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Biomedical subjects

J Andersen

Publications and source records attributed to J Andersen.

At least 73 records · Page 4Linked to original sources

Immunocytochemical determination of the estrogen-regulated protein Mr 24,000 in primary breast cancer and response to endocrine therapy.

Monoclonal antibodies against an estrogen-regulated Mr 24,000 cytosol protein (p24) were used for immunocytochemical localization of p24 in formalin-fixed paraffin-embedded specimens from the primary tumor in 103 patients who received endocrine therapy for advanced breast cancer. Sixty-one per cent of the tumors showed p24-positive staining, and this correlated well with the presence of estrogen receptor (ER) (P = 0.00017, chi-square test). Response to endocrine therapy was obtained in 43% of the patients. A statistically significant association between p24 status and response could not be established, while response and ER status were highly correlated (P = 0.0000029, chi-square = 21.6). Discrimination between ER-positive responders and ER-positive non-responders was not possible using p24 staining.

Breast Neoplasms

Specificity of mismatch repair following transformation of Saccharomyces cerevisiae with heteroduplex plasmid DNA.

A method is described for genetic detection of mismatch repair products following transformation of Saccharomyces cerevisiae. The method is based on the detection of beta-galactosidase activity in clonal derivatives of cells transformed with heteroduplex plasmid DNA. Heteroduplex plasmid substrates were constructed by insertion of an oligonucleotide heteroduplex into the coding sequence of the Escherichia coli lacZ gene. The plasmid and oligonucleotides were designed so that one strand of the construct would code for a functional beta-galactosidase and the other strand would contain an in-frame nonsense codon. The frequencies of transformed clones containing only Lac+ cells, only Lac- cells, or a mixture of the two Lac phenotypes provided information on the efficiency of the repair reaction. With this method, plasmids carrying single-base substitution mismatches, a single-base frameshift mismatch (T/delta), or a 3-base-pair substitution mismatch (TGA/GAA) were tested. A/C, G/T, G/A, G/G, and T/delta mismatches were repaired with significantly greater efficiencies than C/C, A/A, T/T, and TGA/GAA. T/C was repaired with an intermediate efficiency. The frequencies of products obtained with G/G, G/A, and T/delta mismatches suggested modest inequality of repair in the two possible directions. Strains carrying the repair-deficient pms1-1 mutation were also tested. The efficiencies of repair of A/C, G/T, G/G, and A/A mismatches were reduced in pms1-1 cells compared with wild-type cells. In addition, a change in repair inequality was detected when transformation of the two strains with an A/C mismatch was compared.

DNA Repair

An open, noncomparative study of amoxapine in borderline disorders.

Five patients with borderline personality disorder (BPD) and 5 patients with schizotypal personality disorder (SPD) completed at least 3 weeks of treatment with amoxapine. The patients fulfilled DSM-III criteria for borderline disorders and scored 7 points or more in Gunderson's Diagnostic Interview for Borderlines (DIB). The final median medication in patients with BPD was 200 mg amoxapine/day and 42 mg oxazepam/day. Duration of treatment averaged 28 days. In patients with SPD the corresponding figures were 250 mg amoxapine/day, 36 mg oxazepam/day and 39 days. The study suggests that amoxapine improves schizophrenic-like and depressive symptoms in patients with schizotypal personality disorders (SPD). No effect could be shown in patients with borderline personality disorders (BPD).

Adult

The GBS scale in multi-infarct dementia and senile dementia of Alzheimer type.

The GBS profile was assessed for 39 patients with multi-infarct dementia (MID) and 34 patients with senile dementia of Alzheimer type (SDAT). The MID patients fulfilled the DSM-III criteria for multi-infarct dementia and had a score of 7 points or more on the Hachinski Ischemic Scale (HIS) and a score of 4 points or less on the Gustafson/Nilsson Alzheimer Scale (GNAS). The SDAT patients fulfilled DSM-III criteria for primary degenerative dementia and had a score of 5 points or more on the GNAS and a score of 6 points or less on the HIS. The total GBS score, the GBS subscale and relative subscale scores for intellectual functioning were significantly higher in patients with SDAT as compared with patients with MID. However, these subscale scores were considerably dispersed and nearly totally overlapping between patients with MID and SDAT, which implicates that the discriminative value is minimal. The validity between the GBS versus HIS and between the GBS versus GNAS was divergent, suggesting that the GBS scale has its own unique validity. In conclusion, the study does not support the hypothesis that the GBS profile may be of diagnostic value in clinical differentiation between multi-infarct dementia (MID) and senile dementia of Alzheimer type (SDAT).

Aged

The Brief Psychiatric Rating Scale. Dimension of schizophrenia--reliability and construct validity.

