Biomedical subjects
Publications and source records attributed to L Christensen.
We report on the case of a patient who had a laparotomy for an 8-week-old tubal ectopic pregnancy 11 days after a normal HSG. A recent normal HSG cannot exclude an extrauterine, tubal pregnancy in fertile patients.
Saccharomyces cerevisiae was inoculated into a yeast nitrogen base with either glycerol or glucose as carbon source. Cell proliferation was followed by colony counts on agar medium. Cells in the glycerol-supplemented medium divided less than once in 10 days. When glucose, 6-deoxy-glucose or protoporphyrin IX was added, the cells had doubling times of about 24 h and increased in number to about 0.5 x 10(6) cells ml-1. Addition of either of the protein kinase C activators oleoyl-acetyl-glycerol or phorbol-12-myristate-13-acetate did not activate cell proliferation in the glycerol medium. However, when (i) glucose was combined with either protoporphyrin IX or chlorophyllin, or (ii) either protoporphyrin IX or chlorophyllin was combined with either of the protein kinase C activators, the cells had doubling times of about 12 h. Hence, (i) glucose can act as both a carbon source and a signalling molecule for proliferation, and (ii) two systems are involved in activating cell proliferation in S. cerevisiae: one operating through a protein kinase C system and another through a guanylate cyclase system.
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The synthesis and DNA binding properties of bis-PNA (peptide nucleic acid) are reported. Two PNA segments each of seven nucleobases in length were connected in a continuous synthesis via a flexible linker composed of three 8-amino-3,6-dioxaoctanoic acid units. The sequence of the first strand was TCTCTTT (C- to N-terminal), while the second strand was TTTCTCT or TTTJTJT, where J is pseudoisocytosine. These bis-PNAs form triple-stranded complexes of somewhat higher thermal stability than monomeric PNA with complementary oligonucleotides and the thermal melting transition shows very little hysteresis. When the J base is placed in the strand parallel to the DNA complement ('Hoogsteen strand'), the DNA binding was pH independent. The bis-PNAs were also superior to monomeric PNAs for targeting double-stranded DNA by strand invasion.
The proportion and absolute numbers of CD4+ and CD8+ lymphocytes in peripheral blood were determined using a new manual method, the cytosphere assay (CA). This method uses small latex beads coated with monoclonal antibodies directed against the CD4 and CD8 receptors, respectively. The CA was compared with two other methods for determination of T lymphocyte subsets, flow cytometry (FC) and the immunoalkaline phosphatase (IA) method, by testing HIV-seropositive and HIV-seronegative samples from Denmark (44) and Ivory Coast (79). For HIV-seropositive samples, both the proportion and the absolute number of CD4+ lymphocytes determined by CA showed a good correlation with results obtained by FC (correlation coefficients were 0.92 and 0.74 in Denmark and The Ivory Coast, respectively) and IA (correlation coefficients were 0.94 and 0.66 in Denmark and The Ivory Coast, respectively). However, for HIV-seronegative samples the corresponding correlation coefficients were low. CD4% determinations deviated more from FC counts at higher CD4 counts than at lower levels for both seronegative and seropositive individuals. In conclusion, the CA performed best for samples from HIV-infected individuals. Before a more general utilization of the method, it is necessary to improve its repeatability and standardize its performance at all levels of CD4+ T cells.
This study was conducted to determine whether energy level can be used to distinguish depressed from nondepressed individuals and to assess the relative importance of energy level and psychosocial variables in making this distinction. Fifty-seven participants experiencing a current episode of major depression and a matched sample of nondepressed participants completed a self-report questionnaire containing measures of energy level and psychosocial variables. Discriminant analysis revealed that energy level correctly classified 93% as depressed or nondepressed, whereas psychosocial variables correctly classified 87%. Combining the energy and psychosocial variables did not increase the accuracy of classification over that achieved by using only the energy measures. The measure of exhaustion provided the greatest relative contribution to the overall discriminant function.
