Biomedical subjects
A Christensen
Publications and source records attributed to A Christensen.
[Cryptococcal meningitis in a patient without known predisposing disease].
Cryptococcal meningitis is a rare disease. It may occur as a superinfection in AIDS patients or other immunosuppressed patients. We describe a case of cryptococcal meningitis in a non-immunosuppressed patient. Initial symptoms were fatigue, depression and headache. A correct diagnosis was made after two weeks based on microscopic examination of cerebrospinal fluid. The patient died after six days on antimycotic therapy. Cryptococcosis is a difficult diagnosis, as our case illustrates. Psychiatric symptoms are often the first clinical manifestations. Early diagnosis is crucial for the outcome. A short overview on cryptococcosis is given.
Ligand binding properties of the very low density lipoprotein receptor. Absence of the third complement-type repeat encoded by exon 4 is associated with reduced binding of Mr 40,000 receptor-associated protein.
The very low density lipoprotein receptor (VLDLR) binds, among other ligands, the Mr 40,000 receptor-associated protein (RAP) and a variety of serine proteinase-serpin complexes, including complexes of the proteinase urokinase-type plasminogen activator (uPA) with the serpins plasminogen activator inhibitor-1 (PAI-1) and protease nexin-1 (PN-1). We have analyzed the binding of RAP, uPA.PAI-1, and uPA.PN-1 to two naturally occurring VLDLR variants, VLDLR-I, containing all eight complement-type repeats, and VLDLR-III, lacking the third complement-type repeat, encoded by exon 4. VLDLR-III displayed approximately 4-fold lower binding of RAP than VLDLR-I and approximately 10-fold lower binding of the most C-terminal one of the three domains of RAP. In contrast, the binding of uPA.PAI-1 and uPA.PN-1 to the two VLDLR variants was indistinguishable. Surprisingly, uPA.PN-1, but not uPA.PAI-1, competed RAP binding to both VLDLR variants. These observations show that the third complement-type repeat plays a crucial role in maintaining the contact sites needed for optimal recognition of RAP, but does not affect the proteinase-serpin complex contact sites, and that two ligands can show full cross-competition without sharing the same contacts with the receptor. These results elucidate the mechanisms of molecular recognition of ligands by receptors of the low density lipoprotein receptor family.
A glimpse of Zen practice within the realm of countertransference.
Explore the source record for details and available documents.
Demonstration of expression of six proteins of the mammalian cell entry (mce1) operon of Mycobacterium tuberculosis by anti-peptide antibodies, enzyme-linked immunosorbent assay and reverse transcription-polymerase chain reaction.
Polyclonal rabbit antibodies were generated to synthetic peptides corresponding to predicted B-cell epitopes of six proteins of the mce1 operon of Mycobacterium tuberculosis. Antipeptide antibodies reacted with Mce1A and Mce1E fusion proteins in sonicates of recombinant Escherichia coli as well as with distinct bands in sonicates, but not in culture fluids of M. tuberculosis and M. bovis bacillus Calmette-Guérin (BCG). Polyvalent rabbit antibodies generated by immunization with sonicates of BCG bacilli reacted with synthetic peptides from the six Mce1 proteins on the solid phase in enzyme-linked immunosorbent assay (ELISA), albeit with different frequencies. The Mce1A peptide (p124-140) reacted most frequently, with seven of the nine antibodies tested, while the Mce1F peptide (p329-343) reacted with two. Used as a control, 20 polyclonal rabbit antibodies to 12 isolated proteins of M. tuberculosis and M. bovis BCG did not react with any of the six synthetic peptides, except in one case. mRNA expression of the six mce1A-mce1F genes of M. tuberculosis was demonstrated by reverse transcription-polymerase chain reaction (RT-PCR). These data indicate that all Mce1A-Mce1F proteins of the mce1 operon are expressed by in vitro-grown M. tuberculosis and M. bovis BCG.
Interventions for couples.
A substantial body of empirical research has documented both the promise and the shortcomings of psychological interventions for preventing or ameliorating marital distress. Couple therapy reduces relationship distress and may affect individual psychopathology, such as depression. However, some couples are unresponsive and others improve but relapse later. Interventions to prevent marital distress usually produce short-term changes in behavior and relationship satisfaction, but little evidence exists demonstrating a longer-term prevention effect. Furthermore, these interventions have yet to be examined on a diverse population of couples or with a diverse set of outcome criteria (e.g. effects on children). Concern about the negative impact of marital discord and divorce will continue to provide the impetus for research on more effective means of intervening with couples. Future research could benefit from a focus on a more diverse population of couples, treatment in natural settings, the development of more powerful interventions, and the examination of those interventions over longer periods of time and with more comprehensive outcome measures.
