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Biomedical subjects

L Christensen

Publications and source records attributed to L Christensen.

At least 91 records · Page 5Linked to original sources

Tumour-induced hypoglycaemia due to 'big' IGF-II.

A 57-year-old woman with a slowly growing intraabdominal leiomyosarcoma developed life-threatening hypoglycaemia. Plasma C-peptide levels were low (0.08 nmol L-1 and < 0.05 nmol L-1, reference interval 0.18-0.63 nmol L-1). Total IGF-II was normal (760 ng mL-1) whilst 'big' IGF-II was markedly elevated (440 ng mL-1). After surgical tumour reduction, 'big' IGF-II levels in plasma normalized (117 ng mL-1) and the patient experienced no new episodes of hypoglycaemia. Life-threatening hypoglycaemia due to tumour production of IGF-II can be ameliorated by reduction of the tumour burden and should be kept in mind even in incurable patients.

Female↗

The prognostic value of tetranectin immunoreactivity and plasma tetranectin in patients with ovarian cancer.

BACKGROUND: Tetranectin (TN), a tetrameric, plasminogen-binding protein, was reduced in the plasma of patients with cancer and appears extracellularly in "stimulated" connective tissues, such as the proliferative, connective tissue response to carcinomas known as desmoplasia. METHODS: Tissue samples from 37 patients with ovarian cancer were examined immunohistochemically for stromal and cellular TN. Plasma samples obtained before the primary surgery were quantitated for TN. The univariate log-rank test and the multivariate Cox proportional hazards regression model were used to analyze the prognostic function of the variables. RESULTS: A significantly higher survival rate was found for patients with a low-stromal TN score and a high-plasma TN concentration, whereas the cellular TN score did not have any significance. A significant negative correlation was found between plasma TN and stromal TN (RS = -0.36; P = 0.03). Independent significant correlations were found between stromal immunoreactivity for TN and tumor grade (R = 0.67; P = 0.03) and between plasma TN and tumor stage (R = -0.29; P = 0.01). CONCLUSIONS: This study gives great expectations to TN as a useful parameter for prognostic evaluation of patients with ovarian cancer. According to the correlations, stromal TN may partly originate from plasma and enhance proteolytic degradation in the interstitial tissue, a process necessary for the spread and growth of cancer. Because plasma TN measurements are only valid when taken preoperatively, it is of great value that stromal TN immunoreactivity of stored tumor tissue can be used as a prognostic factor for ovarian cancer.

Adult↗

PNA hybridizes to complementary oligonucleotides obeying the Watson-Crick hydrogen-bonding rules.

DNA analogues are currently being intensely investigated owing to their potential as gene-targeted drugs. Furthermore, their properties and interaction with DNA and RNA could provide a better understanding of the structural features of natural DNA that determine its unique chemical, biological and genetic properties. We recently designed a DNA analogue, PNA, in which the backbone is structurally homomorphous with the deoxyribose backbone and consists of N-(2-aminoethyl)glycine units to which the nucleobases are attached. We showed that PNA oligomers containing solely thymine and cytosine can hybridize to complementary oligonucleotides, presumably by forming Watson-Crick-Hoogsteen (PNA)2-DNA triplexes, which are much more stable than the corresponding DNA-DNA duplexes, and bind to double-stranded DNA by strand displacement. We report here that PNA containing all four natural nucleobases hybridizes to complementary oligonucleotides obeying the Watson-Crick base-pairing rules, and thus is a true DNA mimic in terms of base-pair recognition.

Base Sequence↗

[War and health in Angola. Review of a patient material].

The present study compares morbidity and lethality in two cohorts of in-patients in a provincial hospital in Angola. The first cohort was recruited during a period of peace (1978/1980), while the second was recruited during a period of increased guerilla activity in the province (1988). In wartime, the total number of patients from distant areas decreased, but, the proportion of children increased. There was a marked increase in the number of diagnoses related to poverty (tuberculosis, measles, anaemia, malnutrition), as well as on increase in mortality within these diagnostic groups. Although the area around the hospital was not directly involved in heavy war, the study clearly reflects some of the impacts of war on the health of a population.