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An enhanced appreciation of uptake mechanisms and intracellular trafficking of phosphorothioate modified oligodeoxynucleotides (P-ODN) might facilitate the use of these compounds for experimental and therapeutic purposes. We addressed these issues by identifying cell surface proteins with which P-ODN specifically interact, studying P-ODN internalization mechanisms, and by tracking internalized P-ODN through the cell using immunochemical and ultrastructural techniques. Chemical cross-linking studies with a biotin-labeled P-ODN (bP-ODN), revealed the existence of five major cell surface P-ODN binding protein groups ranging in size from approximately 20-143 kD. Binding to these proteins was competitively inhibited with unlabeled P-ODN, but not free biotin, suggesting specificity of the interactions. Additional experiments suggested that binding proteins likely exist as single chain structures, and that carbohydrate moieties may play a role in P-ODN binding. Uptake studies with 35S-labeled P-ODN revealed that endocytosis, mediated by a receptor-like mechanism, predominated at P-ODN concentrations < 1 microM, whereas fluid-phase endocytosis prevailed at higher concentrations. Cell fractionation and ultrastructural analysis demonstrated the presence of ODN in clathrin coated pits, and in vesicular structures consistent with endosomes and lysosomes. Labeled ODN were also found in significant amounts in the nucleus, while none was associated with ribosomes, or ribosomes associated with rough endoplasmic reticulum (ER). Since nuclear uptake was not blocked by wheat germ agglutinin or concanavalin A, a nucleoporin independent, perhaps diffusion driven, import process is suggested. These data imply that antisense DNA may exert their effect in the nucleus. They also suggest rational ways to design ODN which might increase their efficiency.
Twenty consecutive breast reconstructions were done by the expansion technique. Either textured or smooth expander prostheses were used followed by silicone implants. Histological samples were taken from the capsule when the expander was removed and the implant inserted. The results show no difference in capsular formation between the groups, although the microscopic evaluations from the group with textured prostheses showed considerable numbers of silicone droplets. The patients were generally pleased with the results even though some reconstructed breasts were slightly firm when evaluated postoperatively.
OBJECTIVE: To examine the influence of low doses of dopamine (DA) (0.4 micrograms/kg per minute), on the secretion pattern of LH. DESIGN: Prospective randomized, single blind, placebo-controlled crossover study with infusion of DA or placebo in the follicular phase in regularly menstruating women with insulin-dependent diabetic mellitus (IDDM) and controls during 9.5 hours. SETTING: Department of Endocrinology, Odense University Hospital, Odense, Denmark. PATIENTS: Eight regularly menstruating IDDM women and eight controls. MAIN OUTCOME MEASURES: Mean LH, LH pulse amplitude, and LH pulse frequency. RESULTS: During placebo infusion no significant differences in basal LH values, pulse amplitude, and pulse frequency were seen between IDDM women and controls. In diabetics, basal LH levels and pulse amplitude decreased significantly during DA infusion (3.1 +/- 1.2 mIU/mL (conversion factor to SI unit, 1.00; mean +/- SD) and 0.9 +/- 0.3 mIU/mL, respectively) compared with placebo (4.5 +/- 1.1 and 1.2 +/- 0.4 mIU/mL, respectively). In normal women no significant changes were observed (basal LH 3.0 +/- 1.8 versus 3.2 +/- 1.6 mIU/mL and pulse amplitude 1.6 +/- 0.6 versus 1.5 +/- 0.9 mIU/mL). The LH pulse frequency during DA infusion was not different from placebo in either normal (9.0 +/- 2.7 versus 10.3 +/- 4.0) or diabetic women (11.8 +/- 2.1 versus 10.9 +/- 1.8). CONCLUSION: These results suggest that diabetic women are more sensitive to a small increase in peripheral DA concentration. An abnormal permeability of the blood-brain barrier in IDDM patients could explain a greater exposure of the hypothalamic structures, regulating the pituitary gonadotropin hormone secretion.