The enhancement of traditional behavioral couples therapy: consideration of individual factors and dyadic development.
There has been little effort by behavior therapists to develop couple interventions that view marriage from a content-relevant or developmental perspective. Consequently, we have delineated ways in which a perspective of intimate relationships including individual factors and dyadic development might guide the enhancement of traditional behavioral couples therapy (TBCT) with novel and improved techniques that will ultimately allows us to reach a wider range of distressed couples than our current interventions allows. Specifically, we examined the potential benefits to intervention that could occur by considering the impact of individual factors on relationship quality, using the literature on attachment patterns as an example. Further, we have discussed the potential gains to couple interventions that could occur by considering the impact of dyadic development on relationship satisfaction. We first addressed gradual changes in marriage, using intimacy as an example. Next we examined "stage of marriage" issues, using child behavior problems as an example. Finally, we considered whether or not a problem was chronic. Throughout, we have proposed utilizing TBCT as a starting point, and considering ways to enhance TBCT specifically, as it is the marital therapy for which we have the most information and empirical support.
Acceptance versus change interventions in behavioral couple therapy: impact on couples' in-session communication.
Integrative Behavioral Couple Therapy (IBCT) attempts to improve Traditional Behavioral Couple Therapy (TBCT) by incorporating an emphasis on promoting acceptance into TBCT's emphasis on behavioral change. This study examined changes in couples' communication over the course of IBCT and TBCT. Early, middle, and late sessions were coded to measure couples' communication of acceptance. Results showed that IBCT couples expressed more nonblaming descriptions of problems and more soft emotions than TBCT couples during late stages of therapy. IBCT couples significantly increased their nonblaming description of problems and significantly decreased their expressions of hard emotions and their problematic communication over time. Results support the hypothesis that structural differences between the therapies affect initial levels of emotional expression in session. Increases in nonblaming descriptions of problems were significantly correlated with increases in marital satisfaction.
Specificity of serine proteinase/serpin complex binding to very-low-density lipoprotein receptor and alpha2-macroglobulin receptor/low-density-lipoprotein-receptor-related protein.
Very-low-density lipoprotein receptor (VLDLR) and alpha2-macroglobulin receptor/low-density-lipoprotein-receptor-related protein (alpha2MR/LRP) are multifunctional endocytosis receptors of the low-density lipoprotein receptor family. Both have been shown to mediate endocytosis and degradation of complex between plasminogen activators and type-1 plasminogen-activator inhibitor (PAI-1) by cultured cells. We have now studied the specificity of binding and endocytosis by VLDLR and alpha2MR/LRP among a variety of serine proteinase/serpin complexes, including various combinations of the serine proteinases urokinase-type and tissue-type plasminogen activators, plasmin, thrombin, human leukocyte elastase, cathepsin G, and plasma kallikrein with the serpins PAI-1, horse leukocyte elastase inhibitor, protein C inhibitor, C1-inhibitor, alpha2-antiplasmin, alpha1-proteinase inhibitor, alpha1-antichymotrypsin, protease nexin-1, heparin cofactor II, and antithrombin III. Binding was estimated with radiolabelled ligands in ligand blotting analysis and microtiter well assays. Endocytosis was estimated by measuring receptor-associated protein (RAP)-sensitive degradation of radiolabelled complexes by Chinese hamster ovary cells transfected with VLDLR cDNA and by COS-1 cells, which have a high endogenous expression of alpha2MR/LRP. We found that the receptors bind with high affinity to some, but not all, combinations of plasminogen activators and thrombin with PAI-1, protease nexin-1, protein C inhibitor, and antithrombin III, while complexes of many serine proteinases with their primary inhibitor, i.e. plasmin/alpha2-antiplasmin complex, do not bind, or bind with a very low affinity. Both the serine proteinase and the serpin moieties contribute to the binding specificity. The binding specificities of VLDLR and alpha2MR/LRP are overlapping, but not identical. The results suggest that VLDLR and alpha2MR/LRP have different biological functions by having different binding specificities as well as by being expressed by different cell types.
Breast carcinoma epithelial cells express a very low-density lipoprotein receptor variant lacking the O-linked glycosylation domain encoded by exon 16, but with full binding activity for serine proteinase/serpin complexes and Mr-40,000 receptor-associated protein.