Adolescent↗

Effects of eating behavior on mood: a review of the literature.

The literature focusing on the use of food as a regulator of a negative mood state is reviewed. This literature reveals that individuals experiencing a negative mood state arising from disorders ranging from tobacco withdrawal to premenstrual symptoms make use of carbohydrate ingestion, especially simple carbohydrates, to provide a temporary lifting of mood. However, other evidence suggests that some individuals may obtain a more permanent control of their negative mood stay by eliminating simple carbohydrates from their diet. While the literature is consistent in demonstrating that carbohydrate consumption can alter a negative mood state, the underlying mechanism mediating this relationship is unknown.

Affect↗

Sarcomatoid tumours of the breast in Denmark from 1977 to 1987. A clinicopathological and immunohistochemical study of 100 cases.

One hundred sarcomatoid breast tumours, which had been diagnosed and registered in Denmark from January 1977 to January 1987, were subclassified using a combination of conventional morphological evaluation and immunohistochemistry, and the diagnosis was in each case related to clinical follow-up of 5-14 years or until death of the patient. Conventional histological examination resulted in 36 benign, 19 borderline and 18 malignant phyllodes tumours, 1 angiosarcoma and 26 non-specified sarcomatous tumours, 6 with small carcinoma-like foci. Immunohistochemical staining revealed that 23 of the non-phylloid sarcomatous tumours showed a tumour cell reaction for epithelial markers, predominantly cytokeratin and, therefore, the tumours were interpreted as metaplastic carcinomas. Clinical follow-up showed for phyllodes tumours and for the three cytokeratin-negative sarcomatous tumours local recurrence rates of 21 and 33%, respectively, whereas metastases only occurred from the angiosarcoma and from one borderline phyllodes tumour with five recurrences (5%). In contrast, metaplastic carcinomas gave rise to distant metastases in 50% of cases but no local recurrences. Axillary lymph nodes had been examined in 28 cases, 13 from metaplastic carcinomas. Only two of these showed metastatic spread, both with a pattern similar to the primary tumour. The differences in survival between patients with metaplastic carcinoma and patients with a borderline/malignant phyllodes tumour or a cytokeratin-negative sarcomatous tumour has in this study proven to be highly significant (P < 0.0001), and we find it of importance to use immunohistochemistry in the subclassification of sarcomatous breast tumours for appropriate surgery, reliable prognostic outlook and optimal postoperative therapy.

Actins↗

Effect of meal composition on mood.

The influence of simple carbohydrate, complex carbohydrate, protein, and delayed meal conditions on plasma tryptophan ratios and mood of normal subjects was investigated. In Experiment 1, 27 women consumed 1 of 4 meal conditions, had blood samples drawn, and completed mood assessment measures before and at 5 times during the next 3 hr. Experiment 2 replicated Experiment 1 except that blood samples were not drawn and an additional simple carbohydrate condition was included. The carbohydrate meal conditions elevated blood glucose levels and plasma ratio of tryptophan to other large neutral amino acids over that of the protein condition. A decline in feelings of fatigue and distress occurred 30 min postprandial regardless of condition and persisted for the rest of the study.

Adolescent↗

A double-blind comparative study of hydroxychloroquine and dapsone, alone and in combination, in rheumatoid arthritis.

Eighty patients with active rheumatoid arthritis (RA) entered a double-blind randomized study of 24 weeks duration, to compare the efficacy and toxicity of hydroxychloroquine, dapsone, and a combination of both drugs in treatment of RA. Evaluation of changes in clinical, laboratory and radiologic variables was based on 63 patients completing the trial. There was no clear difference between the three therapy groups in most inflammatory variables after 24 weeks. However, only patients receiving the combination therapy improved significantly in all clinical and laboratory variables. Nine patients in the combination group and four in each single drug group discontinued during the trial, mainly because of toxicity. Four patients taking the combination therapy withdrew because of hemolytic anemia, and none in the dapsone group. These findings suggest that hydroxychloroquine in combination with dapsone is somewhat more effective and less tolerated than single drug treatments.