This study has focussed on a 10-item Brief Psychiatric Rating Scale (BPRS) subscale for the quantification of schizophrenic states. Seven psychiatrists interviewed jointly patients who all fulfilled the DSM-III criteria of schizophrenia, and in a subsequent pencil-and-paper procedure a judgment analysis was performed. The reliability analysis showed that less experienced BPRS raters made less consistent judgments implying the cautionary statement that the proper use of a scale for schizophrenia requires specialized training with the scale. The validity analysis showed that the BPRS items had an additive relationship implying that the sum of these items is a sufficient statistic for the measurement of severity of schizophrenic states. Finally, the results seem to indicate, that the underlying dimension defined by the 10-items BPRS subscale includes hierarchically the negative and positive symptoms of schizophrenia.

Adult

Body size and menopausal status in relation to the pattern of spread in recurrent breast cancer.

The prognosis and pattern of spread were related to body size and menopausal status in 863 patients with recurrent breast cancer. These patients were all enrolled in the adjuvant protocols of the Danish Breast Cancer Cooperative Group. The pattern of spread was illustrated by the number of metastases, the anatomical location of recurrence, and the rate of progression. Body size was estimated as height, weight, Quetelet index (QI), and body surface area (BSA). The body size was unassociated with both recurrence-free interval (RFI) and survival after recurrence (SAR). The groups of patients with different body size had both the same number and the same location of metastases. The tumour growth rates were estimated as clinical rates of progression (i.e. the time elapsed from a single distant metastasis until dissemination). The progression rate was unaffected by body size. Postmenopausal patients had a significantly shorter RFI and SAR compared to premenopausal patients. The number of metastatic sites, the anatomical location of metastases, and the rate of progression were similar in pre- and postmenopausal patients. The study could not confirm most findings from the literature which report a poor prognosis for patients with large body size. Moreover, the results do not suggest interactions between body size, menopausal status, and the clinical course of recurrent breast cancer.

Anthropometry

Chromosome analysis of in situ breast cancer.

Eleven ductal carcinoma in situ (DCIS), 5 DCIS with microinvasion and 4 benign lesions have been investigated cytogenetically. Twelve of the 20 breast tumors (60%) had sufficient mitotic activity for chromosome analysis. All ductal carcinoma in situ had abnormal karyotypes, and clonal marker chromosomes could be identified in all tumors analyzed. None were cytogenetically normal. All but one of the 12 DCIS showed genetic heterogeneity. Tumor progression seems to be associated with loss of chromosomes.

Breast Neoplasms

Immunoreactive opioid peptides in human breast cancer.

Opioid peptides have a variety of actions on inter alia pituitary hormone secretion and the immune system. Release of endogenous opioids has been found to stimulate growth of experimental breast cancers and opiate receptor blockers have reduced the growth of chemically induced rat breast tumors. Opioid peptides may therefore play a role in human breast cancer. Invasive ductal carcinomas from 61 premenopausal women were immunocytochemically analyzed for the presence of opioid peptide immunoreactivity. Positive staining was unambiguously identified in 34 of the tumors (56%). In addition, a medullary carcinoma was positive. In a smaller series of tumors, opioid peptide immunoreactive cells were detected in both primary tumors and metastases. Positive tumor cells were usually few and scattered. Therefore, underestimates of their true frequency of occurrence are likely to have occurred, making accurate correlations with clinical behavior and estrogen receptor status difficult. No correlations with estrogen receptors were established for the unambiguously opioid peptide-positive tumors. Many of the positive tumors also stained with antibodies to gamma-endorphin and alpha-melanocyte-stimulating hormone, suggesting the presence of proopiomelanocortin-derived peptides in them. However, peptides derived from other opioid precursors also may be present in breast cancer.

Breast Neoplasms

In vivo analysis of castanospermine, a candidate antiretroviral agent.

Castanospermine (1,6,7,8-tetrahydroxyoctahydroindolizine), an inhibitor of glycoprotein processing, has been shown to inhibit the human immunodeficiency virus type 1 (HIV-1) with acceptable toxicity in cultured cells. In contrast to reverse transcriptase inhibitors, castanospermine targets host enzymes. We have analyzed castanospermine in murine systems, using cultured cells as well as live animals. Plaque formation by Rauscher murine leukemia virus (RLV) was inhibited with a median inhibitory concentration (IC50) of 2 micrograms/ml. RLV-exposed BALB/c mice treated with a 20 day course of castanospermine starting 4 h postinoculation showed a dose-dependent inhibition of splenomegaly. Oral castanospermine therapy given to chronically RLV-infected mice prolonged median survival from 36 to 94 days when compared to untreated controls (p = 0.007). Castanospermine was better tolerated orally than intraperitoneally at the same dose. Toxic effects included weight loss, lethargy, and dose-dependent thrombocytopenia. At the highest intraperitoneal dose, lymphoid depletion occurred in thymus, spleen, and lymph nodes. We conclude that castanospermine is an active antiviral agent in animals and that prolonged oral administration is tolerable; however, when compared to 3'-azido-3'-deoxythymidine in the same murine system, castanospermine was less active and more toxic.