Very-low density lipoprotein receptor (VLDLR) belongs to the low-density lipoprotein receptor family of endocytosis receptors. It binds a variety of different ligands, including apolipoprotein E, Mr-40,000 receptor-associated-protein (RAP), and some serine proteinase/serpin complexes. We previously demonstrated the occurrence of two forms of VLDLR in SDS/PAGE, migrating with Mr 105,000 and Mr 130,000, respectively [Heegaard, C. W., Simonsen, A. C. W., Oka, K., Kjøller, L., Christensen, A., Madsen, B., Ellgaard, L., Chan, L. & Andreasen, P. A. (1995) J. Biol. Chem. 270, 20,855-20,869]. We now demonstrate that these two forms correspond to forms with the absence (type-II) and presence (type-I) of the O-linked glycosylation domain encoded by exon 16, respectively. We show that the two forms have the same binding affinity to RAP and serine proteinase/serpin complexes. Using reverse transcription and PCR, we demonstrate that the splice variation giving rise to the two forms is highly cell specific. In particular, we demonstrate that human breast carcinomas express predominantly or exclusively the variant lacking exon 16. By immunohistochemistry, we demonstrate that VLDLR is mainly expressed by the epithelial cancer cells in these carcinomas. The VLDLR variant expressed by epithelial cancer cells could function in the clearance of cell-surface-associated serine proteinase/serpin complexes in breast carcinomas.
A randomized, double-blind, multicentre study comparing the clinical effects of two sequential estradiol-progestin combinations containing either desogestrel or norethisterone acetate in climacteric women with estrogen deficiency symptoms.
OBJECTIVES: The aim of this study was to compare a new estradiol-desogestrel (E2-DG) regimen with an E2-norethisterone acetate (NETA) combination (Trisekvens) regarding the treatment of menopausal complaints, bleeding pattern, histology of the endometrium and the occurrence of adverse experiences. METHODS: A total of 310 peri-/postmenopausal women with climacteric symptoms were randomly allocated to oral sequential treatment with either the E2-DG combination (1.5 mg E2 for 24 days with 0.15 mg DG for the last 12 days followed by 1 placebo tablet for 4 days) or with the E2-NETA combination (Trisekvens, 2 mg E2 for 22 days with 1 mg NETA for the last 10 days followed by 1 mg E2 for 6 days). Treatments were administered double-blind for 12 cycles of 28 days. RESULTS: One hundred and four women, 48 in the E2-DG group and 56 in the E2-NETA group, discontinued the study due to bleeding irregularities and various adverse effects. Both treatments reduced menopausal symptoms and complaints effectively and almost equally. The alleviation of perspirations and the improvement of general fitness were more apparent (P = 0.009) during cycle 1 with the E2-NETA treatment but were greater (P < 0.02) during the last 9/10-12 cycles of E2-DG treatment compared to E2-NETA. Regular withdrawal bleeding appeared in 93% and 90% of the women during treatment with E2-DG and E2-NETA, respectively. Intermenstrual bleeding occurred in 8% of women receiving E2-DG and in 13% of women treated with E2-NETA. The corresponding figures for intermenstrual bleeding-spotting were 21% and 22%. Secretory endometrium was detected in 65% and 54% of the samples taken at the end of treatment with E2-DG and E2-NETA, respectively. No hyperplasia or atypia was found. No serious adverse events related to treatment occurred. CONCLUSIONS: Both regimens alleviated effectively menopausal complaints and did not induce hyperplasia of endometrium. The minor differences recorded between the two regimens were probably due to the differences in their composition concerning the amount of estradiol and its distribution along the cycle, the amount and type of progestin and the length of estradiol/progestin combination phase.
Studying the effectiveness of psychotherapy. How well can clinical trials do the job?
Although there has been much discussion of the recent Consumer Reports (CR) study (1995) on the effectiveness of psychotherapy, there is little new information reported either in the CR article or in M. E. P. Seligman's (1995) discussion of the findings. The findings that are new are hard to interpret because of serious methodological problems. In fact, the CR study is similar in many ways to H. J. Eysenck's (1952) controversial report on the effectiveness of psychotherapy, a study that has been rejected by the field despite the fact that it avoided some of the methodological shortcomings of the CR study. It would be a mistake to put forth a design rejected in the 1950s as an exemplar of good effectiveness research, especially when better alternatives exist. Clinical trials, despite many limitations, can answer all of the questions regarding the effectiveness of psychotherapy posed by M. E. P. Seligman, without the interpretive ambiguities and other methodological problems inherent in surveys such as the one published in CR.
