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Biomedical subjects

D Koch

Publications and source records attributed to D Koch.

At least 37 records · Page 2Linked to original sources

Lhermitte-Duclos disease: assessment with MR imaging, positron emission tomography, single-photon emission CT, and MR spectroscopy.

SUMMARY: Lhermitte-Duclos disease (LDD) is a rare cerebellar lesion with features of both malformation and benign neoplasm. However, the fundamental nature of the entity, its pathogenesis, and the exact genetic alterations remain unknown. We describe MR findings (including perfusion- and diffusion-weighted images) in two patients with LDD, as well as findings from single-photon emission CT (SPECT), MR spectroscopy (MRS), and fluorodeoxyglucose (FDG) positron emission tomography (PET) that give additional information about tumor pathophysiology. MR imaging usually distinguishes the LDD by its characteristic "tiger-striped" appearance. The regions of increased regional cerebral blood volume (rCBV) within the lesion correlated closely to the regions of FDG-hypermetabolism and high thallium (201-Tl) uptake. Proton MRS revealed an increased level of lactate and decreased level of myo-inositiol and N-acetyl-aspartate, as observed in low-grade gliomas, but decreased levels of choline. Our cases indicate that the functional investigations give additional information about tumor pathophysiology and reflect the histopathologic controversial entity with both characteristics found in low-grade gliomas and characteristics not typical for tumors.

Adult↗

An entirely humanized CD3 zeta-chain signaling receptor that directs peripheral blood t cells to specific lysis of carcinoembryonic antigen-positive tumor cells.

Recombinant T-cell receptors with antibody-like specificity for tumor-associated antigens are successfully used to direct the cytolytic activity of T cells toward tumor cells. Clinical application, however, needs to comply with the low immunogenicity of the recombinant receptor, efficient gene transfer into peripheral blood T cells, and enrichment of receptor-grafted cells. Here, we address these issues and describe an entirely humanized immune receptor for use in adoptive immunotherapy of colorectal carcinoma. The receptor consists of a single-chain antibody (scFv) binding domain specific for carcinoembryonic antigen (CEA), the IgG hinge and CH2/CH3 (Fc) joining region, and the transmembrane and intracellular CD3 zeta signaling chain. To express the receptor in peripheral blood T cells, both GALV envelope and MuLV 4070A pseudotyped retrovirus turned out to be equally efficient, with transduction efficiencies of about 5% to 40%, depending on the lymphocyte donor. Furthermore, receptor-grafted T cells could be 2- to 6-fold enriched by magnetic activated cell sorting, utilizing an antibody directed to the extracellular IgG domain of the receptor. Upon co-culture with CEA(+) tumor cells, receptor-grafted T cells are specifically and efficiently activated to cytolysis and IFN-gamma secretion, demonstrating their feasibility for the adoptive immunotherapy of CEA(+) carcinomas.

Antibody Specificity↗

Detection of Planetary Transits of the Star HD 209458 in the Hipparcos Data Set.

A search of the Hipparcos satellite photometry data for the star HD 209458 reveals evidence for a planetary transit signature consistent with the planetary properties reported by Henry et al. and Charbonneau et al. and allows further refinement of the planet's orbital period. The long time baseline (about 2926 days or 830 periods) from the best Hipparcos transit-like event to the latest transit reported by Henry et al. for the night of 1999 November 15 (UT) allows for an orbital period determination of 3.524736 days with an uncertainty of 0.000045 days (3.9 s). The transit events observed by Charbonneau et al. fall at the interim times expected to within the errors of this newly derived period. A series of statistical tests was performed to assess the likelihood of these events occurring by chance. This was crucial given the ill-conditioned problem presented by the sparse sampling of the light curve and the non-Gaussian distribution of the points. Monte Carlo simulations using bootstrap methods with the actual Hipparcos HD 209458 data set indicate that the transit-like signals of the depth observed would only be produced by chance in 21 out of 1 million trials. The transit durations and depths obtained from the Hipparcos data are also consistent with those determined by Charbonneau et al. and Henry et al. within the limitations of the sampling intervals and photometric precision of the Hipparcos data.

