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Biomedical subjects

H J Jensen

Publications and source records attributed to H J Jensen.

At least 19 recordsLinked to original sources
PubMed2006

Astatinated trastuzumab, a putative agent for radionuclide immunotherapy of ErbB2-expressing tumours.

The anti-ErbB2 antibody trastuzumab is used for the treatment of patients with advanced breast cancer, resulting in a response rate of 40-60%. Coupling with a cytotoxic nuclide, e.g. alpha-emitting 211At, may further increase tumour response. The tumour-targeting properties of trastuzumab, astatinated using N-succinimidyl-para-(tri-n-methylstannyl)-benzoate, were evaluated and compared with those of radioiodinated trastuzumab in this study. We found that astatinated trastuzumab retains high specificity towards ErbB2. While the immunoreactive fraction of radioiodinated trastuzumab was higher than that of astatinated trastuzumab (76+/-9% versus 54+/-28%), both radioconjugates showed high affinity (KD 0.75+/-0.16 nM versus 1.8+/-0.3 nM). A growth inhibition study indicated a dose-dependent cell deactivation, in which approximately 74 cell-associated astatine decays per cell gave a survival fraction of 4.5+/-0.8x10(-4). Results of a comparative animal study on normal mice gave no indication that astatination would have any adverse effects on the biodistribution of the antibody. In conclusion, the results of the study suggest that astatinated trastuzumab is a promising candidate for treating ErbB2-expressing tumours.

Animals↗
PubMed2005

In vitro evaluation of the astatinated chimeric monoclonal antibody U36, a potential candidate for treatment of head and neck squamous cell carcinoma.

PURPOSE: The purpose of this study was to analyse the properties of the astatinated chimeric MAb (cMAb) U36 as a conjugate to selectively target and eradicate head and neck squamous cell carcinoma (HNSCC). METHODS: cMAb U36 was labelled with 211At via the linker N-succinimidyl 4-(trimethylstannyl)benzoate (SPMB). The quality of the conjugate was extensively evaluated for binding and internalisation capacity, and compared with 125I-SPMB-cMAb U36. The cellular toxicity of the astatinated conjugate was assessed in two types of in vitro growth assay and compared with 131I-labelled cMAb U36 (directly labelled). RESULTS: Comparisons between 211At-cMAb U36 and 125I-cMAb U36 demonstrated an optimal functional capacity of the labelled products. Immunoreactivity and affinity assays showed high immunoreactive fractions (>93%), and an affinity in good agreement between the astatinated and iodinated antibodies. For both conjugates, specific binding to HNSCC cells could be demonstrated, as well as some internalisation. Retention of the astatinated conjugate was just slightly lower than for the iodinated conjugate and still reasonable for therapeutic use (31+/-2% vs 42.6+/-1.0% at 22 h), demonstrating no adverse effects from astatination of the antibody. Studies on cellular toxicity demonstrated a dose-dependent and antigen-specific cellular toxicity for 211At-cMAb U36, with about 10% cell survival at 50 decays per cell. The 131I-labelled conjugate was not as efficient, with a surviving cell fraction of about 50% at 55 decays per cell. CONCLUSION: These results indicate that 211At-cMAb U36 might be a promising future candidate for eradicating HNSCC micrometastases in vivo.

Antibodies, Monoclonal↗
PubMed2001

Dry-distillation of astatine-211 from irradiated bismuth targets: a time-saving procedure with high recovery yields.

Astatine-211 was produced via the 209Bi(alpha,2n) 211At reaction. The radionuclide was isolated with a novel procedure employing dry-distillation of the irradiated target material. The astatine was condensed as a dry residue in a PEEK-capillary cryotrap. Distillation was completed within 1-2 min with isolation yields of 92 +/- 3%. Subsequent work-up of the nuclide resulted in final recovery yields of 79 +/- 3%.

Astatine↗
PubMed2000

Determination of the excitation function for the 10B(p,n)10C reaction with implications for the production of [10C]carbon dioxide for use as a PET tracer.

To evaluate the possibilities of producing useful amounts of 10C (T1/2 = 19 s) for use as an on-line, steady state positron emission tomography (PET) tracer, the excitation function and the thick target yield for the 10B(p,n)10C reaction up to 30 MeV were measured using an adapted version of the stacked-foil technique. The radionuclidic purity of the produced 10C versus the inevitable 11C contamination was evaluated as function of target thickness and incident proton beam energy.

Boron↗
PubMed1998

Working in regional health network.

This paper describes the conditions for, and actually use of telematics in a regional Health Network in a Danish county. This paper gives an introductory view over the organisation of the Danish health care system, and the general practitioners place in it. The advantages experienced and the actual use of telematics in general practice today is described. Finally, the expectations for the near future is mentioned.

Denmark↗
PubMed1997

On the critical behaviour of simple epidemics.