A new plasma protein, tetranectin, was discovered in 1986. It is composed of four non-covalently linked identical peptide chains, each with a molecular weight of 20 kDa. The protein structure is known and it has been found to bind to plasminogen, Ca++ and sulphated polysaccharides. All normal epithelial and mesenchymal cells contain tetranectin in their cytoplasm, but tetranectin is not seen in normal extracellular matrix. The concentration of tetranectin in blood from healthy individuals is about 10 mg/1 with slight sex and age variations. The biological function of the protein is still unknown. The amount of tetranectin in the blood is reduced in patients with various cancer diseases. The degree of tetranectin reduction in the blood from patients with ovarian carcinoma and metastasizing breast carcinoma correlates with survival. While tetranectin is absent in normal extracellular matrix, it is found extracellulary in granulation tissues and in some carcinomas of the breast and the ovary. Lifetables of patients with ovarian carcinoma show that high concentrations of extracellular tetranectin is associated with a poor prognosis. Tetranectin may be a new prognostic marker which should be included in future clinical studies evaluating the prognosis for cancer patients.
The incidence of premature craniosynostosis is 1:2000-1:4000. Ninety percent of these are simple synostosis with premature closure of one or more of the cranial sutures causing reduced or arrested growth perpendicular to the closed suture(s). Ten percent are more complex craniofacial syndromes, where hypoplasia of the maxilla is also of importance to the development of the orbits. The reduced intracranial volume may result in an increased intracranial pressure and is a contributing factor to the rather high frequency of mental retardation seen in patients with premature craniosynostosis. Early correction is necessary in order to achieve a satisfactory cosmetic result as well as prevention of secondary damage to the brain. Craniofacial syndromes with facial hypoplasia require a staged multi-disciplinary treatment. Patients with simple craniosynostosis have to be treated within the first six months after birth.
The present study compares children with measles with children with other diagnoses who were admitted to a small local hospital in Angola in the year of 1988. No differences were observed in the distributions of sex, age or lethality. Nor were any differences found between the children who died from measles and the ones who survived. The children who died from measles did so during the first days after admission. The fact that no significant differences were found shows that measles in this population affected an average of the child population. This underlines the severity of measles as a threat to the health of children in developing countries.
We have characterized regulation of type-1 plasminogen activator inhibitor (PAI-1) gene expression by phorbol 12-myristate 13-acetate (PMA) and the cAMP-inducing agent forskolin in the human breast carcinoma cell line MCF-7. PMA caused a strong induction of PAI-1, while forskolin suppressed the PMA response. Transfection experiments with fusion genes showed that sequences mediating PMA induction as well as forskolin suppression were present between base pairs -100 and -30 of the 5'-flanking region of the PAI-1 gene. The region was found to contain two Sp1 binding sites. A proximal sequence in the region, TGAGTTCA (P box), with sequence similarity to phorbol ester response elements (TRE) as well as to cAMP response elements (CRE), bound a low-abundance, as yet unidentified nuclear protein in MCF-7 cells. This sequence had a higher affinity to purified c-jun homodimer than to c-jun/c-fos heterodimer in MCF-7 nuclear extracts; it had no affinity to the proteins binding to CRE consensus sequences in these extracts. A distal TRE-like sequence, TGAGTGG (D box), had a weak affinity to c-jun/c-fos heterodimer and c-jun homodimer; binding of proteins to this sequence was facilitated by binding of proteins to the P box. Both the P box and the D box were necessary for PMA responsiveness, suggesting a cooperativity between the two binding sites. A mutation of the P box removing the CRE similarity abolished the forskolin suppression of the PMA response. We propose that the protein kinase C and the protein kinase A signal-transduction pathways, with opposite effects on PAI-1 gene expression converge by modulating differently P-box-binding proteins.
