good effect in two. Thus, specific treatment could be offered to 35 men (70%) with satisfactory therapeutic results in 22 (44%).

Adult↗
PubMed1989

[Referrals for carotid surgery during the period 1977-1986. The referral pattern for patients with carotid stenosis in the catchment region of the University Hospital in Copenhagen, assessed during a 10-year period].

Although carotid endarterectomy has been carried out for over 30 years, there are as yet no investigations which prove the value of this form of treatment with certainty. Attitudes to carotid surgery also vary greatly. The authors have assessed this variation during the period 1977-1986 on the basis of the lists of patients admitted to the Department of Vascular Surgery in the University Hospital. Patients from Funen and Jutland were excluded from the material because endarterectomy is also carried out in hospitals in these regions. A total of 720 patients from two extensive municipalities and six counties were admitted. During the period involved, increase in the number of referrals and also in the number of operations carried out occurred until 1984. After this, and in accordance with the global more restrictive attitudes, fewer patients were referred. Great regional variations were found as 8-10 as many patients per 100,000 inhabitants between 50 and 70 years were referred from the Municipality of Copenhagen as from the county which referred fewest patients. It is concluded that there are considerable differences in the treatment of patients with carotid stenosis within the catchment region of the University Hospital in Copenhagen.

Aged↗