Human papillomavirus infection in cervical biopsies from Norwegian gynecological in-patients.
Polymerase chain reaction (PCR) and Southern blotting were used to assess the prevalence of HPV in cervical biopsies of 100 women who were treated at the gynecology department of Telemark Central Hospital for non-cancerous conditions. Nine (9%) of the biopsies were HPV positive. Four (4%) were of HPV type 18, one (1%) was HPV11 positive, and four contained different unrecognized HPV types (HPVX). HPV16 was not detected.
Very low density lipoprotein receptor binds and mediates endocytosis of urokinase-type plasminogen activator-type-1 plasminogen activator inhibitor complex.
Very low density lipoprotein receptor (VLDL-R) was found to be expressed in bovine mammary gland and the human breast carcinoma cell line MCF-7 as an M(r) 105,000 variant, and in Chinese hamster ovary (CHO) cells transfected with human VLDL-R cDNA as an M(r) 130,000 variant. The receptor was purified by ligand affinity chromatography with immobilized M(r) 40,000 receptor-associated protein (RAP). The purified receptor was found to bind urokinase-type plasminogen activator-type-1 plasminogen activator inhibitor complex (u-PA.PAI-1), while there was no or very weak binding of active site blocked u-PA (DFP-u-PA), PAI-1 or u-PA-type-2 plasminogen activator inhibitor complex. The binding of u-PA.PAI-1 was blocked by RAP. The transfected CHO cells had an efficient, RAP-sensitive endocytosis of u-PA.PAI-1, severalfold higher than non-transfected parental CHO cells. u-PA.PAI-1 endocytosis was partially inhibited by DFP-u-PA, which blocks binding of the complex to the u-PA receptor. RAP and DFP-u-PA sensitive u-PA.PAI-1 endocytosis was also observed in MCF-7 cells, which were without detectable levels of other RAP-binding endocytosis receptors. These results show that VLDL-R represents a novel endocytosis mechanism for u-PA receptor-bound u-PA.PAI-1.
The longitudinal impact of demand and withdrawal during marital conflict.
Forty-eight couples completed a measure of relationship satisfaction and participated in 2 video-taped problem-solving interactions, 1 focused on an issue identified by the woman and 1 focused on an issue identified by the man. Thirty-six men and 36 women completed the satisfaction measure again 2.5 years later. Demandingness, and to a lesser extent withdrawal, during the interactions showed many significant associations with both Time 1 and Time 2 satisfaction. The relationship of demandingness and withdrawal to change in satisfaction was also examined using both change scores and partial correlations. Withdrawal by men and woman demand-man withdraw during discussions of issues identified by the women reliably predicted change (decline) in wives' relationship satisfaction.
Very low density lipoprotein receptor from mammary gland and mammary epithelial cell lines binds and mediates endocytosis of M(r) 40,000 receptor associated protein.
We here report that the M(r) 40,000 receptor associated protein (RAP), previously found to bind to alpha 2-macroglobulin receptor/low density lipoprotein receptor related protein (alpha 2MR/LRP) and glycoprotein 330 (gp330), binds to an M(r) 105,000 membrane protein from bovine mammary gland, human mamma tumors and mammary epithelial cell lines. We have purified this protein from bovine and human sources. N-terminal amino acid sequencing and immunoblotting analyses showed that the protein was identical or closely related to very low density lipoprotein receptor (VLDL-R). Experiments with the human mamma carcinoma cell line MCF-7 showed that this receptor was able to mediate an efficient endocytosis of RAP. These novel findings strongly suggest that RAP functions as a modulator of ligand binding to VLDL-R, similarly to alpha 2MR/LRP and gp330.
[Should the great saphenous vein be stripped in routine surgery for uncomplicated varicose veins?].
Stripping of the great saphenous vein is widely used in the surgical treatment for varicose veins. With the increasing demand of vein material in coronary- and femoro-distal bypass surgery, this routine creates a conflict. A review of the literature reveals the possibility of vein-saving procedures that do not increase the recurrence rates. By utilizing modern diagnostic methods, it is possible to make an exact preoperative diagnosis as to the extent of the varicose disease and thus make an individualized operation, that is just as radical as necessary, but at the same time as vein-preserving as possible.