Journal Article↗

A chimeric receptor that selectively targets membrane-bound carcinoembryonic antigen (mCEA) in the presence of soluble CEA.

Chimeric T cell receptors with specificity for tumor-associated antigens are successfully used to target T cells to tumor cells. The efficacy of this approach, however, is reduced by soluble antigen that is frequently present in high serum concentrations. To overcome this situation, we constructed an anti-CEA chimeric receptor whose extracellular moiety is composed of a humanized single chain antibody fragment (scFv) derived from the anti-CEA mAb BW431/26 and the CH2/CH3 constant domains of human IgG. The intracellular moiety consists of the gamma-signaling chain of the human Fc epsilon RI receptor constituting a completely humanized chimeric receptor. After transfection, the humBW431/26 scFv-CH2CH3-gamma receptor is expressed as a homodimer on the surface of MD45 T cells. Co-incubation with CEA+ tumor cells specifically activates grafted MD45 T cells indicated by IL-2 secretion and cytolytic activity against CEA+ tumor cells. Notably, the efficacy of receptor-mediated activation is not affected by soluble CEA up to 25 micrograms/ml demonstrating the usefulness of this chimeric receptor for specific cellular activation by membrane-bound CEA even in the presence of high concentrations of CEA, as found in patients during progression of the disease.

Carcinoembryonic Antigen↗

Ongoing coding reviews: ways to ensure quality.

As compliance becomes an increasingly hot topic, how can a facility ensure its coding quality? Here are some ways that HIM departments can improve the quality of coding on a daily basis.

Abstracting and Indexing↗

Generation of the single chain antibody fragment conserves the idiotypic profile of the anti-CD30 monoclonal antibody HRS3.

Recombinant single chain antibody fragments (scFv) derived by combining immunoglobulin VL and VH regions provide valuable antibody-like reagents. A number of them are shown to have retained the antigen specificity of the parental monoclonal antibody (MoAb). Little is known about the idiotypic profile of scFv fragments compared with that of the parental MoAb. To address this question we analysed the idiotypic profile of a scFv that was derived by phage-display techniques from the anti-CD30 MoAb HRS3. We assayed (i) binding of HRS3-scFv to recombinant CD30-Fc antigen and to four different anti-idiotypic MoAbs defining at least three different idiotopes on HRS3, and (ii) cross-competition with the parental MoAb HRS3 and the closely related anti-CD30 MoAb HRS4. The assays revealed that the HRS3-scFv fragment exhibits the same specificity for both CD30 antigen and the tested anti-idiotypic MoAbs compared with the parental MoAb demonstrating that the recombinant scFv fragment has retained the complete idiotope of the parental MoAb.

Animals↗

Steric hindrance between chromophore substituents as the driving force of rhodopsin photoisomerization: 10-methyl-13-demethyl retinal containing rhodopsin.

A visual chromophore analogue, 10-methyl-13-demethyl (dm) retinal, was synthesized and reconstituted with bleached bovine rhodopsin to form a visual pigment derivative with absorbance maximum at 505 nm. The investigations with this new compound were stimulated from recent results using 13-dm retinal as a chromophore that revealed a remarkable loss in quantum efficiency (phi of 13-dm retinal-containing rhodopsin: 0.30, Ternieden and Gärtner, J. Photochem. Photobiol. B Biol, 33, 83-86, 1996). The quantum efficiency of the new pigment was determined as 0.59 by quantitative bleaching using reconstituted rhodopsin as a reference. The very similar quantum efficiencies of rhodopsin and the new pigment give experimental support for the recently presented hypothesis that a steric hindrance between the substituents at positions 10 and 13 in 11-cis-retinal is elevated during the photoisomerization and thus facilitates the rapid photoisomerization of the visual chromophore (Peteanu et al., Proc. Natl. Acad. Sci. USA 90, 11762-11766, 1993). Such steric hindrance is removed from the molecule by the elimination of the methyl group from position 13 and can be re-established via a rearrangement of the substitution pattern by introducing a methyl group at position 10 of 13-dm retinal.

