Biomedical subjects
Publications and source records attributed to M Koch.
Explore the source record for details and available documents.
A retrospective multicentre survey was conducted to evaluate, in patients with chronic hepatitis C, the long-term liver histological changes induced by interferon (IFN). A total of 112 patients (mean age 46.4 years) were studied. All patients had received a 6-12-month IFN-alpha course (6-18 MU/week) and had successively undergone clinical, biochemical and virological follow-up for at least 36 months (range: 36-76). In each patient, two liver biopsies had been performed: 1-6 months before treatment and, 12-76 months after its completion. In 87 patients with biochemical and virological sustained response persisting for 12 months after therapy, post-treatment liver necroinflammation and fibrosis mean(+/-SD) scores (Knodell index) were significantly lower than pretreatment scores (2.9 +/- 2.2 vs 6.8 +/- 2.9 and 0.8 +/- 1.0 vs 1.2 +/- 1.1, respectively; P < 0.01). In 25 patients who relapsed within 1 year, necroinflammation and fibrosis post-treatment mean scores were similar to pretreatment scores (7.4 +/- 3.2 vs 6.9 +/- 3.1 and 1.8 +/- 1.3 vs 1.6 +/- 1.2, respectively; P > 0.05). On an individual basis, necroinflammation decreased in 87% of sustained responders but only in 36% of relapsers (P < 0.001), whereas fibrosis decreased in 44% of sustained responders but only in 14% of relapsers (P < 0.001). In sustained responders with biopsies performed 12-23 months (n=34), 24-35 months (n=26) or more than 36 months (n=27) after treatment, a progressive decrease of mean necroinflammatory score was observed (-2.6 +/- 2.1, -4.1 +/- 3.4 and -5.2 +/- 3.7 points, respectively; P < 0.01). A similar pattern was observed in fibrosis score (-0.3 +/- 0.6, -0.3 +/- 0.7 and -0.7 +/- 0.9 points, respectively; P < 0.05). Hence, among chronic hepatitis C patients treated with IFN, those with a 12-month sustained response, unlike those who relapse, have a long-term progressive reduction and, in some cases, a complete regression of liver histological damage.
BACKGROUND: The aim of this study was to determine the incidence and role of CD117 (c-KIT) overexpression as a predictive/prognostic marker in extensive-stage small-cell lung carcinoma (ESSCLC). We performed a retrospective study on subjects with a biopsy-proven diagnosis of ESSCLC. PATIENTS AND METHODS: A chart review for demographic and clinical data was performed on patients with ESSCLC diagnosed between 1991 and 2001. CD117 overexpression was evaluated using immunohistochemistry (A4052 polyclonal antibody) performed on archival paraffin-embedded specimens. RESULTS: Two hundred and twenty-three patients with ESSCLC were identified, of whom 193 (84 females, 109 males) with a mean age of 68.5 years (range 42-90) had adequate tissue specimens available for CD117 testing. The most commonly presenting symptom was weight loss, seen in 61 patients (31.6%). Of the 193 specimens, 54 (27.9%) showed CD117 overexpression. The median length of survival for CD117-positive patients was 9 months as compared with the CD117-negative population, in whom the survival was 6 months (P = 0.025, Cox proportional hazard method). CONCLUSIONS: CD117 overexpression detected using immunohistochemistry is observed in about a third of patients with ESSCLC and does not have statistically significant prognostic value. However, CD117 may be a potential target for site-specific immunotherapy in ESSCLC. Our findings suggest a role for clinical trials assessing the role of selective tyrosine kinase inhibitor STI-571 (alone or in combination with conventional therapy) in patients with ESSCLC.
BACKGROUND: Of patients with superficial bladder cancer, a group are still at risk of disease recurrence, progression and death from their cancer after curative treatment. Angiogenesis is a crucial pathogenic mechanism for this type of urothelial cell carcinoma (UCC), and is a potential therapeutic target. However, the selection of the appropriate patients remains a dilemma. PATIENTS AND METHODS: Vascular endothelial growth factor (VEGF) expression and the presence of angiogenesis and occurrence of CD31, CD34, endoglin and factor VIII immunoexpression, were evaluated in 66 superficial papillary UCCs of the bladder and were correlated with classical histopathological factors and disease outcome. RESULTS: VEGF immunoreactivity was observed in 100% of cases, and more intensely in the luminal surface. The presence of microvessel clusters independently of a fibrovascular core was observed in 22.7% of cases. Of these, the T1/G2 subgroup had an independent and significantly lower recurrence-free survival (P = 0.0002). CONCLUSIONS: These results indicate that the presence of angiogenesis in tumour urothelium is a potential prognostic factor in superficial UCC, particularly in T1/G2 tumours, and may be used to select patients for anti-angiogenic treatments.