We show how ideas and models which were originally introduced to gain an understanding of critical phenomena can be used to interpret the dynamics of epidemics of communicable disease in real populations. Specifically, we present an analysis of the dynamics of disease outbreaks for three common communicable infections from a small isolated island population. The strongly fluctuating nature of the temporal incidence of disease is captured by the model, and comparisons between exponents calculated from the data and from simulations are made. A forest-fire model with sparks is used to classify the observed scaling dynamics of the epidemics and provides a unified picture of the epidemiology which conventional epidemiological analysis is unable to reproduce. This study suggests that power-law scaling can emerge in natural systems when they are driven on widely separated time-scales, in accordance with recent analytic renormalization group calculations.

Disease Outbreaks↗
PubMed1997

A serological indication of the existence of a guineapig poliovirus.

Attempts were made to clarify whether laboratory guineapigs may harbour a poliovirus which, in 1911, was described as the cause of a disease called guineapig lameness. By the use of ELISA for antibodies against the poliovirus, Theiler's murine encephalomyelitis virus (TMEV), it was shown that two pet shop guineapigs suffering from lameness had extremely high titres against poliovirus, while healthy guineapigs from the same pet shop were negative. Clearly positive results were also found in 35 out of 152 laboratory guineapig sera. Positive results were found in only two out of six breeding centres, but in three out of three experimental units, all of which purchased guineapigs from one of the seropositive breeding colonies. The diseased guineapigs recovered fully after treatment with vitamins in the drinking water, a treatment used for guineapig lameness by small animal practitioners. A theory that vitamin C deficient guineapigs are, due to an impaired steroid secretion, predisposed to succumbing to infection and develop demyelinating disease similar to that in TMEV infected mice is discussed briefly. Guineapig sera were also tested serologically for other infections. Antibodies against lymphocytic choriomeningitis virus, Clostridium piliforme and Toxoplasma gondii were not found, but one breeding colony was infected with adenovirus, pneumonia virus of mice, reovirus type 3, Sendai virus, parainfluenza (simian) virus type 5 and Encephalitozoon cuniculi. Two other breeding colonies were infected with both reovirus type 3 and E. cuniculi. In all three experimental units infection with adenovirus was observed, and in two of these Sendai virus and E. cuniculi antibodies were also found. The pet shop guineapigs were infected with adenovirus, reovirus type 3 and E. cuniculi.

Animals↗
PubMed1993

[Hysterosalpingography using iotrolan--a new contrast medium].

Iotrolan was investigated as a new contrast medium for hysterosalpingography. Fertility rates and side-effects were registered in a series of 108 consecutive patients. The results indicate a higher fertility rate after hysterosalpingography with iotrolan than after the use of other water-soluble contrast media but a lower fertility rate when compared to lipiodol. As for side-effects, the study indicates that the frequencies of low abdominal pain and vaginal bleeding after hysterosalpingography are equal for iotrolan and lipiodol but higher for other, water-soluble contrast media. A prospective, randomized study is recommended for the clarification of these aspects.

Abdominal Pain↗
PubMed1991

[Periventricular cerebral hemorrhage in children with very low birth weights in the county of North Jutland. Retrospective study].

The object of this investigation was to determine the frequency of intracerebral periventricular haemorrhage in neonates with very low birthweights in an unselected material from the County of North Jutland. During the years 1988-1989 a total of 86 infants with low birthweights were born in the county. Intracerebral periventricular haemorrhage was diagnosed by means of ultrasonic scanning of the cerebrum and/or postmortem examination. Seven infants had to be excluded as neither of these examinations had been performed. The material thus consisted of 79 infants with a median weight of 1,196 gram (range 565-1,500 g) and a median gestational age of 30 weeks (range 25-37 weeks). Periventricular haemorrhage was found in a total of 13 infants, corresponding to 16% and the haemorrhages were found mainly in infants with gestational ages less than or equal to 29 weeks (32%). Haemorrhages with involvement of the parenchyma and/or dilation of the ventricular system comprised more than half of the cases of haemorrhage (8 out 13). The frequency of periventricular haemorrhage fell with gestational ages less than or equal to 30 weeks and the haemorrhages were less extensive. The respiratory distress syndrome and asphyxia were found to important risk factors for the development of periventricular haemorrhage.

Cerebral Hemorrhage↗
PubMed1991

A new mouse mutant with progressive motor neuronopathy.

A new autosomal-recessive mouse mutant with progressive motor neuronopathy (pmn) is described. Homozygotes develop paralysis of the hindlimbs during the third week of life. Soon thereafter the forelimbs also become weak, and all mice die six to seven weeks after birth. Heterozygotes are normal. Skeletal muscles show neurogenic atrophy without histological signs of reinnervation. Axonal degeneration apparently starts at the endplates and is prominent in the sciatic nerve and its branches and the phrenic nerve. Axonal sprouts are abundant. There is no evidence of demyelination, and unaffected nerve fibers are normally myelinated. Sensory axons are spared. Almost all distal motor axons have disappeared in four to five weeks after birth. Ventral nerve roots show a reduced diameter of the largest fibers but no fiber deficits. The ventral horn cells show slight chromatolysis. The corticospinal tract is normal, but in terminally ill animals the fasciculus gracilis, the rubrospinal tract and possibly also reticulospinal fibers degenerate. The brain is histologically normal. The disease manifests itself in a dying-back fashion in the distal portion of the motor neurons and may represent an animal model of hereditary motor neuron diseases in man.

