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Biomedical subjects

L Christensen

Publications and source records attributed to L Christensen.

At least 19 recordsLinked to original sources

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

A tetranectin-related protein is produced and deposited in extracellular matrix by human embryonal fibroblasts.

Tetranectin is a tetrameric human plasma protein that binds to plasminogen kringle 4. Its amino acid sequence is homologous with the C-terminal parts of asialoglycoprotein receptors and proteoglycan core proteins. In the present study, we have demonstrated that the human embryonal fibroblast cell line WI-38 produce a tetranectin-related molecule, which might, by several criteria, be similar to tetranectin from plasma. These criteria include immunoblotting analysis of conditioned cell medium revealing a protein band with Mr 17,000, indistinguishable from the Mr of plasma tetranectin. A preparation obtained by purification of conditioned medium by affinity chromatography on an anti-(plasma tetranectin) IgG column also contained the Mr 17,000 protein. This protein (partly purified from the conditioned medium) was shown by crossed immunoelectrophoresis to bind to heparin, CaCl2 and plasminogen kringle 4, as previously described for tetranectin in plasma. Importantly, this tetranectin-related protein is not only present in conditioned culture medium, but the Mr 17,000 protein reacting with anti-(plasma tetranectin) IgG was also present in the extracellular material, remaining after removal of WI-38 cells from the culture dishes, as demonstrated by immunoblotting analysis and immunocytochemical staining. We conclude that WI-38 cells produce a tetranectin-related protein and secrete it into the extracellular matrix.

Blood Proteins

Differences in tetranectin immunoreactivity between benign and malignant breast tissue.

Tetranectin (TN) is a human, plasminogen kringle 4 binding plasma protein with ubiquitous cellular distribution and lectin-like characteristics. By means of the peroxidase-antiperoxidase staining technique a polyclonal and a monoclonal antibody were used to demonstrate TN within the intracellular as well as the extracellular compartment of invasive breast carcinoma. Whereas cell associated TN was universal showing only quantitative differences depending of the growth pattern of the tumor, 78 of 133 tumors displayed TN extracellularly as well. The occurrence of this stromal TN immunoreactivity was closely associated with desmoplasia, recognized morphologically by an increase in fibroblastic cells and immunohistochemically by an intense staining for the connective tissue glycoprotein fibronectin (FN). Benign breast tissue displayed a universal, intense cytoplasmic but no extracellular reaction for TN, with the exception of rare foci of granulation tissue and around dilated cysts. Functional studies have shown that human embryonal lung fibroblasts increase their release of TN to the growth medium upon stimulation. The presence of TN extracellularly within fibroblast-rich foci of desmoplasia (and granulation tissue) suggests that a similar increased release of the protein takes place in vivo during active states. Desmoplasia has been found to have a protective effect on tumor cell propagation and metastasis in a murine model. The molecular interactions, which are responsible for this effect, are undoubtedly complex. However, TN may, by its specific binding to kringle 4 of plasminogen and its high affinity for sulphated polysaccharides, add to the understanding of how plasminogen activation is modulated at the local extracellular level.

Blood Proteins

Issues in the design of studies investigating the behavioral concomitants of foods.

This article discusses a number of issues that must be considered when investigating the behavioral effect of foods. These issues include the idiosyncratic response to a specific food, the necessity of identifying the individual sensitive to the food being studied, the necessity of including a washout phase, consideration of withdrawal effects, assessment of change, dietary challenges, and the time parameter necessary for the effect to be demonstrated. These issues must be considered during the design phase to maximize the probability of detecting the true behavioral effect of a specific food or combination of foods.

Depressive Disorder

Efficacy of caffeine versus expectancy in altering caffeine-related symptoms.

