Biomedical subjects

K C Koch

Publications and source records attributed to K C Koch.

24 records · Page 2Linked to original sources

PubMed1996

Imaging of beta-oxidation by static PET with 14(R,S)-[18F]-fluoro-6-thiaheptadecanoic acid (FTHA) in patients with advanced coronary heart disease: a comparison with 18FDG-PET and 99Tcm-MIBI SPET.

14(R,S)-[18F]-fluoro-6-thiaheptadecanoic acid (FTHA) has been proposed as a PET tracer of the beta-oxidation pathway. The aim of this study was to investigate the diagnostic value of FTHA using static PET imaging in patients with ischaemically reduced left ventricular function. Twenty-one patients with angiographically proven advanced coronary heart disease were examined. All patients underwent SPET with 400 MBq [99Tcm]-2-methoxy-isobutyl-isonitrile (MIBI) for perfusion assessment and PET with 250 MBq FTHA under fasting conditions and with 150 MBq 2-[18F]-fluoro-2-deoxyglucose (FDG) following an oral glucose load. The uptake of FTHA and FDG was analysed quantitatively in 33 regions. Regional uptake was normalized to the region with highest MIBI uptake and expressed as a percentage. FTHA uptake paralleled MIBI uptake (r = 0.80) but not FDG uptake (r = 0.57). Mean FTHA uptake (38.1 +/- 16.3%) in 190 regions with severely reduced perfusion (MIBI uptake < 50%, mean uptake 36.8 +/- 9.4%) was significantly lower compared to FDG uptake (54.6 +/- 25.0%). FTHA uptake was preserved (> or = 70%) in 8 of 52 (13%) regions only with severely reduced perfusion but preserved glucose metabolism (FDG uptake > or = 70%). The similarity between FTHA and MIBI uptake suggests that static PET imaging with FTHA is of limited value when distinguishing between ischaemic or hibernating myocardium and scar. The underestimation of viability may be caused both by the dependence of uptake on flow and the suppression of beta-oxidation in regional chronic ischaemia under fasting conditions.

Aged↗

PubMed1996

[Assessment of myocardial viability using 201TL SPECT at rest to predict the reversibility of left ventricular wall motion abnormalities].

AIM: The aim of the present study was to predict preoperatively the reversibility of left ventricular wall motion abnormalities using TI-201 SPECT at rest. METHODS: 19 patients with advanced coronary artery disease and regional wall motion abnormalities were examined at rest with TI 201 SPECT (acquisition 15 minutes and 3 hours post injection). Successfully revascularized, proven by a second coronary angiography three month after revascularisation. Wall motion was again evaluated by cineventriculography. RESULTS: The preoperative a- or dyskinetic segments were best separated by the minimal relative TI-201 uptake in the defect 3 hrs p.i. in (i) postinterventionally improved wall motion (TI-201 uptake 67 +/- 14%, viable) and in (ii) without recovery (TI-201 uptake 46 +/- 12%, p < 0.001, non viable). A threshold at a TI-201 uptake of more than 50% yielded a positive predictive value of 0.73 and a negative predictive value of 0.86. If the segments with wall motion abnormalities (hypokinetic included) were evaluated as one group, no such threshold was obtained all segments which occurred a TI-201 uptake of more than 80% showed a functional recovery, wall motion did not improve in any segment with a TI-201 uptake of less than 40%. In the present study a considerable influence of the defect localisation with regard to the posterior wall was not observed. The values of TI-201 redistribution under resting condition were not useful to predict functional recovery. CONCLUSION: TI-201 SPECT in rest predicts preoperatively the reversibility in regions with severe wall motion abnormalities only and indicates myocardial viability in these cases. Thus, the method is basically useful to determine myocardial viability. In hypokinetic segments, however, a wide range of TL-201 uptake values exists without definite evidence to functional recovery.

Aged↗

PubMed1996

[Effect of myocardial viability and coronary revascularization on clinical outcome and prognosis: a follow-up study of 161 patients with coronary heart disease].

One hundred and sixty-one consecutive patients (144 male, 57 +/- 9 years) with stable coronary artery disease underwent nuclear imaging for assessment of myocardial viability using Tc-99m sestamibi single-photon emission computed tomography (SPECT) and F-18 fluoro-deoxy-glucose (FDG) positron emission tomography (PET). 88% had a history of chronic myocardial infarction and all had angiographically proven regional wall motion (RWM) abnormalities in the distribution territory of a stenosed or occluded coronary artery. Patients were followed for 29 +/- 6 (22-44) months with 84/161 patients (52%) receiving elective revascularization by either bypass surgery or angioplasty. 61/84 patients underwent follow-up angiography after 5 +/- 2 months for quantitative assessment of RWM changes using serial analysis with the centerline method in 45 pts with technically suitable paired angiograms. Myocardial regions were classified according to semiquantitative analysis of regional sestamibi and FDG uptake as either normal, regions with evidence for maintained viability but no mismatch ("mild match"), regions with a perfusion/metabolism "mismatch," or scar. RWM improved in "mismatch" regions from -2.2 +/- 1.0 SD to -1.0 +/- 1.4 SD (p < 0.01) compared to the mean of a normal reference population. In contrast, in regions with a "mild match" or those classified as scar, RWM analysis revealed no functional changes at follow-up. For the assessment of clinical outcome, patients were divided into three groups depending on the result of viability imaging. Those with predominantly scar tissue in the target region for viability assessment (group A, n = 90), those with a "mild match" (B, n = 26), and group C (n = 45) consisting of patients with a "mismatch" pattern. Subsequent treatment was not blinded to nuclear imaging results and revascularization was performed in 30% of group A (group A2), 81% of group B, and 80% of group C, while the other patients were treated medically only. Cardiac events during follow-up were defined as cardiac death, myocardial infarction, unstable angina with subsequent revascularization, cardiac transplantation, and survived resuscitation without evidence for myocardial infarction. Group C demonstrated a significant reduction of cardiac events from 22% to 0% following revascularization, whereas in group A coronary revascularization did not influence the frequency of events. Subjective assessment of angina pectoris and heart failure symptoms revealed more patients with improvement following revascularization as compared to those treated medically. Thus, combined nuclear imaging using sestamibi SPECT and FDG PET with quantitative tracer uptake analysis allows detection of absent or preserved myocardial viability in regions with reduced perfusion and function with prognostic implication for regional myocardial functional outcome as well as for identification of patients who benefit most from coronary revascularization.