Animals↗
PubMed1982

Lactose malabsorption and tolerance of lactose-hydrolyzed milk. A double-blind controlled crossover study.

Eleven lactose-intolerant patients were investigated in a double-blind crossover controlled study. In random sequence they received 500 ml of either ordinary cow milk (lactose content, 25 g) or the same amount of low-lactose milk (85% of the lactose hydrolyzed), which had been processed by Lactozym 3000 L for 24 h at 4 degrees C. A significantly increased blood glucose rise from fasting levels was demonstrated in the low-lactose tests. Similarly, a significant reduction of liquid stool frequency, abdominal colics, distention, borborrhygmia, and flatulence was demonstrated. It was concluded that further studies, including long-term treatment of lactose-intolerant children, are indicated.

Adult↗
PubMed1980

System-theoretical analysis of the Clare Bishop Area in the cat.

The Clare Bishop Area (CBA) is a retinotopically organized cortical area in the cat brain connected to a great variety of visual areas in a very complex way (Fig. 1). Experimental analysis is difficult because of the following aspects: 1. As the distance from the retina increases, the signal combinations necessary to analyse the system become more and more specific. 2. Feedback loops cannot be opened, so an unequivocal identification of CBA cell properties is impossible. 3. The nonlinear character seems to have a great influence on signal processing. To circumvent these problems, specific signal combinations leading to a separation of input subsystems have been developed (Hoffmann and v. Seelen, 1979). On grounds of practical experience and theoretic considerations, the signal combinations are usually restricted to combinations of deterministic and stochastic signals when analysing the CBA. The different methods of measurement are applied successively, the linearizing ones being used first so that a rough classification is possible. If the nonlinear features of the system have little efect, they can be linearized in the theoretical description, if not, a model consisting of a sequence of a linear dynamic system and a nonlinear one with a static, polynomial feature must be used for analysis by parameter estimation. The experimental part of this publication deals with the determination of a number of cell properties. Some hypotheses on the function of the CBA are tested. THe results lead to the conclusion that further experiments, such as are discussed below, are necessary in the input subsystems, area 18 and 19. The experimental results of some other authors (Hubel and Wiesel, 1969; Turlejski, 1975; Turlejski and Michalski, 1975; Smith and Bauman, 1979; SPera and Bauman, 1979) are confirmed by the implicaions of the present results.

Animals↗
PubMed1980

On localization of moving objects in the visual system of cats.

In cortical areas direction-specific receptive fields occur systematically. Direction specifity is based on unsymmetric coupling of neurons. Such a coupling allows an exact localization of moved stimuli. For this task, the asymmetry in the time domain is compensated for by a spatial asymmetry.

Animals↗
PubMed1978

Enteric hyperoxaluria: dependence on small intestinal resection, colectomy, and steatorrhoea in chronic inflammatory bowel disease.

The importance of intestinal resection, exclusion of the colon, and steatorrhoea for secondary hyperoxaluria was studied in 81 patients with Crohn's disease and 12 patients with ileostomy after colectomy for ulcerative colitis during a metabolic regime including a fixed oral supply of fat, calcium, and oxalate. Hyperoxaluria (greater than 48 mg (greater than 0.5 mmol) per 24 h) was present in 21 patients with Crohn's disease. All but one half or more of the colon preserved. Renal oxalate excretion was related to the amount of ileum resected. 14C-oxalate absorption was significantly higher in patients with ileal resection and the whole colon preserved than in patients with ileal resection plus hemicolectomy, despite the fact that the latter group had the most extensive ileal resections. Faecal fat and oxalate excretion agreed well in patients without ileostomy (r = 0.76, p less than 0.001), and renal oxalate excretion was significantly higher in patients with steatorrhea and the colon preserved than in patients without steatorrhoea. In all 93 patients 14C-oxalate absorption and renal oxalate excretion was positively correlated with a coefficient of correlation of 0.76 (p less than 0.001). No correlation was present between 47Ca- and 14C-oxalate absorption. The study confirm that a preserved colon is necessary for secondary hyperoxaluria and stresses the importance of ileal resection and steatorrhoea.

Adult↗
PubMed1977

Electron microscopy of lymph nodes of hamsters experimentally infected with Treponema pertenue.

The morphology of lymph node tissue from normal hamsters and from hamsters experimentally infected with Treponema pertenue Gauthier was compared by means of light and electron microscopy. The capsules of the lymph nodes from infected hamsters showed an increased thickness in comparison with those of the non-infected animals. The infected lymph nodes differed from normal lymph nodes by small accumulations of neutrophilic leucocytes in the cortical areas. In addition, the amount of intercellular collagenous matrix present between large elongated cells was greatly increased in lymph nodes from infected animals. Electron microscopy of thin sections of infected lymph nodes showed intercellularly located treponemes in the leucocyte infiltration areas. These regions also showed the increased amounts of the collagenous matrix. Treponemes were occasionally found intracellularly in macrophages. These treponemes did not show their typically helical shape, but were present as spherical forms or cysts.

Animals↗