The study investigated the independent and interactive effects of caffeine and expectancy on caffeine-related symptoms. High- and low-caffeine consumers were randomly assigned to either an expectancy or nonexpectancy instructional set and one of four caffeine doses. Subjects were administered the State-Trait Anxiety Inventory, (Spielberger & Gorsuch, 1970) and a Symptom Questionnaire (Christensen, White, Krietsch, & Steele, 1990) prior to and 45 min following consumption of one of the four caffeine doses. An analysis of covariance identified a significant main effect for the State-Trait Anxiety Inventory scores and significant main and interaction effects for four Symptom Questionnaire items. However, when the alpha levels were corrected for the increased probability of Type I error, using the Bonferroni procedure, these effects failed to achieve significance. These results suggest that previous reports of subjective caffeine effects are also suspect because of their failure to control for the increased probability of Type I error.

Adult

Otitis media in adult trauma patients: incidence and clinical significance.

To determine the incidence and clinical significance of otitis media in traumatized adults requiring intubation, 67 adult trauma patients admitted to a level-I trauma center over a 6-month period who required three or more days of intubation were examined otoscopically for the presence of otitis media. Eleven of these intubated brain-injured patients had otitis and upon examination all were found to have purulent paranasal sinusitis as well. In conclusion, all intubated patients with severe head injuries should be evaluated otoscopically for the presence of otitis and those patients with otitis should be examined for the presence of sinusitis.

Acute Disease

Sleep in acromegaly before and after treatment with adenomectomy.

Daytime somnolence and fatigue are frequently ignored symptoms in acromegaly. To examine whether sleep apnea or other abnormalities in the sleep structure is the underlying cause, 9 young patients with active untreated acromegaly for 2-7 years were studied with all night polysomnography. It revealed a decrease in REM sleep time in all the acromegalics compared to age- and sex-matched normal subjects (p less than 0.001) and also a reduction in delta sleep (p less than 0.05). None had obstructive sleep apnea. At reexamination 12-15 months posttreatment the daytime sleepiness had disappeared in all patients. REM sleep time increased in all patients (p less than 0.001) to normal level; delta sleep time increased moderately (p less than 0.05). Thus sleepiness in patients with high fasting level of growth hormone (GH) is not related to sleep apnea but more likely to a reduced amount of REM sleep time. By normalizing the GH concentration, REM sleep time became normal and the daytime sleepiness disappeared in all patients.

Acromegaly

Diagnosis, treatment and outcome of parathyroid cancer. A report of eight patients.

Eight patients presented parathyroid cancer between 1963 and 1990. There were seven women and one man with a median age of 55.5 years (range 34-81). At admission the median serum calcium concentration was 3.75 mmol/l (range 3.0-5.0), and four patients presented with a hypercalcaemic crisis. Six patients had a pathological bone resorption and five had reduced kidney function or urinary stones. All cases were treated by en bloc resection of the tumour and affected adjacent structures. One patient with a local lymph node metastasis died after seven months, and one in whom it was impossible to remove the tumour died after 14 months. Two patients had recurrences three and nine years after the operation, respectively. The first was treated with mithramycin, but died 33 months later, the other was reoperated on and was still normocalcaemic 2-9 years after diagnosis.

Adult

Microvascular density, microvascular surface area and endocrine cell volume in pituitary transplants to the fourth ventricle of adult rats.

Pituitary gland endocrine tissue was transplanted to the fourth ventricle of the brain of adult rats. The grafts were left in place for eight to ten weeks. One micron thick Epon sections were cut for microscopical and morphometrical analysis. The microvascular length density, the microvascular surface area density and the volume weighted mean pituitary cell volume were measured. The transplants were connected to the recipient brains through a few rather large vessels vessels either from the arachnoidea or the choroid plexus. Neuronal connections were never established. The microvascular length and surface area densities were significantly increased in the grafts, whereas the weighted mean cell volume was reduced. The results indicate that pituitary tissue can be transplanted to the fourth ventricle of the brain and the blood supply reestablished. The increased vascular densities are due to lower cell volume and probably also to cell loss and not to proliferation or angiogenesis. The reduced pituitary cell volume may be the result of missing trophic factors which normally are secreted to the pituitary in the sella turcica.

Animals

How to become involved in EDS.

This article presents ways in which dental students may become involved in EDS. It is important that EDS has the support of dental students as it is a Committee which works in their interest.

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