Epidemiological studies have shown increased incidence of schizophrenia in patients subjected to different forms of pre- or perinatal stress. However, as the onset of schizophrenic illness does not usually occur until adolescence or early adulthood, it is not yet fully understood how disruption of early brain development may ultimately lead to malfunction years later. In order to elucidate a possible role for neurodevelopmental factors in the pathogenesis of schizophrenia and to highlight potential new treatments, animal models are needed. Prepulse inhibition (PPI) is a model of sensorimotor gating mechanisms in the brain. It is disrupted in schizophrenia patients and the disruption can be reversed with atypical antipsychotics. It has been widely used in animal studies to explore central mechanisms possibly involved in schizophrenia. There has been a recent surge of behavioural and neurochemical animal studies on neurodevelopmental models, particularly on the effects of postweaning isolation, maternal separation and neonatal lesions of the hippocampus. In these models, long lasting alterations in behaviour and/or molecular changes in specific brain regions are observed, comparable to those seen in schizophrenia. The aim of this article is to critically review the available literature on such neurodevelopmental animal models with special focus on the effects on PPI and brain regions that are putatively involved in regulation of PPI.
We present a THz investigation of histo-pathological samples including the larynx of a pig and a human liver with metastasis. Our measurements show that different types of tissue can be clearly distinguished in THz transmission images, either within a single image or by a comparison of images obtained for different frequency windows. This leads to the problem that images obtained for different frequencies inherently have a different spatial resolution. An image obtained from two such images by a simple mathematical operation may contain artefacts. We discuss measures to deal with this problem. Furthermore, we investigate the possibility of improving the spatial resolution of THz images. Finally, we present a cw THz imaging system based on a photomixer and an external cavity semiconductor laser that allows for simultaneous two-mode operation. The cw system is less expensive and more compact than conventional time-domain imaging systems.
The rat pineal organ is an established model to study signal transduction cascades that are activated by norepinephrine (NE) and cause increases in cAMP levels and stimulation of protein kinase A (PKA). PKA type II catalyzes the phosphorylation of the transcription factor cAMP-response-element-binding protein (CREB) which is essential for the transcriptional induction of the arylalkylamine- N-acetyltransferase (AANAT), the rate limiting enzyme of melatonin biosynthesis. Moreover, PKA may control protein levels and enzyme activity via two PKA-dependent phosphorylation sites in the AANAT molecule. Despite the functional importance of PKA very little is known about the distribution of its isoenzymes and of A-kinase anchor proteins (AKAPs) that target the PKA to specific membrane areas and organelles by binding to the regulatory (R) subunits of PKA. We have addressed this problem by demonstrating the R subunits alpha and beta of PKA type I and II and two AKAPs (150 and 95) in NE-stimulated and untreated rat pinealocytes by immunoblot and immunocytochemistry. The immunoreactions (IR) of all four R subunits were confined to granules evenly distributed in the pinealocyte cytoplasm. Immunoreactions of RIIalpha and RIIbeta were stronger than those of RIalpha and RIbeta. AKAP 150-IR was concentrated at the cell periphery; AKAP 95-IR was restricted to the nucleus. Amount and subcellular distribution of the immunoreactions of all proteins investigated did not change upon NE stimulation. A substantial colocalization was observed between RII-subunits and AKAP 150-IR, suggesting that, in rat pinealocytes, AKAP 150 primarily anchors the R subunits of PKA II.
Esthesioneuroblastoma is a rare tumor, which in many cases is diagnosed at an advanced stage with an high recurrence rate and incidence of metastases. Regionary metastases predict a poor prognosis. There is no standard therapy approach for these tumors. The most widly accepted primary therapy is radical craniofacial enbloc resection followed by radiation therapy. Today chemotherapy is getting more important and is administered with curative intention. Multidisciplinary management results in significantly longer survival in advanced tumor stages and recurrence. A clinical staging system as well as histopathological grading according of Hyams could be from importance for selection and timing of the different therapeutic modalities. We present a case of a 34-year-old female patient who was diagnosed with an advanced olfactory neuroblastoma of the upper nasal cavity with bilateral cervical lymph node metastasis (modified Kadish-stage D). Craniofacial resection and bilateral neck dissection was performed, followed by postoperative radiotherapy. Reviewing the recent literature the different therapeutic approaches are compared and discussed.