Alkaloids

Elephantiasis-like cutaneous metastases from signet-ring cell carcinoma of the stomach.

We report the clinical features and course of a 66-year-old patient with gastric carcinoma, in whom multiple cutaneous metastases occurred one year after he underwent subtotal gastrectomy. Although internal malignancies rarely metastasize to the skin, when they do this may have profound diagnostic, therapeutic, and prognostic significance. Cutaneous metastases are usually synonymous with a rapidly progressive disease and a poor prognosis. This case, in which cutaneous metastases were found in the lower limbs, is notable since usually less than 4 percent of cutaneous metastatic lesions are found in this region. Moreover, the case seems unique because of the predominating dermiotrophic metastases, with only minor internal involvement.

Adenocarcinoma, Mucinous

Use of sodium-chloride separated human skin in detection of circulating anti-basement membrane zone antibodies.

The sensitivity of the indirect immunofluorescence (IIF) technique for detection of circulating basement membrane zone (BMZ) antibodies was evaluated, employing NaCl-separated human skin and intact skin as substrate. Consecutive serum samples from 12 patients with clinically, histologically and immunohistologically verified bullous pemphigoid (BP) were investigated in parallel on both substrates, in dilutions ranging from 1:10 to 1:1,280. All BP sera showed linear deposits of IgG at the BMZ on intact skin, with titres ranging from 10 to 160. On NaCl-separated skin, all BP sera produced a linear epidermal fluorescent band for IgG, with titres ranging from 80 to 1,280. None of the sera showed deposits of IgM anti-BMZ antibodies. Sera from 5 healthy donors (dilutions 1:10) produced no fluorescence, either on intact or on NaCl-separated skin. The serum-titres of circulating anti-BMZ IgG antibodies in 2 patients with corticosteroid-resistant BP were significantly reduced (from 160 to less than 10) during treatment with plasmapheresis, when using NaCl-separated skin as substrate for IIF, whereas the serum-titres showed insignificant reduction (from 20 to less than 10), when using intact skin as substrate. We conclude that the IIF method is more sensitive for detection of circulating anti-BMZ antibodies, when NaCl-separated skin as compared with intact human skin is employed as substrate.

Antibodies

Endoscopic suspension of the bladder neck by the Stamey method for urinary incontinence.

Eighteen women with stress incontinence underwent endoscopic suspension of the bladder neck by the method of Stamey. The procedure was carried out in a department of general surgery. Pre- and postoperatively the patients were evaluated by pelvic examination with stress test, colpo-cysto-urethrography, urinary flow rate measurement, cystometry, and culture of the urine. Fifteen became fully continent at once, another two after having been treated further by posterior colpoperineorraphy, while one remained incontinent. The median postoperative follow-up was 27 months. Complications were rare and mild. It is concluded that the method is applicable in departments of general surgery and that the result can be improved in selected patients by posterior colpoperineorraphy.

Adult

Stromal fibronectin staining pattern and metastasizing ability of human breast carcinoma.

The peripheral stromal fibronectin (FN) staining patterns of invasive breast carcinomas (IBC) from 77 women were compared to the aggressivity of the tumors, which in each case had been determined through a complete clinical follow-up and autopsy investigation. Polyclonal, monospecific rabbit antibody to human FN was applied on formalin-fixed, paraffin-embedded tissue sections using the peroxidase-antiperoxidase staining technique. An FN-positive staining reaction was defined as a constant, diffuse, or pericellular demarcation of FN-positive fibers surrounding tumor cells at the invasive border. In lack of such a staining pattern, FN-negative staining was recorded. The FN-positive staining reaction was significantly associated with a low metastatic potential and appeared in a multivarians analysis to be an excellent prognostic factor, which surpassed other known parameters, such as clinical stage, histological type or grade, and lymph node status. 27 out of 31 women, who died without evidence of metastatic spread, had FN-positive IBC (87%) in contrast to women with metastatic disease, where only 15 out of 46 had FN-positive tumors (33%). An extensive histopathological examination of the contralateral breast revealed in this latter group a high rate of second primaries (22/46), which might have been responsible for the metastatic spread. If these women with bilateral IBC were excluded, only three metastasizing tumors with a FN-positive staining pattern remained, suggesting that the prognostic value of the FN-staining pattern along the invasive border of IBC might be even higher than anticipated from this study.

Analysis of Variance