Adult↗

PubMed1992

Interleukin 4 (IL) 4 up-regulates gene and surface IL 1 receptor type I in murine T helper type 2 cells.

The T cell-derived cytokine interleukin (IL) 4 is known to increase the proliferative response of T cells stimulated with IL 1. IL 4 is also an autocrine growth factor for type II T helper cells (Th2) cells. In the present studies, we examined the effect of murine recombinant IL 4 on the expression of the IL 1 receptor type I (IL 1RtI) in murine Th2 cell lines at the mRNA and surface level. Using a specific anti-murine IL 1RtI monoclonal antibody and flow microfluorometry, we found that IL 4 increased the surface expression of IL 1RtI in a dose-dependent manner. In D10S cells, a subline of the Th2 cell line D10.G4.1, 50-500 pg/ml IL 4 up-regulated the receptor 1.8- to 3.2-fold (p less than 0.05). This up-regulation was also seen at the mRNA level. The effect was not due to increased stability of the mRNA, since IL 4 did not modify the half-life of IL 1RtI mRNA. IL 4 also up-regulated IL 1RtI on CDC25 cells, another Th2 cell line. However, we did not observe an effect of IL 4 on gene expression of IL 1RtI in BALB/c 3T3 fibroblasts. IL 2 and IL 4 showed an additive effect in up-regulating IL 1RtI and D10S cells. These studies indicate that IL 4 up-regulates IL 1RtI in murine Th2 cells by increasing gene expression for IL 1RtI without affecting mRNA stability. Thus, IL 4 production by Th2 cells may amplify the immune response via up-regulation of IL 1RtI.

Animals↗

PubMed1992

Interleukin-1 down-regulates gene and surface expression of interleukin-1 receptor type I by destabilizing its mRNA whereas interleukin-2 increases its expression.

The interleukin-1 receptor type I (IL-1RtI) plays an important role in the biological effects of IL-1, but regulation of its surface and gene expression remains unknown. We found that occupancy of 2-15% of the IL-1 surface receptor results in dramatic down-regulation of IL-1RtI both at the mRNA and cell surface level in murine D10S cells, a subline of T-helper type 2 cells. At these low occupancy levels (3 x 10(-12) to 3 x 10(-13) M), the reduction in IL-1RtI surface expression appears at 24 hr and continues to 48 and 72 hr. At the mRNA level, low occupancy of the IL-1R results in decreased IL-1RtI mRNA stability; steady state half-life of the IL-1RtI mRNA is reduced from 6 to 1 hr after exposure to 3 x 10(-12) M IL-1. This down-regulation of IL-1RtI by IL-1 is blocked by cycloheximide, suggesting de novo protein synthesis is necessary for decreased RNA stability. Low concentrations of human IL-1 beta, murine and rabbit IL-1 alpha or beta similarly down-regulated IL-1RtI, whereas low concentrations of human IL-1 alpha failed to reduce the receptor surface expression, despite inducing a full proliferative response. We also observed that the effect of IL-1 on this down-regulation was not through protein kinase C (PKC), since PMA rapidly increased IL-1RtI mRNA levels within 30 min and persisted for 24 hr. IL-2 up-regulated IL-1RtI in D10S cells at both mRNA and protein levels. These results demonstrate that low occupancy of IL-1 receptors induces down-regulation of IL-1RtI surface as well as mRNA expression. The regulation of IL-1RtI gene expression may be one of the mechanisms by which IL-1-mediated events are controlled.

Animals↗

PubMed1991

The role of C5a in interleukin-6 production induced by lipopolysaccharide or interleukin-1.

We investigated the effects of recombinant C5a on interleukin-6 (IL-6) production by peripheral blood mononuclear cells (PBMC) in vitro and compared them with the release of interleukin-1 (IL-1) and tumour necrosis factor (TNF). In a virtually lipopolysaccharide (LPS)-free culture system, C5a by itself did not induce any significant IL-6 translation. The IL-6 release in response to low amounts of LPS (500 pg/ml) or IL-1 beta, however, was markedly increased by the complement fragment. This enhancement of IL-6 synthesis was dose-dependent, reached its optimum at 5.8 x 10(-9)M rC5a and occurred regardless of the presence of serum components. At the level of transcription C5a by itself did not induce IL-6 gene expression, but in the presence of low amounts of LPS the stimulation of monocytes with C5a yielded an increase in IL-6 mRNA. The transcription of IL-1 beta, however, can be induced by C5a alone. These data are interesting, since they indicate a different regulation of IL-1 beta and IL-6 by the complement fragment C5a. Furthermore, we could show that the C5a-mediated IL-6 production influenced the synthesis of IgG rather than IgM in vitro. These results may be relevant for an understanding of the potentiating role of C5a in cytokine-dependent disease processes.

Cells, Cultured↗