The fear-potentiated startle paradigm (i.e., the enhancement of the startle response in the presence of an aversive conditioned stimulus) is a valuable cross-species model for the study of the neuronal mechanisms underlying fear and anxiety as well as of the cognitive control of those aversive states. Walker et al. present data from a study in rats indicating that extinction of fear in the fear-potentiated startle paradigm is enhanced by the partial agonist of the N-methyl-D-aspartate receptor D-cycloserine (DCS). The authors therefore suggest tests of DCS in clinical trials as a potential pharmacotherapeutic adjuvant for exposition therapies in fear and anxiety disorders.
Conflicting data on the inotropic effect of insulin are present in the literature suggesting a positive inotropic property or no inotropic effect or even a negative influence. To clarify the reason for these diverging findings, dose-response curves of insulin have been performed in isolated working rat and guinea pig hearts perfused with Krebs-Henseleit buffer containing 0.9, 1.25, 2.5, and 5 mM Ca(2+) at 37 degrees C. At 1.25 mM [Ca(2+)], insulin (8 to 16 IU) regularly improved the inotropic state. LVdP/dt(max) increased significantly from 1,900 to 2,300 mm Hg/s (+21 %) in guinea pig hearts and from 3,197 to 4,345 mm Hg/s (+36 %) in rat hearts. LVEDP did not change significantly. Myocardial oxygen consumption increased parallel with contractility. Heart rate was not influenced in either species. Coronary flow increased by 16.5 % in guinea pig hearts, but decreased in rat hearts by 13.6 % (p < 0.05 each). With 0.9 mM [Ca(2+)] the positive inotropic effect of insulin did not further augment. At 2.5 mM [Ca(2+)] insulin exhibited in both species no significant change of LVdP/dt(max) but very high insulin doses depressed the heart. At 5 mM [Ca(2+)] insulin depressed the heart significantly already at lower concentrations. At 31 degrees C and 1.25 mM [Ca(2+)] the positive inotropic insulin effect was preserved. We conclude that the positive inotropic insulin effect in rat and guinea pig hearts depends on the extracellular [Ca(2+)], i.e., is maximal around 1.25 mM [Ca(2+)] and is reduced or absent at higher [Ca(2+)] or may even become negative.
Phytochemical studies on the stem bark of Guibourtia tessmanii yielded a dihydrochalcone glucoside, 2',4-dihydroxy-4'-methoxy-6'-O-beta-glucopyranoside dihydrochalcone and a new stilbene glycoside, 3,5-dimethoxy-4'-O-(beta-rhamnopyranosyl-(1-->6)-beta- glucopyranoside) stilbene besides the known pterostilbene. Their structures were established on the basis of one and two dimensional NMR spectroscopic techniques, FABMS and chemical evidence.
The combination of chemical and biological water treatment processes is a promising technique to reduce recalcitrant wastewater loads. The key to the efficiency of such a system is a better understanding of the mechanisms involved during the degradation processes. Ozonation has been applied to many fields in water and wastewater treatment. Especially for textile mill effluents ozonation can achieve high color removal, enhance biodegradability, destroy phenols and reduce the chemical oxygen demand (COD). However, little is known about the reaction intermediates and products formed during ozonation. This work deals with the degradation of hydrolyzed Reactive Yellow 84 (Color Index), a widely used azo dye in textile finishing processes with two monochlorotriazine anchor groups. Ozonation of the hydrolyzed dye in ultra pure water was performed in a laboratory scale cylindric batch reactor. Decolorization, determined by measuring the light absorbance at the maximum wavelength in the visible range (400 nm), was almost complete after 60 and 90 min with an ozone concentration of 18.5 and 9.1 mg/l, respectively. The TOC/TOC0 ratio after ozonation was about 30%, the COD was diminished to 50% of the initial value. The BOD5/COD ratio increased from 0.01 to about 0.8. Oxidation and cleavage of the azo group yield nitrate. Cleavage of the sulfonic acid groups of aromatic rings caused increases in the amount of sulfate. Formic acid and oxalic acid were identified as main oxidation products by high performance ion chromatography (HPIC). The concentrations of these major products were monitored at defined time intervals during ozonation.
