APMIS. Supplementum最新文献

Tissue factor pathway inhibitor (TFPI) acts by complexing with tissue factor and factors VIIa and Xa to retard the extrinsic pathway of the coagulative process. The present study was designed to assess the antithrombotic properties of topically applied TFPI in a model of rabbit arterial thrombosis. A standardised, thrombogenic end-to-end anastomosis was made on the central ear artery. The anastomotic site was irrigated with vehicle (control, n = 5), TFPI 4 micrograms/ml (n = 8), TFPI 40 micrograms/ml (n = 8), or heparin 100 IE/ml (n = 7). The growing thrombus was observed under a stereo microscope. The image was displayed on a video monitor and recorded for analysis using computer assisted planimetry. Topical application of TFPI in either concentration or heparin did not change maximal thrombus size, mean thrombus size, or time to maximal thrombus size significantly when compared to the contralateral vehicle-treated ear. Significant anastomotic bleeding was observed in vessels treated with TFPI 40 micrograms/ml (p < 0.05).

Carcinoma in situ of the breast (CIS) comprise a heterogenous group of lesions, covering a wide spectrum of clinical conditions and histopathological changes. With respect to biological behavior, CIS range from biologically aggressive lesions with a substantial risk of progression into invasive carcinoma (IC), to lesions with a very low malignant potential. Two main types of CIS are described--ductal carcinoma in situ (DCIS) and lobular carcinoma in situ (LCIS). Previous studies of CIS indicate that approximately a third will subsequently develop IC. Autopsy studies indicate that CIS is frequently occurring and it was estimated that about 20% of all women will develop CIS during lifetime. Only a minor fraction is ever diagnosed, although the incidence of DCIS is increasing, especially related to mammography screening. The lack of knowledge about the biological significance of the histopathological subtypes was the background of the present study. In 1982, a nationwide, prospective study of CIS (protocol DBCG 82-IS) was initiated by the Danish Breast Cancer Cooperative Group (DBCG). From this protocol, the group of patients treated with breast conservation surgery (BCS) constituted the material for clinico-histological investigation. A total of 275 women were included in the period 1982-89. Follow-up studies showed that recurrence rate was significantly related to nuclear size of the primary lesion. Since nuclear changes might be related to DNA content and, furthermore, many invasive breast carcinomas were shown to be DNA aneuploid, flow cytometric (FCM) DNA ploidy analysis was performed in a series of DCIS lesions. More than 80% of these lesions were DNA aneuploid, with a distribution similar to that found in invasive carcinomas. This finding raised the hypothesis that the DNA pattern of an invasive carcinoma was already established at the preinvasive stage of DCIS. Therefore, FCM DNA analysis was performed on a series of ICs with predominance of DCIS. Partial or complete concordance in DNA ploidy between DCIS and IC within the individual case was found in most cases, except for the additional presence in the IC component of DNA hyperdiploid clones that might possibly be of importance for the process of invasion. In order to further characterize CIS lesions and, possibly, to discriminate biologically different groups, immunohistochemical markers were investigated in a consecutive series of CIS and IC with predominance of DCIS. The results were correlated to the histopathological and DNA ploidy findings. In DCIS, significant correlation was shown between large nuclear size and comedonecrosis, both of which showed also strong association to DNA aneuploidy, high proliferation activity, low steroid receptor content, and overexpression of c-erbB-2 and p53--factors that may indicate an aggressive behavior. Small nuclear CIS, whether LCIS or DCIS, on the contrary, were DNA diploid with low proliferation, and no cases showed overexpression of c-erb

Protein folding and quality control in the endoplasmic reticulum (ER) are synchronized mechanisms ensuring that only properly folded proteins are integrated in the plasma membrane or secreted from the cell. These mechanisms act in close collaboration with the molecular machinery involved in retrograde-translocation and degradation of non-native proteins and with the ER-stress activated signalling systems. The common goal of these mechanisms is to prevent expression and secretion of misfolded proteins. Protein misfolding can be detrimental to the cell and contributes to the disease mechanism in several inherited disorders, e.g. cystic fibrosis, familial hypercholesterolemia and diabetes insipidus. This review outlines the molecular mechanisms in protein quality control occurring in the ER, signalling caused by ER stress, and finally ER associated protein degradation.