Animals↗

[Multidisciplinary treatment program for chronic low back pain, part 2. Somatic aspects].

PROBLEM: There is a great need to expand current knowledge of the various functional capacity measurements used in the rehabilitation of chronic low back pain (CLBP) patients. The literature on these patients reports that mobility, endurance, trunk strength and lifting capacity decrease during the process of chronicity. Chronically disabled patients appear to have lower functional capacity than asymptomatic persons. METHODS: Our study group consisted of 90 disabled CLBP patients (44 female, 46 male; average age 42 years) who underwent a multidisciplinary 8-week daily treatment program of functional restoration with behavioral support (instruction, endurance training, strength exercises, behavioral and treatment to facilitate return to work therapy). Initially these patients where compared with 107 asymptomatic persons (44 female, 63 male, average age 41 years). The patients were investigated before and after treatment, and at intervals of 6 and 12 months. The reliability of the functional measurements was evaluated by interrater comparison. Physical assessment included a medical examination (mainly diagnosis of radicular or nonradicular pain), changes in the lumbar spine revealed by X-ray studies according to Herron and Turner, rating of physical impairment according to Waddell, flexibility, length of hamstrings muscles (SLR), test of power and endurance of trunk movement by standardized exercises according to the Swiss group of Spring and isokinetic measurements (LIDO Back), tests of lifting capacity (LIDO Lift), and (in part) of general endurance on a cycle ergometer (CASE 15 Marquette). RESULTS: Physical findings showed that mobility was reduced substantially in patients suffering from back pain due to reduced SLR (shortened hamstrings) and decreased spinal mobility. Patients also demonstrated significant reductions in their ability to perform lifting tasks in comparison to healthy individuals. The results of trunk flexion showed no significant differences between patients and the control group, whereas the ability to perform trunk extension was much better in the control group. In principle we found the same results with isokinetic measurements as in the exercises without machines. Cardiovascular endurance was also much better in the control group than it was in the back pain patients. At the end of the treatment program all physical deficits were improved significantly. In many cases performance was comparable with that of the control group. With time, however, training effects gradually decreased. The success of treatment (return to work, absence from work, pain reduction, use of medical care) was independent of the functional status of the patients before and after treatment. CONCLUSION: Study results showed that physical capacity in disabled patients with low back pain is substantially reduced in comparison to persons who do not suffer from back pain. The only exception was in trunk flexor strength and endurance, in which measurements did not differ between the patients and the control group. However, even CLBP- patients with long-term pain and severe physical illness can successfully improve their physical condition by participating in an active treatment program. Back extensor muscle training has to be included in physical therapy. Because of loss of condition during the time after treatment, regular monitoring of patients and their home training programs is necessary. Overall, treatment of CLBP has to include physical training and psychosocial treatment to achieve satisfactory results.

English Abstract↗

M.BssHII, a multispecific cytosine-C5-DNA-methyltransferase with unusual target recognizing properties.

A new multispecific cytosine-C5-DNA-methyltransferase (C5-MTase), M.BssHII, was identified in Bacillus stearothermophilus H3. The M.BssHII gene was cloned and sequenced. The amino acid sequence deduced shows the characteristic building plan of a C5-MTase. By sequencing bisulfite-treated DNA methylated by M.BssHII and by restriction enzyme analysis, we defined the following methylation targets of M.BssHII: ACGCGT/CCGCGG (MluI/SacII), PuGCGCPy (HaeII), PuCCGGPy (Cfr10I) and GCGCGC (BssHII). The relative location of the specificity determinants in the C5-MTase was derived from the analysis of M.BssHII derivatives carrying deletions within the variable region "V" and chimeric C5-Mtases constructed between M.BssHII and the related monospecific enzyme M.phi3TII. Four of the M.BssHII specificities (MluI, SacII, Cfr10I and BssHII) could be associated with amino acid segments within the variable region "V". The determinant for HaeII activity had to be assigned to sequences defining the enzyme core, the first example of a C5-MTase in which a sequence-specific methylation potential is mediated by structures outside of the variable region. Another intriguing result came from the analysis of one particular chimera made between M.BssHII and M.phi3TII. This construct showed a relaxation of the methylation capacity, both with respect to the target recognized and the targeting of methylation within this sequence.