Adult↗

Type-1 plasminogen activator inhibitor in human breast carcinomas.

We have investigated the occurrence of type-1 inhibitor of plasminogen activators (PAI-1) in human breast tumors. PAI-1 levels, measured by enzyme-linked immunosorbent assay, were significantly higher in malignant breast carcinomas (n = 178) than in benign breast tumors (n = 25). The levels of PAI-1 were found to be correlated with those of urokinase-type plasminogen activator (u-PA). The presence of PAI-1 in tumor extracts was also demonstrated by immunoblotting analysis. Immunohistochemical investigations by the use of monoclonal and polyclonal antibodies showed that PAI-1 was mostly localized in the tumor islands, associated with the tumor cells; in addition, it was present in vessel walls and in normal duct epithelia, but absent from the stroma. Analysis of RNA extracted from tumors by polymerase chain reaction revealed the presence of PAI-1 mRNA. We conclude that PAI-1 is present in human breast carcinoma cells, and that it is--at least partially-- produced locally, either by the cancer cells or by other cells in the tumors. We have previously demonstrated that a high level of u-PA in human breast carcinomas is associated with poor prognosis. These results, combined with our present findings, present 2 possibilities: either the cancer cells need PAI-1 in order to utilize the u-PA-mediated pathway of plasminogen activation for invasion and metastasis; or PAI-1 represents a defense mechanism against tumor invasion.

Animals↗

[Shunt-nephritis].

Infection in ventriculo-atrial shunts implanted for relief of raised intracranial pressure may, in rare cases, result in glomerulonephritis (shunt-nephritis). Most frequently, infection with low-virulent bacteria is concerned. This results in mild or subclinical symptoms with the subsequent risk that the condition is overlooked. The glomerular damage is considered to be precipitated by deposition of immune complexes in the kidneys and subsequent activation of the complement system. The renal manifestations consist of varying degrees of proteinuria, haematuria and reduction of renal function. Treatment consists of removal of the shunt. If continued relief of pressure in the ventricular system is necessary, a ventriculo-peritoneal shunt should be implanted. Normally, the prognosis of the renal disease is good. If the diagnosis and treatment are delayed, irreversible renal damage may result. Regular control of urine (proteinuria, haematuria) and blood (Hb, serumcreatinine and serum complement) are recommended in the follow up control of patients with ventriculo-atrial shunts.

Adult↗

Rigid fixation in reconstruction of craniofacial fractures.

Ninety-four patients had either isolated fractures of the skull or midface, or combined fractures of the skull, periorbit, and/or midface. Thirty-five of these patients were treated by conventional methods, including maxillomandibular fixation (MMF) 4 to 6 weeks postoperatively, wire osteosynthesis, suspension ligatures, or a head frame. The remaining 59 patients were treated with either mini-, low-profile, micro-, or 3-D titanium plate fixation (rigid internal fixation [RIF]) and comprise the patient population for this study. Of the 59 patients, 11 were female and 48 male, ranging in age from 6 to 85 years, with a mean age of 34 years. Six patients had isolated skull fractures, 9 had combined skull and periorbital fractures, 31 had isolated midface fractures, and 13 patients had combined skull and midface fractures. The follow-up period ranged from 3 to 48 months. Patients with midface fractures were placed in MMF intraoperatively, and MMF was released at the completion of the procedure. At 2 to 4 days postoperatively, the occlusion was evaluated. Fifteen of the 38 dentate patients with either midface or combined skull and midface fractures were without MMF postoperatively. Twenty-three patients showed slight occlusal discrepancies and were treated with elastic MMF for 3 to 28 days (mean, 10 days). All reductions were judged to be stable throughout the postoperative course. Based on the results, use of RIF is recommended for primary reconstruction in craniofacial trauma patients whenever possible, thereby achieving three-dimensional stability, sufficient functional and cosmetic results, and often avoiding or reducing the need for MMF.

