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Biomedical subjects

J L Hansen

Publications and source records attributed to J L Hansen.

At least 19 recordsLinked to original sources

Stability balloon for two-dimensional vortex ripple patterns.

Patterns of vortex ripples form when a sand bed is subjected to an oscillatory fluid flow. Here we describe experiments on the response of regular vortex ripple patterns to sudden changes of the driving amplitude a or frequency f. A sufficient decrease of f leads to a "freezing" of the pattern, while a sufficient increase of f leads to a supercritical secondary "pearling" instability. Sufficient changes in the amplitude a lead to subcritical secondary "doubling" and "bulging" instabilities. Our findings are summarized in a "stability balloon" for vortex ripple pattern formation.

Journal Article↗

[Visits to hospital emergency departments after restricted-admission changes at the Rigshospitalet].

INTRODUCTION: The aim of this study was to describe changes in the use of accident and emergency departments in the Copenhagen Hospital Co-operation after restricted admittance to the accident and emergency department at a large Danish university hospital, Rigshospitalet (admittance only for patients transported by ambulance or presenting with a referral from a doctor). MATERIAL AND METHODS: A retrospective study compared the number of patients treated in two periods, 1.7.1998 to 30.6.1999 and 1.7.1999 to 30.6.2000. Additional patient data were collected for the periods 1.7.1998 to 31.12.1998 and 1.7.1999 to 31.12.1999. RESULTS: A 4% decrease was seen in the total number of patients treated at the accident and emergency departments. The decrease in the number of patients treated at the accident and emergency department at Rigshospitalet was 69%, whereas the accident and emergency department at Bispebjerg Hospital experienced a 53% rise. DISCUSSION: The study showed good compliance in the local population after the restricted admittance to an accident and emergency department at a large university hospital. An expected total fall in the number of patients treated at the accident and emergency departments in the Copenhagen Hospital Co-operation could not be documented.

Adolescent↗

Structure and low-temperature thermal relaxation of ion-implanted germanium.

The structure of implantation-induced damage in Ge has been investigated using high resolution extended X-ray absorption fine structure spectroscopy (EXAFS). EXAFS data analysis was performed with the Cumulant Method. For the crystalline-to-amorphous transformation, a progressive increase in bond-length was observed without the presence of an asymmetry in interatomic distance distribution (RDF). Beyond the amorphization threshold the RDF was dose dependent and asymmetric, where the bond-length and asymmetry increased as functions of ion dose. Such an effect was attributed to the formation of three- and five-fold coordinated atoms within the amorphous phase. Low-temperature thermal annealing resulted in structural relaxation of the amorphous phase as evidenced by a reduction in the centroid, asymmetry and width of the RDF, as consistent with a reduction in the fraction of non four-fold coordinated atoms. The results have been compared to other EXAFS studies of amorphous Ge, and it is suggested that the range of bond-lengths reported therein is related to the sample preparation method and state of relaxation.

Journal Article↗

Functional reconstitution of the angiotensin II type 2 receptor and G(i) activation.

On the basis of the patterns of conserved amino acid sequence, the angiotensin II type 2 (AT(2)) receptor belongs to the family of serpentine receptors, which relay signals from extracellular stimuli to heterotrimeric G proteins. However, the AT(2) receptor signal transduction mechanisms are poorly understood. We have measured AT(2)-triggered activation of purified heterotrimeric proteins in urea-extracted membranes from cultured COS-7 cells expressing the recombinant receptor. This procedure removes contaminating GTP-binding proteins without inactivating the serpentine receptor. Binding studies using [(125)I] angiotensin (Ang) II revealed a single binding site with a K(d)=0.45 and a capacity of 627 fmol/mg protein in the extracted membranes. The AT(2) receptor caused a rapid activation of alpha(i) and alpha(o) but not of alpha(q) and alpha(s), as measured by radioactive guanosine 5'-3-O-(thio)triphosphate (GTPgammaS) binding. Activation required the presence of activated receptors, betagamma, and alpha subunits. As a first step aimed at developing an in vitro assay to examine AT(2) receptor pharmacology, we tested a battery of Ang II-related ligands for their ability to promote AT(1) or AT(2) receptor-catalyzed G(i) activation. Two proteolytic fragments of Ang II, Ang III and Ang1-7, also promoted activation of alpha(i) through the AT(2) receptor. Furthermore, we found that [Sar(1),Ala(8)]Ang II is an antagonist for both AT(1) and AT(2) receptors and that CPG42112 behaves as a partial agonist for the AT(2) receptor. In combination with previous observations, these results show that the AT(2) receptor is fully capable of activating G(i) and provides a new tool for exploring AT(2) receptor pharmacology and interactions with G-protein trimers.

