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Biomedical subjects

K L Jensen

Publications and source records attributed to K L Jensen.

At least 19 recordsLinked to original sources

New results in the theory of Fowler-Nordheim plots and the modelling of hemi-ellipsoidal emitters.

This paper reports further progress in understanding the theory of emission-area extraction from Fowler-Nordheim plots, and reports some useful interim results derived by modelling field electron emission from hemi-ellipsoidal emitters. The mathematical nature of the relationship between a new approach to emission-area extraction, recently proposed, and older approaches is demonstrated. The new approach is extended to cover field dependence in emission area. Preliminary results are reported from an investigation into the effects of making erroneous assumptions about the tunnelling barrier seen by the electron and the absence of field dependence in emission area. If wrong theoretical assumptions are made, then emission area can be overpredicted by a factor of as much as 10 or 20. On the other hand, if correct theoretical assumptions are made, then the extracted emission area is close to an emission area derived directly from the model calculations. The problematical nature of the concept of emission area, when emission area is a function of field, is pointed out.

Journal Article↗

Enhanced antiviral effect in cell culture of type 1 interferon and ribozymes targeting HCV RNA.

We have recently shown that the replication of an HCV-poliovirus (PV) chimera that is dependent upon the hepatitis C virus (HCV) 5' untranslated region (UTR) can be inhibited by treatment with ribozymes targeting HCV RNA. To determine the antiviral effects of anti-HCV ribozyme treatment in combination with type 1 interferon (IFN), we analysed the replication of this HCV-PV chimera in HeLa cells treated with anti-HCV ribozyme and/or IFN-alpha2a, IFN-alpha2b, or consensus IFN. The anti-HCV ribozyme, or any of the IFNs alone have significant inhibitory effects on HCV-PV replication compared to control treatment (> or = 85%, P < 0.01). The maximal inhibition due to IFN treatment (94%, P < 0.01) was achieved with > or = 50 U/ml for either IFN-alpha2a or IFN-alpha2b compared to control treatment. A similar level of inhibition in viral replication could be achieved with a 5-fold lower dose of IFN if ribozyme targeting the HCV 5' UTR was given in combination. For consensus IFN, the dose could be reduced by > 12.5-fold if ribozyme targeting the HCV 5' UTR was given in combination. Conversely, the dose of ribozyme could be reduced 3-fold if given in combination with any of the IFN preparations. Moreover, treatment with low doses (1-25 U/mL) of IFN-alpha2a, IFN-alpha2b, or consensus IFN in combination with anti-HCV ribozyme resulted in > 98% inhibition of HCV-PV replication compared to control treatment (P < 0.01). These results demonstrate that IFN and ribozyme each have a beneficial antiviral effect that is augmented when given in combination.

Animals↗

The effects of selected classical music on self-disclosure.

A cognitive theory of emotion and aesthetics in music suggests that listening to music is cognitively and in turn emotionally arousing. In addition a theory of inhibition and psychosomatic disease suggests that disclosing personal and traumatic information is psychologically and physically beneficial. This study examined the effect of music within a disclosure setting on the use of cognitive and emotional language in 85 undergraduates. Participants in both the background music and no music conditions wrote or spoke into a tape recorder, about the most significant event or experience of their lives. In addition to language, self-reported moods, subject impressions about the disclosure experience, and the environment were examined. Results indicate that background music had an effect on the disclosure topics chosen, promoted cognitive suggestion and expression, and increased the enjoyment of listening to classical music.

Adult↗

Inhibition of hepatitis C virus (HCV)-RNA-dependent translation and replication of a chimeric HCV poliovirus using synthetic stabilized ribozymes.

Ribozymes are catalytic RNA molecules that can be designed to cleave specific RNA sequences. To investigate the potential use of synthetic stabilized ribozymes for the treatment of chronic hepatitis C virus (HCV) infection, we designed and synthesized hammerhead ribozymes targeting 15 conserved sites in the 5' untranslated region (UTR) of HCV RNA. This region forms an internal ribosome entry site that allows for efficient translation of the HCV polyprotein. The 15 synthetic ribozymes contained modified nucleotides and linkages that stabilize the molecules against nuclease degradation. All 15 ribozymes were tested for their ability to reduce expression in an HCV 5' UTR/luciferase reporter system and for their ability to inhibit replication of an HCV-poliovirus (HCV-PV) chimera. Treatment with several ribozymes resulted in significant down-regulation of HCV 5' UTR/luciferase reporter expression (range 40% to 80% inhibition, P <.05). Moreover, several ribozymes showed significant inhibition (>90%, P <.001) of chimeric HCV-PV replication. We further show that the inhibitory activity of ribozymes targeting site 195 of HCV RNA exhibits a sequence-specific dose response, requires an active catalytic ribozyme core, and is dependent on the presence of the HCV 5' UTR. Treatment with synthetic stabilized anti-HCV ribozymes has the potential to aid patients who are infected with HCV by reducing the viral burden through specific targeting and cleavage of the viral genome.