Adolescent↗

Myofibrosarcoma of subcutaneous soft tissue of the cheek.

A low grade soft tissue sarcoma from the naso-labial fold and designated as myofibrosarcoma (sarcoma of myofibroblasts) is described using standard light microscopy techniques, immunohistochemistry and electron microscopy. Pink fibrillated cytoplasm, regarded as one of the typical histological features of leiomyosarcoma, was not obvious but immunostaining for alpha-smooth muscle actin was positive suggesting smooth muscle differentiation. By electron microscopy, tumour cells contained abundant rough endoplasmic reticulum cisternae and a large Golgi body; there were modest but numerous bundles of fine filaments with focal densities. A conventional lamina was lacking but the cell surface was characterised by fibronexus junctions in which there was a conspicuous extracellular, fibronectin-containing fibril, apparently mediating contact between cell and matrix. The tumour cells therefore showed myofibroblastic differentiation. The cell surfaces showed strong immunoreactivity with an anti-fibronectin antibody. Myofibrosarcoma is not a widely recognised entity and this case is only the 7th example to be documented in detail by means of both immunohistochemistry and ultrastructure. The combination of electron microscopy for detecting the fibronexus junction and immunostaining for fibronectin at the cell periphery is suggested as potentially useful for distinguishing myofibrosarcoma from leiomyosarcoma.

Actins↗

The distribution of fibronectin, laminin and tetranectin in human breast cancer with special attention to the extracellular matrix.

Since Coman in 1944 observed that decreased adhesiveness is a characteristic of malignant cells and Grobstein 10 years later demonstrated that epithelial and mesenchymal cells influence each other when separated by a cell-impermeable filter, components of the extracellular matrix have been suspected of playing an active role in cancer growth. Breast cancer is frequently characterized by an increase in connective tissue fibroblastic cells and extracellular matrix, the nature and molecular composition of which is gradually being revealed. Two of the most studied and hence best known components of extracellular matrix are fibronectin and laminin. They are called adhesive or structural glycoproteins, because they are part of the stabilizing scaffold, which links connective tissue cells to each other (fibronectin) and connects connective tissues with parenchymatous cells via basement membranes (laminin). Both molecules harbour a variety of specific binding sites, which allow them to participate actively in basic dynamic processes such as cell modulation, -attachment, -spreading and -migration. Tetranectin is a recently discovered protein of human plasma and nucleated cells, which is suspected of participating in tissue degradation and proteolysis through its specific binding to plasminogen, a member of the plasminogen activation system. The immunohistochemical studies of fibronectin, laminin and tetranectin, on which this thesis is based, were undertaken in order to investigate if qualitative or quantitative changes of these proteins between benign and malignant breast tissue would reflect the net effect of the different inherent characteristics of breast cancer cells known from experimental studies (i.e. unanchored growth, proteolysis, metastatic spread and de novo production of extracellular matrix components). A significant increase in stromal fibronectin was a consistent finding in all infiltrating carcinomas, permitting the discrimination between such tumors and benign proliferative lesions as well as between carcinomas with a sarcomatoid appearance and true breast carcinomas. However, as a possible consequence of tumor heterogeneity this stromal reactivity pattern varied and tended to disappear focally along the invasive front of tumors with a high metastatic potential. A concurrent increase in the tumor cell expression of FN was found in poorly differentiated tumors, which could either be due to increased fibronectin production by the more anaplastic tumor cells or internalization of exogenous fibronectin bound to its receptor. Whereas most of the extracellular fibronectin in breast cancer is thought to be produced by the stromal fibroblasts, extracellular laminin is considered a product of the epithelial tumor cells.(ABSTRACT TRUNCATED AT 400 WORDS)

Blood Proteins↗