3T3 Cells↗

Implications of physical symmetries in adaptive image classifiers.

It is demonstrated that rotational invariance and reflection symmetry of image classifiers lead to a reduction in the number of free parameters in the classifier. When used in adaptive detectors, e.g. neural networks, this may be used to decrease the number of training samples necessary to learn a given classification task, or to improve generalization of the neural network. Notably, the symmetrization of the detector does not compromise the ability to distinguish objects that break the symmetry.

Artificial Intelligence↗

Structure of the RNA-dependent RNA polymerase of poliovirus.

BACKGROUND: The central player in the replication of RNA viruses is the viral RNA-dependent RNA polymerase. The 53 kDa poliovirus polymerase, together with other viral and possibly host proteins, carries out viral RNA replication in the host cell cytoplasm. RNA-dependent RNA polymerases comprise a distinct category of polymerases that have limited sequence similarity to reverse transcriptases (RNA-dependent DNA polymerases) and perhaps also to DNA-dependent polymerases. Previously reported structures of RNA-dependent DNA polymerases, DNA-dependent DNA polymerases and a DNA-dependent RNA polymerase show that structural and evolutionary relationships exist between the different polymerase categories. RESULTS: We have determined the structure of the RNA-dependent RNA polymerase of poliovirus at 2.6 A resolution by X-ray crystallography. It has the same overall shape as other polymerases, commonly described by analogy to a right hand. The structures of the 'fingers' and 'thumb' subdomains of poliovirus polymerase differ from those of other polymerases, but the palm subdomain contains a core structure very similar to that of other polymerases. This conserved core structure is composed of four of the amino acid sequence motifs described for RNA-dependent polymerases. Structure-based alignments of these motifs has enabled us to modify and extend previous sequence and structural alignments so as to relate sequence conservation to function. Extensive regions of polymerase-polymerase interactions observed in the crystals suggest an unusual higher order structure that we believe is important for polymerase function. CONCLUSIONS: As a first example of a structure of an RNA-dependent RNA polymerase, the poliovirus polymerase structure provides for a better understanding of polymerase structure, function and evolution. In addition, it has yielded insights into an unusual higher order structure that may be critical for poliovirus polymerase function.

Amino Acid Sequence↗

Local hyperthermia, radiation therapy, and chemotherapy in patients with local-regional recurrence of breast carcinoma.

We retrospectively reviewed the response rate and the acute and long-term toxicity of combined treatment using radiation therapy, hyperthermia, and chemotherapy in 29 patients with locally or regionally recurrent or advanced adenocarcinoma of the breast who completed at least 4 of the 6 prescribed hyperthermia treatments as part of a Phase I-II trial. Thirty-nine separate hyperthermia treatment fields were evaluated. Cisplatin alone or cisplatin with etanidazole or bleomycin was delivered just prior to hyperthermia once weekly. Hyperthermia was delivered to a target minimum tumor temperature of 43 degrees C +/- 0.5 for 60 min. Following hyperthermia, a 400 cGy fraction of radiation was given. The radiation fraction size on other days was 200 cGy. Twenty-two fields had previously been irradiated and 17 fields had not. Prior chemotherapy had been given in 24 of 29 patients (83%) and hormonal therapy given in 21 (72%). The median follow-up time is 10 months; 16/29 patients (55%) have died of disease. The overall complete response rate for all fields was 53%. Response rate was not related to any clinical factor, radiation dose, microwave or ultrasound technique, type of chemotherapy, or tumor temperatures, but the number of patients in the study population was small. A statistically significant association between the likelihood of complications and the total radiation therapy dose (previous radiation and present radiation) was found. Persistent ulceration lasting greater than 1 month after completing treatment was seen in 67% of previously irradiated fields compared to 21% of fields that had not been previously treated (p = 0.015). Surgical wound repair was needed for 38% of fields with a history of prior irradiation versus 6% of those without prior treatment (p = 0.050). A statistically significant radiation therapy dose response was found for the likelihood of these complications. None of the hyperthermia temperature parameters studied correlated with an increased risk of complication. We conclude that the combination of radiation therapy, hyperthermia, and chemotherapy results in a high rate of complete response. However, in patients who have been treated with prior radiation therapy, this combination may be more locally toxic than treatment with hyperthermia and radiation therapy alone. The precise impact of chemotherapy on the therapeutic index of hyperthermia and radiation therapy remains to be determined in randomized clinical trials.