To assess the feasibility of a new variant of laparoscopic Cohen cross-trigonal ureter reimplantation in vesico-ureteral reflux (VUR) using telesurgical equipment. VUR was induced in 8 female pigs by transurethral unroofing of the ureteric orifices. Three months later the reflux was verified by a cystography. A cross-trigonal ureter reimplantation a.m. Cohen was performed by laparoscopic access to the bladder using the da Vinci telesurgical system. The 12 mm camera port was placed below the umbilicus, two 8 mm working ports for the robotic system were placed lateral to the rectus muscles and an additional port for assistance between camera and right working port. The outcome was assessed 3 months later by a new cystography. The operative time for a single reimplantation varied from 45 to 90 minutes. In all pigs the reflux disappeared after the procedure, which was complicated by a postoperative port hernia in two animals. Laparoscopic transvesical ureter reimplantation using telesurgical equipment is a feasible method in the few cases this procedure is indicated. The advantage of the robotic equipment is the better access to submucosal tunneling of the ureter and the intravesical suturing of the anastomosis indicated by shorter operative time and success rates similar to the open procedure.

Only some twenty years has passed since the first discovery of severe immunodeficiency among previously healthy homosexual men through the discovery of the causing virus and till the status today where the knowledge on the HIV virus and the pathogenic mechanisms induced by the virus are extensive, though still incomplete. Furthermore, steadily better treatments have been introduced at a paste that is probably without precedents. These processes have been fuelled by various molecular biological methods. The abilities to quantify viremia and to sequence virus and hence describe the evolution of the virus represent valuable tools for understanding the pathogenic processes. The current thesis describes some of the findings obtained. While it was initially thought that the virological profile mimicked the clinical with an acute infection followed for years by clinical latency and only after on average ten years signs of severe immunodeficiency, this understanding has been revised. There is no virological latency. The viral replication is on going throughout the infection. However, the virological profile does resemble the clinical. Viremia is high shortly after infection; hereafter declines, and stabilises around what has been termed the viral set point. This level of viremia is predictive of the clinical course of the infection. We have shown that the viremic levels, measured both as HIV RNA load and proviral DNA load, early in infection carry significant information about the course of the infection. It is; however, not only early viral loads that carry prognostic information, also viral load during late-stage infection is clinically informative. Viral load measurements have evolved as the major tool for monitoring the efficacy of antiretroviral therapy. HIV RNA has been shown to be a good surrogate marker for the clinical efficacy of antiretroviral treatment. How to use the measurements most optimally has however not been fully delineated. Various methods for describing virological response might yield different results, and it is recommended that the pros and cons of the various methods be investigated. In a cohort of patients who had obtained good virological suppression on antiretroviral therapy followed prospectively for two years we found that only few patients experienced high-grade viremia. Furthermore, baseline HIV DNA differed between the patients with various longitudinal HIV RNA profiles. The patients with the most pronounced HIV RNA suppression had lowest proviral load at baseline, with a clear gradient across the groups. The interplay between proviral load and treatment response deserves further investigations. Resistance can develop against all the available antiretrovirals. The high turnover rate of HIV along with the error-prone reverse transcriptase leads to the possibility of steady accumulation of resistance mutations if the viremic suppression is incomplete. While the interplay between viremia and resistance development is

Blood-brain transfer of oxygen is a fundamental function of regional oxygen consumption. This function yielded a novel description of the mechanism of flow-metabolism coupling. The description revealed that constant oxygen consumption is not maintained by saturation of cytochrome oxidase but by adjustment of the enzyme's affinity towards oxygen. Interactions of oxygen and a factor that could be nitric oxide, at both cytochrome oxidase and nitric oxide synthase, match the affinities of both enzymes towards their respective substrates to the oxygen requirement of the tissue and, in doing so, explain several properties of flow-metabolism coupling.