Antiviral Agents↗

Randomised clinical trials in the Scandinavian Journal of Rheumatology.

OBJECTIVE: To identify all reports of randomised clinical trials in the Journal and compare our findings with reports available in Medline. METHODS: We handsearched the Scandinavian Journal of Rheumatology with supplements for the years 1955-1997 to identify reports of randomised clinical trials and controlled clinical trials. RESULTS: We identified 445 trial reports. In Medline, 134 of these trials (30%) were indexed as randomised or controlled trials; an additional 50 trials (11%) were available in Medline but were indexed differently. Thus, 261 of the trials (59%) we identified were not indexed in Medline; most of these trials were published in supplements to the Journal. CONCLUSION: Handsearching of medical journals for randomised trials can be a worthwhile effort. Clinicians and patients will become better informed about the value of different treatment options and researchers will reduce their risk of performing trials that are unnecessary.

Humans↗

Antitumor and antimetastatic activity of ribozymes targeting the messenger RNA of vascular endothelial growth factor receptors.

Chemically stabilized hammerhead ribozymes are nuclease-resistant, RNA-based oligonucleotides that selectively bind and cleave specific target RNAs. Due to their potential for specifically inhibiting gene expression, ribozymes are being investigated for therapeutic applications as well as for the elucidation of gene function. In particular, we have investigated ribozymes that target the mRNA of the vascular endothelial growth factor (VEGF) receptors because VEGF signaling is an important mediator of tumor angiogenesis and metastasis. Here we report pharmacodynamic studies testing anti-Flt-1 (VEGFR-1) and anti-KDR (VEGFR-2) ribozymes in animal models of solid tumor growth and metastasis. Ribozymes targeting either Flt-1 or KDR significantly inhibited primary tumor growth in a highly metastatic variant of Lewis lung carcinoma. However, only treatment with the anti-Flt-1 ribozyme resulted in a statistically significant and dose-dependent inhibition of lung metastasis in this model. The anti-Flt-1 ribozyme was then tested in a xenograft model of human metastatic colorectal cancer in which significant inhibition of liver metastasis was observed. Taken together, these data represent the first demonstration that synthetic ribozymes targeting VEGF receptor mRNA reduced the growth and metastasis of solid tumors in vivo.

Animals↗

Widespread occurrence of a highly conserved RING-H2 zinc finger motif in the model plant Arabidopsis thaliana.

Several novel Arabidopsis thaliana proteins containing a RING-H2 zinc finger motif were predicted after database searches. Alignment of 29 RING-H2 finger sequences shows that the motif is strikingly conserved in otherwise unrelated proteins. Only short, non-conserved polar/charged sequences distinguish these domains. The RING-H2 domain is most often present in multi-domain structures, a number of which are likely to contain a membrane-spanning region or an additional zinc finger. However, there are several small (126-200 residues) proteins consisting of an N-terminal domain, rich in aliphatic residues, and a C-terminal RING-H2 domain. Reverse-transcription PCR suggests that the RING-H2 genes are widely expressed at low levels.

Amino Acid Sequence↗

Phosphoinositide 3-kinase activity is necessary for insulin-dependent inhibition of apolipoprotein B secretion by rat hepatocytes and localizes to the endoplasmic reticulum.