Little attention has been paid to the composition of the extracellular matrix in synovial sarcoma, a tumour showing both epithelial and mesenchymal phenotypes. As extracellular matrix participates actively in interactions between epithelial and mesenchymal tissues, further knowledge of the pathogenesis of this tumour may be provided by the study of extracellular matrix components. Therefore, we have analysed the immunohistochemical distribution of type I, III, and IV collagen, fibronectin, laminin and tenascin in four cases of synovial sarcoma. The pattern of immunoreactivity for these molecules varied according to the tissue phenotype of the tumour. Mesenchymal tissue labelled mainly for type I and III interstitial collagen and fibronectin. The epithelial component was surrounded by a laminin and type IV collagen-positive basement membrane, but punctate pericellular reactivity for laminin and type IV collagen was also detected among some mesenchymal cells. Tenascin was strongly expressed in the mesenchymal tissue immediately around epithelial structures and weakly or not at all expressed in the monophasic tumours and in mesenchymal tissue distant from epithelial elements in the biphasic tumours. These results suggest some resemblances between synovial sarcoma and the embryonic development of epithelia from mesenchymal cells, providing further support for the concept of an epitheliogenesis from the mesenchyme in these tumours.
OBJECTIVE: This study was conducted to assess the dietary intake of individuals experiencing a current episode of major depression. METHODS: Twenty-two females and 7 males experiencing moderate to severe depression completed 3-day food records. These food records were analyzed to obtain an estimate of the nutrient intake of male and female individuals experiencing a depressive episode and this nutrient intake was compared to the Recommended Dietary Allowances (RDA). RESULTS: Females, as a group, consumed a diet that provided 100% of the RDA whereas the diet of males was deficient in energy and 4 of 16 nutrients examined. Considerable variation existed in the dietary intake of both males and females with some individuals in both groups consuming a diet containing less than the RDA in one or more nutrients due to a decrease in food intake. CONCLUSION: A substantial percentage of the depressed sample consumed less than the RDA of one or more nutrients. This seems to be due to an inadequate food intake rather than a deficient diet.
Measurements of radon at 50 sites with varying geology indicate that outdoor air in Nevada is comparable to that measured nationwide by Hopper et al. (1991). The statewide median of 15 Bq m-3 (0.4 pCi L-1) is essentially the same as the nationwide median. The range is considerable: from 2.6-52 Bq m-3 (0.07-1.40 pCi L-1). Variations in these measurements can generally be correlated with different concentrations of radon in soils and uranium and its progeny in rocks. Silica-rich igneous rocks (rhyolites and granites) appear to be the main sources of high levels of radon in outdoor air in Nevada. Concentrations of radon in outdoor air generally correlate with levels of radon in soil gas. Measurements taken from heights of 0.5, 1.0, and 2.0 m above the ground suggest that radon in outdoor air reflects the local geology throughout this range of heights. Towns for which > 20% of the homes have indoor-air radon concentrations > 48 Bq m-3 (4 pCi L-1) generally have relatively high soil-gas radon, relatively high outdoor-air radon, or both.
The expression of tetranectin in colonic neoplasia was evaluated by determining the tissue distribution by immunohistological analysis of tissue sections and the antigen levels in tissue homogenates and plasma. In normal colonic mucosa tetranectin staining was predominantly found in the goblet cells whereas in adenocarcinomas this staining was confined to the tumour stroma. Colonic adenomas, benign precursors of adenocarcinomas, showed fewer tetranectin positive goblet cells and in some cases showed tetranectin expression in the stroma. Within the tissue homogenates no differences were found in the tetranectin levels between normal mucosa, adenomas and carcinomas. Patients with colonic cancer were found to have significantly decreased plasma tetranectin levels compared to healthy controls. Thus, colonic neoplasia is associated with a change in the tissue distribution of tetranectin, without an obvious change in the tissue level, and a low plasma tetranectin level.