Amino Acid Sequence↗

Spinal metastases of cerebral glioma. Case report.

We report a case of multiple spinal leptomeningeal metastases from an intracerebral glioblastoma and the original tumor having been an oligoastrocytoma (WHO II). Three time resection of this right frontal tumor with opening of the lateral ventricle preceded intraventricular spread. Diagnosis of spinal dissemination was based on the previous history and Gadolineum-DTPA enhanced MR.

Brain Neoplasms↗

Inflammatory reaction and capillary leak syndrome related to cardiopulmonary bypass in neonates undergoing cardiac operations.

We studied the inflammatory reaction related to cardiopulmonary bypass in 24 neonates (median age 6 days) undergoing the arterial switch operation for simple transposition of the great arteries, with respect to the development of postoperative capillary leak syndrome. Complement proteins, leukocyte count, tumor necrosis factor-alpha, and histamine levels were determined before, during, and after cardiopulmonary bypass. Additionally, protein movement from the intravascular into the extravascular space during cardiopulmonary bypass was assessed by the measurement of plasma concentrations of proteins with molecular weights ranging from 21,200 to 718,000. Capillary leak syndrome developed in 13 of the 24 neonates. Patients with capillary leak syndrome, as compared with those without, had preoperatively higher C5a levels (C5a, 3.0 +/- 0.6 microgram/L vs 0.9 +/- 0.2 microgram/L) (mean +/- standard error of the mean) (p < 0.05) and higher leukocyte counts (leukocytes, 17.9 +/- 2.1 X 10(3) cells/ml versus 11.7 +/- 0.8 X 10(3) cells/ml) (p < 0.05), suggesting in these neonates a preoperative inflammatory state. Preoperative clinical and operative data were identical in both patient groups. Before cardiopulmonary bypass, serum protein concentrations were similar in all patients. Ten minutes after institution of cardiopulmonary bypass, protein concentrations fell to significantly lower values in patients with capillary leak syndrome than in those without: albumin (19% +/- 1.5% vs 30% +/- 6% of the prebypass value, p < 0.05), immunoglobulin G (17% +/- 1.5% vs 29% +/- 5.5%, p < 0.001), and alpha 2-macroglobulin (15% +/- 1.2% vs 25% +/- 4%, p < 0.02). During cardiopulmonary bypass, albumin concentrations remained significantly lower in patients with capillary leak syndrome than in those without, whereas hematocrit values were similar in both groups. During cardiopulmonary bypass, patients with capillary leak syndrome also had lower concentrations of complement proteins C3 and C4 but not C1 inhibitor. C3d/C3 ratio and C5a levels were similar in both patient groups. In contrast, histamine liberation during cardiopulmonary bypass was significantly more pronounced in patients with capillary leak syndrome than in those without (725.2 +/- 396.7 pg/ml vs -54.1 +/- 58.4 pg/ml, p < 0.05). Tumor necrosis factor-alpha levels after protamine administration were also significantly higher in patients with capillary leak syndrome (38.1 +/- 10.0 pg/ml vs 15.3 +/- 3.4 pg/ml, p < 0.05). Leukocyte count during and after cardiopulmonary bypass was similar in both patient groups. This study demonstrates increased protein leakage as early as 10 minutes after initiation of.

Acute-Phase Reaction↗

[Transcranial Doppler examination on effect of hemodynamics on cerebral autoregulation in acute cerebral infarct].