Adenocarcinoma↗

Rescue angioplasty during myocardial infarction has a beneficial effect on mortality: a tenable hypothesis.

HYPOTHESIS: Rescue percutaneous transluminal coronary angioplasty (PTCA) reduces mortality during myocardial infarction. OBJECTIVE: To determine if PTCA after failed thrombolytic therapy results in reduced mortality. DESIGN: Twenty-eight patients with a persistently occluded infarct artery following thrombolytic therapy more than 3 h after symptom onset were randomized to rescue PTCA (n = 16) or conservative treatment (n = 12) as part of a prospective randomized trial of reperfusion therapy during myocardial infarction in 184 patients. Hospital mortality was assessed in these groups as well as in the 177 patients with known infarct artery status after initial attempts at reperfusion. MAIN RESULTS: There was one death among the 16 patients in the rescue PTCA group versus four deaths in the 12 patients treated conservatively (P = 0.13). Moreover, the death in the rescue PTCA group occurred in one of three patients in whom the procedure failed. Mortality in the entire study group was 10.3% (19 of 184); 4.2% (six of 142) in patients in whom patency was achieved after thrombolysis and/or PTCA and 34.3% (12 of 35) in those in whom reperfusion was not achieved (P less than 0.001). In patients with anterior myocardial infarction, mortality was 6.7% (four of 60) in those with reperfusion and 47.1% (eight of 17) in those with a persistently occluded artery (P less than 0.001). In patients with inferior myocardial infarction, 2.4% (two of 82) with reperfusion and 22.2% (four of 18) with a persistently occluded artery died (P less than 0.01). CONCLUSIONS: Although the number of patients in the randomized groups was small, the trend toward a lower mortality after rescue PTCA supports the hypothesis that rescue PTCA may be beneficial. The mortality results in relation to presence or absence of reperfusion from the entire study population underscores the importance of achieving patency during myocardial infarction.

Aged↗

Relation between flow grade after thrombolytic therapy and the effect of angioplasty on left ventricular function: a prospective randomized trial.

Recent intervention trials during myocardial infarction demonstrated no benefit from emergency angioplasty after thrombolytic therapy when compared with either delayed percutaneous transluminal coronary angioplasty (PTCA) or a conservative strategy. However, it is possible that subgroups of patients may benefit from early intervention with angioplasty. We performed a prospective randomized trial in patients with a patent infarct-related artery after thrombolytic therapy to determine whether initial flow grade is related to infarct-zone function and whether patients with ineffective reperfusion (greater than 90% stenosis or Thrombolysis in Myocardial Infarction [TIMI] flow less than or equal to 2) might benefit from immediate PTCA. Thrombolytic therapy was administered to 170 patients at a mean of 2.1 +/- 0.5 hours after onset of myocardial infarction. A patent infarct-related artery that was suitable for angioplasty was present in 89 patients who comprised the study group; after randomization, 47 of 50 patients with a patent infarct-related artery had successful emergency PTCA 3.8 +/- 1.5 hours after onset of symptoms, and 39 were scheduled for delayed (18 to 48-hour) PTCA. Reocclusion occurred before the scheduled (delayed) procedure in eight patients (20.5%), and was symptomatic in six. Infarct-region function (by the centerline method) measured initially, before discharge, and at 4 months was similar in both groups; improvement was significant (p less than 0.001) at discharge when compared with initial values with no further change at 4 months. However, patients with ineffective reperfusion had greater hypokinesia initially (p less than 0.05) compared with those with effective reperfusion (less than or equal to 90% stenosis plus TIMI flow 3). Moreover, independent of the timing of PTCA, improvement was greater before discharge in patients with ineffective reperfusion (p less than 0.05) with a trend also evident at 4 months. Importantly, 42 of 51 patients (82%) with a residual lumen less than 0.4 mm after thrombolysis had some improvement in function at discharge; this compared with a previous study in which patients with a similar degree of stenosis (without PTCA) had no improvement. Moreover, reocclusion occurred before scheduled (delayed) PTCA in 37% of patients with greater than 90% stenosis compared with only 5% in those with less than or equal to 90% stenosis (p = 0.02). Thus flow grade is an important determinant of myocardial function in patients with a patent artery after thrombolytic therapy and is predictive both of improvement in wall motion after PTCA and early reocclusion.(ABSTRACT TRUNCATED AT 400 WORDS)