Insulin inhibits apolipoprotein B (apoB) secretion by primary rat hepatocytes through activation of phosphoinositide 3-kinase (PI 3-K). Current studies demonstrate that the PI 3-K inhibitor wortmannin inhibits both basal and insulin-stimulated PI 3-K activities. Wortmannin and LY 294002, two structurally distinct PI 3-K inhibitors, prevent insulin-dependent inhibition of apoB secretion in a dose-dependent manner. To link PI 3-K activation to insulin action on apoB, we investigated whether insulin induced localization of activated PI 3-K to the endoplasmic reticulum (ER), where apoB biogenesis is initiated. Insulin action results in a significant redistribution of PI 3-K to a low density microsome (LDM) fraction containing apoB protein and apoB mRNA. Insulin stimulates a significant increase in PI 3-K activity associated with insulin receptor substrate-1 as well as an increase in insulin receptor substrate-1/PI 3-K mass in LDM. Subfractionation of LDM on sucrose density gradients shows that insulin significantly increases the amount of PI 3-K present in an ER fraction containing apoB. Insulin stimulates PI 3-K activity in smooth and rough microsomes isolated from rat hepatocytes, the latter of which contain rough ER as demonstrated by electron microscopy. Studies indicate that 1) PI 3-K activity is necessary for insulin-dependent inhibition of apoB secretion by rat hepatocytes; 2) insulin action leads to the activation and localization of PI 3-K in an ER fraction containing apoB; and 3) insulin stimulates PI 3-K activity in the rough ER.

Androstadienes↗

[Randomized clinical trials in the Ugeskrift for Laeger 1948-1995].

The Danish Medical Journal (Ugeskrift for Laeger) was handsearched for randomised and pseudorandomised clinical trials over the years 1948-1995. We found 665 trials of which 539 (81%) were classified as randomised; the randomisation method was not stated for 422 of them (78%) and was insufficiently described in the majority of the rest. This problem became worse with time (p = 0.01). In contrast to the international literature where the increase was more gradual and occurred several years later, the number of randomised trials increased markedly around 1973. This change is associated with the introduction of courses in clinical research methodology during the previous years. Since randomisation is the most important safeguard against bias, the method should be described in detail.

Clinical Trials as Topic↗

Delayed primary repair of a kyrogenic spinal accessory nerve injury: a case report.

The course of the accessory nerve through the posterior cervical triangle is superficial and in close juxtaposition to the posterior cervical lymph node chain. These anatomic features contribute to the common occurrence of kyrogenic injury to the accessory nerve. Unfortunately, the diagnosis of this injury often is delayed because the clinical presentation may mimic shoulder impingement or adhesive capsulitis. The authors present a case with a 15-year followup of a 48-year-old woman who underwent successful delayed primary repair of an accessory nerve injury after a lymph node biopsy. Electromyographic examination is recommended at 3 weeks after a suspected accessory nerve lesion, and if evidence of trapezial denervation is present, early surgical exploration is indicated because spontaneous recovery is rare.

Accessory Nerve Injuries↗

Transvaginal ultrasound, endometrial cytology sampled by Gynoscann and histology obtained by Uterine Explora Curette compared to the histology of the uterine specimen. A prospective study in pre- and postmenopausal women undergoing elective hysterectomy.

BACKGROUND: The purpose of this study was to evaluate the diagnostic value of transvaginal ultrasound measurement of endometrial thickness, cytology obtained by Gynoscann, and histology of the endometrium sampled by Uterine Explora Curette compared with histology of the uterine specimen as the gold standard. METHODS: Consecutive patients admitted for hysterectomy had transvaginal ultrasound, sampling by Gynoscann, and Uterine Explora Curette done just before surgery, after informed consent. RESULTS: A total of 181 women entered the study. Sixteen had endometrial cancer, seven had atypical hyperplasia and nine had complex hyperplasia. A total of 168 patients had a transvaginal ultrasound done. At a cutoff limit of 4mm (endometrial thickness of 4mm or less indicating normal endometrium), the sensitivity was 90.3%, the specificity 24.8%, the positive predictive value 21.4% and the negative predictive value 91.9%. One endometrial cancer, one atypical and one complex hyperplasia were missed. The Gynoscann method showed a sensitivity of 62.5%, a specificity of 94.0%, a positive predictive value of 69.0% and a negative predictive value of 92.1%. Two cancers, three atypical and six complex hyperplasia were missed. The Uterine Explora Curette showed a sensitivity of 90.6%, a specificity of 100.0%, a positive predictive value of 100.0% and a negative predictive value of 98.0%. One endometrial cancer and two complex hyperplasia were missed. CONCLUSION: Transvaginal ultrasound is a reliable method in excluding endometrial pathology. The Uterine Explora Curette was superior to Gynoscann in diagnosing neoplasia of the endometrium. It was found to have the same diagnostic accuracy as conventional dilatation and curettage.