PURPOSE: To investigate the potential of fMRI to measure changes in fetal tissue oxygenation during acute maternal hypoxia in fetal lambs. MATERIAL AND METHODS: Two ewes carrying singleton fetuses (gestational age 125 and 131 days) underwent MR imaging under inhalation anesthesia. BOLD imaging of the fetal brain, liver and myocardium was performed during acute maternal hypoxia (oxygen replaced by N 2 O). Maternal oxygen saturation and heart rate were monitored by a pulse-oxymeter attached to the maternal tongue. RESULTS: Changes of fetal tissue oxygenation during maternal hypoxia were clearly visible with BOLD MRI. Signal intensity decreases were more distinct in liver and heart ( approximately 40 %) from control than in the fetal brain ( approximately 10 %). CONCLUSIONS: fMRI is a promising diagnostic tool to determine fetal tissue oxygenation and may open new opportunities in monitoring fetal well being in high risk pregnancies complicated by uteroplacentar insufficiency. Different signal changes in liver/heart and brain may reflect a centralization of the fetal blood flow.
Cannabinoids can disrupt short-term memory in humans and animals and induce learning deficits and other cognitive impairments. In the present study we examined the role of a full cannabinoid agonist in short-term memory, sensorimotor gating, and the acquisition and expression of an operant learning paradigm in rats. We tested the effects of the synthetic cannabinoid WIN 55,212-2 (0.6 and 1.2 mg/kg) on short-term memory in social and object recognition tests, on prepulse inhibition (PPI) of startle, as well as on lever pressing for palatable food. Injections of 0.6 and 1.2 mg/kg WIN 55,212-2 impaired recognition memory and PPI in a dose-dependent manner, but had no effect on lever-pressing acquisition or expression, or on food preference. The PPI deficit was reversed by the administration of 0.1 mg/kg haloperidol. These data suggest that the synthetic cannabinoid WIN 55,212-2 does not lead to a general impairment of learning in an appetitive instrumental task, but significantly affects short-term memory and sensorimotor integration. The impairment in recognition and PPI might be due to deficits in attention-based short-term information processing.
Explore the source record for details and available documents.
Chick cDNA clones for a new member of the FACIT (fibril-associated collagens with interrupted triple helices) subfamily have been isolated and sequenced. The collagen chain encoded by these cDNAs was assigned the next consecutive number, making it the alpha1(XX) collagen chain. Assignment of type XX collagen to the FACIT family was based on sequence similarities to types XII and XIV collagen. Type XX collagen mRNA is not abundant in the chick embryo. It is most prevalent in corneal epithelium. It is also detectable by reverse transcription polymerase chain reaction in embryonic skin, sternal cartilage, and tendon, but is barely detectable in calvaria, notochord, or neural retina at select stages of development, suggesting that it is not expressed in these tissues. The cDNA predicts that the alpha1(XX) collagen polypeptide is smaller than the short forms of collagen XII and XIV. A polyclonal antibody against a synthetic alpha1(XX) peptide reacts with polypeptide bands of 185, 170, and 135 kDa by Western blot analysis. From its similarity to types XII and XIV collagen, type XX is expected to bind to collagen fibrils, projecting the amino-terminal domains away from the fibrillar surface. The projecting NC 3 domains are predicted to be about half the length of those of collagen XIV.
Signal transducer and transcriptional activator (STAT) proteins are latent cytoplasmic transcription factors that are activated in response to stimulation by various cytokines. Protein Inhibitors of Activated STAT (PIAS) proteins comprise a family of five mammalian proteins which have been identified as potentially important downregulators of the STAT signaling pathway. We have previously reported the identification and expression of the mouse homologue of PIAS family member PIASgamma. Here we report the isolation by genomic 5'-RACE PCR and in vitro analysis of the mouse PIASgamma promoter region and the genomic structure and organization of the mouse and human PIASgamma genes. Human PIASgamma spans approximately 23 kb on chromosome 19 and is organized into ten exons. The size of mouse PIASgamma is 16 kb and also organized into ten exons with the intron/exon structure of the two genes conserved in both species. As a result, considerable conservatism of the mouse and human intron sequences was observed. Analysis of a 1.4 kb genomic fragment containing the mouse PIASgamma promoter allowed us to map the transcription 'Start' site of the gene, determine the sequences essential for the activity of this promoter and to define a minimal promoter region.
Explore the source record for details and available documents.