Angioplasty, Balloon, Coronary↗

Effect of short-term prostacyclin administration on restenosis after percutaneous transluminal coronary angioplasty.

The effect of short-term prostacyclin (PGI2) administration on the incidence of restenosis after coronary angioplasty was studied in a prospective single-blind randomized trial of 286 patients. Of the 270 patients in whom dilation was successful, 134 received prostacyclin and 136 received placebo. Intracoronary prostacyclin was administered before and after dilation and then intravenously for 48 h. The control group received intracoronary placebo infusions before and after dilation. All patients received aspirin and dipyridamole before and after angioplasty, at least until follow-up angiography. Follow-up angiograms were obtained in 93% of patients in whom angioplasty was successful. Restenosis of one or more lesions was present in 34 patients (27%) who were given prostacyclin compared with 40 patients (32%) in the control group (p = NS). Acute vessel closure and ventricular tachyarrhythmias were more common in the control group than in the patients who received prostacyclin (acute vessel closure occurred in 14 [10.3%] of 136 versus 4 [3.0%] of 134, respectively, p less than 0.01; ventricular tachyarrhythmias occurred in 5 [3.4%] of 147 versus 0 of 139 respectively, p less than 0.05). Short-term administration of prostacyclin did not significantly lower the risk of restenosis after coronary angioplasty.

Aged↗

Neonatal hemochromatosis. Genetic analysis of transferrin-receptor, H-apoferritin, and L-apoferritin loci and of the human leukocyte antigen class I region.

Neonatal hemochromatosis (NH), a generally fatal disorder of infancy, is characterized by severe hepatic insufficiency of intrauterine onset and by marked organ iron loading. Its cause is unknown. It has been suggested that NH may represent an unusual manifestation of hereditary hemochromatosis (HH), which is human leukocyte antigen (HLA) linked. Evidence for major rearrangements or deletions at the HLA class I region and at three loci directly involved in iron metabolism (H- and L-apoferritin and the transferrin receptor [TfR]) was sought. The population studied included five probands with NH and 14 first-degree family members in a total of six kindreds. Also sought were HLA associations with NH by collating the results of HLA serotyping in these 19 persons and in 17 members of 7 additional kindreds in which NH has occurred, including 5 probands with NH and 12 first-degree family members. We found no evidence for major rearrangements or deletions in H- or L-apoferritin genes, in TfR genes, or within the HLA locus. We found no evidence for linkage of NH to HLA serotypes. We conclude that while NH and HH are similar in their patterns of iron loading, they are not genetically related.

Adult↗

The HLA class I locus: analysis of RFLPs in hereditary hemochromatosis.

The gene for hereditary hemochromatosis is linked to the HLA locus on chromosome 6. Four cloned DNA probes originating from the HLA class I region were used to detect seven restriction fragment length polymorphisms (RFLPs). Allele frequencies and segregation of each RFLP was determined. Analysis of RFLPs in 38 unrelated homozygotes with hemochromatosis revealed differences in allele frequencies between the control and the hemochromatotic groups but these differences did not reach statistical significance. Some differences persisted, however, even when only controls with the A3 antigen were compared with A3 hemochromatotics. Since both control and hemochromatotic groups were small, further studies will be necessary to ascertain whether these RFLPs could serve to locate the gene responsible for hereditary hemochromatosis.

Adult↗

A point mutation in the coding region of uroporphyrinogen decarboxylase associated with familial porphyria cutanea tarda.