When surveying the classical biomechanical theory of flow and resistance, the passive elastic properties of the urethra seems to be important for the transport of urine though the urethra. The aim of this study was to show that scanning acoustic microscopy (SAM) is a suitable methodology for investigating elastic properties of the urethra, and that it can be used to correlate elastic properties to histological areas. One 40 kg female pig and one 2 kg male rabbit comprised the material. A SAM2000 was used at a working frequency of 1000 MHz. Sections of nominal 3 micrometer thickness fixed urethral tissue were prepared for SAM and stained for light microscopy. The histological layers of the urethra were evident in the SAM image, and showed highly variable values of elastic properties. The layers seen with SAM correlated well with those seen with light microscopy. In conclusion, we have provided the first images of the microelastic properties of the urethra and correlated them to histology.

Four years ago Kojima and coworkers discovered ghrelin. Within this short lifespan ghrelin has become one of the "hottest topics" in metabolic research, and today more than 300 papers have emerged (PubMed search). The huge interest in ghrelin is partly due to its involvement in appetite regulation. Over-nutrition, obesity and type 2 diabetes are major burdens of health services in all Western countries, and the discovery of ghrelin opens for the development of antagonists that may make it possible to control appetite and food intake. At the other end of the nutritional scale, ghrelin agonists may be used in cachexia in e.g. anorexia nervosa and cancer. Thus, the potential clinical value of ghrelin research appears to be enormous. At the time of writing several in-house as well as commercial ghrelin assays have been developed. However, we still need to come to a consensus on measurement of circulating ghrelin levels. Up till now, blood ghrelin has been estimated by use of serum as well as various types of plasma, with or without extraction prior to assay. This may affect both results and conclusions. In the present paper we shall review the current literature on ghrelin, with special focus on measurements in human blood specimens.

The objective of this study was to examine the effect of unilateral ureteral obstruction on the apparent diffusion coefficient (ADC) in pig kidney. Changes in ADC is suggested to reflect changes in the ratio of extracellular to intracellular volume. Thirteen pigs were allocated into three groups: 1) pigs subjected to acute unilateral ureteral obstruction (AUO) (n = 3), 2) pigs subjected to chronic partial unilateral obstruction (CPUO) (n = 3), and 3) control pigs (n = 7). The extra- to intracellular volume ratio was indirectly measured in both the ipsilateral obstructed kidney and contralateral non-obstructed kidney by the ADC of the renal tissue using diffusion-weighted echo-planar magnetic resonance imaging. ADC was 2.07 +/- 0.27 x 10(-3) mm2/s in the cortex and 2.10 +/- 0.24 x 10(-3) mm2/s in the medulla of normal control kidneys. In the obstructed kidney from the AUO group the ADC of the medulla was significantly reduced 24 hours after occlusion of the ureter (1.65 +/- 0.05 x 10(-3) mm2/s vs 2.10 +/- 0.24 x 10(-3) mm2/s; p < 0.05). Similarly ADC decreased slightly in the cortex of the ipsilateral kidney. In contrast, ADC of the ipsilateral kidney of CPUO pigs was increased both in the renal medulla (3.13 +/- 0.21 x 10(-3) mm2/s vs. 2.10 +/- 0.24 x 10(-3) mm2/s; p < 0.05) and cortex (3.09 +/- 0.14 x 10(-3) mm2/s vs. 2.07 x 10(-3) mm2/s, p < 0.05). In conclusion, the results of the present study suggest that diffusion weighted imaging (ADC) may be a useful parameter to incorporate when identifying whether a ureteric obstruction is acute or chronic.