AIM: We treated 24 patients suffering from an acute ischemic stroke of the middle cerebral artery, with a hypervolemic hemodilution combined with dopamine/dobutamine. METHOD: The influence of blood pressure and cardiac output on the blood flow velocity in the middle cerebral artery was measured using transcranial Doppler sonography (TCD). RESULTS: Under the hypervolemic hemodilution supported with dopamine/dobutamine a dosage-dependent increase of 12% in blood pressure and a 53% increase in cardiac output was observed. In the affected hemisphere, flow velocity was one fourth lower (significance p < 0.05) than in the unaffected hemisphere. With therapy, the systolic flow velocity was increased in the unaffected hemisphere by 27%, on the side of the lesion only 11%. Mean flow velocity remained nearly constant. The pulsatility index (PI) increased simultaneously by 46% in the affected and 47% in the unaffected hemisphere. CONCLUSION: Similar effects on TCD-flow velocity and PI under comparable slight increases in blood pressure are not known. The increase in cerebrovascular resistance can be ascribed to a counter-regulation of the cerebral autoregulation, triggered by an increase of cardiac output.

Aged↗

Preoperative obesity is associated with decreased survival after heart transplantation.

BACKGROUND: It is difficult to assess candidacy of obese patients for heart transplantation because the effect of obesity before heart transplantation on posttransplantation outcome has not been examined. Therefore, the purpose of this study was to examine the impact of both preoperative weight and postoperative weight gain on outcome after heart transplantation. METHODS: The retrospective sample included 193 consecutive patients undergoing transplantation between March 1984 and June 1991 (mean age 47 +/- 14 years, 75% male). Data were gathered from retrospective chart review. Percent ideal body weight was calculated for each patient. Patients were divided into three groups based on pretransplantation percent ideal body weight: < 90% ideal body weight (n = 30), 90% to 110% ideal body weight (n = 79), and > 110% ideal body weight (n = 84). Chi-square, analysis of variance, Kaplan-Meier survival distributions, and the Cox Proportional Hazards Model were used for analyses. RESULTS: Patients > 110% ideal body weight tended to have more coronary artery disease and higher serum triglyceride levels and significantly higher cholesterol levels than patients < 90% ideal body weight. After heart transplantation, no significant differences were found among the three pretransplantation percent ideal body weight groups regarding acute rejection, infection, and allograft arteriopathy. Survival was significantly worse among patients who were overweight before surgery (p = 0.018). A multivariate survival analysis showed that percent ideal body weight was an independent predictor of survival after heart transplantation (p = 0.046). CONCLUSIONS: Despite a similar incidence of infection and rejection after heart transplantation among the three percent ideal body weight groups, obesity before heart transplantation is associated with significantly decreased survival after heart transplantation.

Adolescent↗

[Interrater studies of evaluating the reliability of somatic findings].

20 patients (11 female, 9 male) without low back pain were included in two interrater studies carried out by three physical therapists. The following variables were investigated: shape of the spine, iliac crest heights, twisting of the pelvis, spine test, length of legs, Patrick sign, Schober test, fingertip-to-floor measurements, flexion and extension of the lumbar spine, straight-leg raising, and length of the iliopsoas and the rectus muscles. Intraclass coefficients for the ordinal variables, and kappa coefficients for the nominal variables were calculated for evaluation of interrater agreement. In both investigations, the Schober sign, lumbar flexion, fingertip-to-floor measurements, straight-leg raising of the left leg, and lengths of both legs were almost perfectly reliable. All other variables exhibited a lower reliability between the three therapists.

Adult↗

Magnetic resonance imaging in spinal emergency.

We studied the diagnostic value of MRI in spinal emergency. One hundred patients were analyzed retrospectively and the MR-findings were compared with operative results or autopsy whenever available. The advantages of MRI compared to CT and conventional myelography are discussed. The limitations of MRI are addressed and the important features of appropriate diagnostic procedure are outlined with special attention to neurosurgical requirements.

Adolescent↗