Adult↗

A comparison of three-dimensional computed tomography scans and stereolithographic models for evaluation of craniofacial anomalies.

PURPOSE: This article describes the use of stereolithographic (SL) models as an adjunct to treatment planning in patients with Apert's syndrome, scaphocephaly, brachycephaly, and turricephaly. PATIENTS AND METHODS: Four syndrome patients had computed tomography (CT) scans done presurgically, and one of these patients was additionally scanned postoperatively. SL models and three-dimensional (3D) CT image reconstructions were produced from the CT data, and linear measurements were compared between the two modalities. RESULTS: All cases showed mean differences between measurements with 3D-CT and SL models of -0.3 to 0.8 mm, except on the CT scans with a gantry tilt (-1.7 mm) and the brachycephalic patient in whom larger deviations were demonstrated (-9.5 mm). CONCLUSION: The results of the study indicate that the accuracy of the SL technique is not always sufficient, necessitating additional validation studies before it can be recommended for routine clinical use.

Acrocephalosyndactylia↗

Proximal humeral reconstruction after excision of a primary sarcoma.

From 1978 to 1991, 19 patients underwent wide resection of the proximal humerus for a primary bone tumor. Reconstructions included intercalary autoclaved autograft and Neer prosthesis composites in 11 patients, intercalary allograft and Neer prosthesis composites in 4 patients, and a Neer prosthesis with methylmethacrylate in 4 patients. All patients were observed for at least 2 years or until death. The functional results and complications of the 19 procedures were evaluated. Function was rated as excellent for 17 patients and good for 2 patients. There were no failures of fixation. Local recurrence occurred in 2 patients. There were 2 cases of recurrent anterior subluxation and 1 of dislocation. Two superficial wound infections were treated successfully with local debridement and antibiotics. The authors conclude that autoclaved autograft or allograft when combined with a long-stem cemented Neer prosthesis offers an excellent composite for proximal humeral reconstruction.

Adolescent↗

Type II collagen is transiently expressed during avian cardiac valve morphogenesis.

We present new evidence of the temporal and spatial expression of type II collagen in the embryonic chick heart during the very early stages of its development. In particular, we emphasize the distribution of its mRNA and protein during valve formation. Type II collagen as well as several other fibrillar collagens (types I, III, and V) are present in stage 18 endocardial cushion mesenchymal cells. At stage 23, alpha 1 (II) collagen transcripts and the cognate polypeptide colocalize in the atrioventricular valves. As development proceeds, the relative abundance of alpha 1 (II) collagen transcripts decreases during the stages studied (stages 22 to 45; day 3.5 to day 19) as assayed by RNA blotting of extracts of whole hearts. Type II collagen protein was immunologically undetectable in stage 38 (day 12) hearts, although collagens I, III, and V persisted and localize in the valve regions, in the endothelial lining of the heart, and in the epicardium. In keeping with other observations of type II collagen expression in non-chondrogenic regions of a variety of vertebrate embryos, the avian heart also exhibits transient type II collagen expression.

Animals↗

Myogenic cytodifferentiation of the precardiac mesoderm in the rat.

The contractile cells of the primitive heart are derived from a subpopulation of the lateral plate splanchnic mesoderm. While the formation of the cardiac primordia has been studied in the avian embryo, little is known about this cell population in the mammal. To investigate the distribution and cellular differentiation of the myocardial precursors in the early mammalian embryo, we studied the sequential immunohistochemical appearance of desmin and myosin in whole mounts of rat embryos from the presomite (gestational day 9) through the 6-8 somite, straight heart tube (gestational day 10) stages of early cardiac morphogenesis. In contrast to the chicken, and previous reports in the mouse, our results show that myogenic differentiation of the muscle precursor cells of the heart begins in the presomite embryo prior to formation of the anterior intestinal portal or foregut. In addition, this cell population of the precardiac mesoderm appears as a single crescent-shaped population of cells in continuity across the midline which extends caudally during development and then fuses in the midline to form the primitive heart tube. Unlike skeletal myogenesis, desmin and myosin appear simultaneously and are codistributed throughout this initial period of heart development. These results suggest that myocardial differentiation in the rat is precocious when compared to the chicken and precedes the morphogenetic processes involved in formation of the primitive heart tube. Furthermore, this study provides the first description in the mammal of the spatial distribution of the myogenic precardiac mesoderm.

Animals↗