Familial porphyria cutanea tarda (PCT) is inherited as an autosomal dominant trait caused by decreased activity of uroporphyrinogen decarboxylase (URO-D). In most families with PCT, URO-D mRNA levels are normal but both catalytic activity and immunologic reactivity of URO-D are half normal. We have cloned and sequenced 8 URO-D cDNA transcripts derived from a pedigree member with familial PCT. Three of the cDNAs had sequences encoding normal URO-D but five cDNA's contained a point mutation resulting in a gly----val substitution at amino acid position 281. An oligonucleotide probe complementary to the mutant sequence hybridized to DNA from affected individuals within the pedigree, but not to DNA from normal individuals. Measurements of pulse labeled URO-D in Epstein-Barr virus transformed lymphocytes indicated that the mutant protein has a half-life in vivo of less than four hours. In vitro measurements utilizing labeled URO-Ds generated in a reticulocyte lysate system revealed a 12-hour half-life for the mutant protein compared with a 102-hour half-life for normal URO-D. This is the first URO-D mutation to be characterized in a pedigree with familial PCT. This mutation was not detected in affected individuals from seven other PCT pedigrees, suggesting that PCT can result from different mutations.

Carboxy-Lyases↗

Radiosurgery for arteriovenous malformations of the brain using a standard linear accelerator: rationale and technique.

We have recently initiated a program for irradiating small, unresectable arteriovenous malformations (AVM's) in the brain. The treatments are delivered using a modified and carefully calibrated 6 MV linac. We are using high, single doses (15 to 25 Gy) with a goal of sclerosing the vessels and preventing hemorrhages. This technique, radiosurgery, is somewhat controversial in the radiotherapy community. Since the treatment is given in a single sitting, rather than in the more conventional pattern of multiple small daily fractions, there is some concern about late radiation damage to the normal brain tissue. However an extensive review of the literature leads us to the conclusion that if a technique is used that keeps the volume irradiated to high dose small, radiosurgery is a safe and efficacious treatment for small (less than 2.5 cm) AVM's. To decrease the risk of necrosis of normal brain tissue, it is important to confine the high dose region as tightly as possible to the target volume. Precise target localization and patient immobilization is achieved using a stereotactic head frame which is used during angiography, CT scanning, and during the radiation treatment. This minimizes the margin of safety that must be added to the target volume for errors in localization and set-up. The treatment is delivered using multiple noncoplanar arcs, with small, sharp edged X ray beams, and with the center of the AVM at isocenter. This produces a rapid dropoff of dose beyond the target volume. Early results in our first few patients are encouraging.

Humans↗

Steady-state levels of uroporphyrinogen decarboxylase mRNA in lymphoblastoid cell lines from patients with familial porphyria cutanea tarda and their relatives.

Familial porphyria cutanea tarda (PCT) results from a generalized deficiency of uroporphyrinogen decarboxylase (URO-D) activity. The molecular defect responsible for this disorder has not been characterized. To determine whether decreased levels of URO-D mRNA are responsible for subnormal URO-D activity, steady-state levels of URO-D mRNA in lymphoblastoid cells were determined. Northern blots were hybridized with a URO-D cDNA probe and quantified by densitometry. No difference in the levels of URO-D mRNA was detected between affected individuals and their normal relatives. Thus, the deficiency of URO-D activity in two familial PCT pedigrees characterized here does not arise from a deficiency of URO-D mRNA.

Carboxy-Lyases↗

A new system for patient fixation in radiotherapy.

A new system for patient fixation in radiation treatment is described. The system consists of an airtight plastic bag with a contents of polysterol microspheres. A valve allows evacuation which results in a rigid close fitting cast. The system was compared with conventional foam cast fixation in 29 patients who were treated for carcinoma of the breast. The patients received radiation treatment over 22 fractions, and portal X-ray pictures were obtained at every second treatment. The portal films were compared with the stimulator radiographs and the variation in the position of the centre cross were measured in cranio-caudal and transversal direction as well as the rotation of the centre cross. The results showed that the daily reproducibility of the patient set-up was considerably improved by the new system, the centre cross deviation of the position of the actual radiation field to the centre cross of the intended field being less than 1 mm in 50% of the cases. The system is time-saving and cheap compared to conventional fixation systems.

Breast Neoplasms↗