APMIS. Supplementum最新文献

It must be assumed that all tumor cells produce proteins which do not belong to a normal cell. These are called tumor-associated or tumor-specific antigens. In the classic immune surveillance theory it is believed that the cellular immune defense (the T-cell system) continuously discovers and eliminates newly arisen tumor cells which express such tumor-specific antigens. Since then it has been shown that one of the preconditions for the T-cell system to be able to recognize antigens is that they are presented by MHC class I histocompatibility antigens. There is a continual processing and presentation of all intracellular proteins in a cell. Thus, a tumor cell which produces an abnormal protein will also present this and thereby expose itself to being killed by cytotoxic T cells. The antigens are presented in the form of short peptides (8-9 aminoacids), which arise as a result of controlled degradation of the original proteins. The peptides thus formed are transported by specialised molecules in the so-called endogenous antigen processing and presentation pathway, and are eventually bound to and presented by MHC class I molecules. It has been shown that many tumors express less MHC class I on their surface compared to the normal tissue from which they have arisen, and also that patients with reduced immune function have an increased incidence of certain forms of cancer. It is therefore widely believed that a low MHC class I level contributes to the ability of tumor cells to avoid the T-cell-mediated immune defense. The aim of the present research project was to confirm the existence of a T-cell-mediated immune selection in primary tumors. Another of its goals was to elucidate the extent to which tumor cells with low MHC class I expression showed poor ability to present antigen, and whether the reason for this could be found in one or more of the molecular systems which participate in antigen processing and presentation. By using the chemical carcinogen 3-methylcholanthrene a total of 144 tumors were induced in immunologically normal and T-cell defective mice, respectively. It was assumed that tumors induced in normal mice would be immune selected, whilst this would not be the case for tumors from T-cell defective mice. This enabled us to work with a tumor-material where the two populations only differed in that the one part had undergone selection by a T-cell system and the other had not. Tumor induction time turned out to be shorter in immune defective than in normal mice, and the tumor frequency was higher, which might be due to the fact that in normal mice tumor growth was inhibited and in certain cases stopped by the T cells. On transplantation of the uncloned cell lines which were established from the primary tumors to immunologically normal congenic recipients, we were able to show that most of the tumors which originated from mice with a functional T-cell system, and which must therefore be assumed to have undergone selection in the p

We present an overview of the fast development of less invasive techniques in intrarenal surgery all based on percutaneous nephrostomy. Life-long urinary diversion with nephrostomy is often necessary in patients with malignant disease and such patients have more postnephrostomy complications than patients with kidney stones and their survival is short. In a follow-up of 246 patients with 275 nephrostomies performed consecutively over two years, mean survival after urinary diversion was only 7.9 months in 38 prostate cancer patients with ureteral obstruction and only 5.3 months in 20 patients with advanced bladder cancer. We emphasize the necessity of informing the patient and his/her family of the expected outcome of the procedure and the importance of using carefully chosen and realistic indications.

Ischaemic preconditioning (IP) is a strong endogenous infarct reducing stimulus which has not previously been evaluated with myocardial perfusion imaging using 99mTc-MIBI. Factors responsible for cellular MIBI uptake are affected by both IP and acute ischaemia (plasma membrane and mitochondrial membrane potential and oxidative metabolism). IP seems to involve mitochondrial K-ATP channels affecting mitochondrial membrane potential and thereby potentially MIBI uptake. The study evaluated the performance of MPI with MIBI as a tracer to characterise the extent that severely ischaemic compromised myocardium was salvaged by IP. In a closed chest model, an ischaemic preconditioned group (8 pigs) subjected to IP before introducing a 45 min period of catheter based coronary occlusion was compared with a control group (9 pigs). Area at risk'(AAR), infarct size (IS) and IS relative to AAR was determined by MIBI SPECT and by a standard histochemical method. The results demonstrated that infarct size was significantly smaller in the IP group both relative to left ventricle (IS/LV) and to area at risk (IS/AAR). Both AAR/LV and IS/LV, however, were greater when measured by MPI than with histochemistry. There was no difference in the ratio between infarct size and area at risk (IS/AAR). In conclusion, MPI with MIBI is a reliable measurement of infarct reduction by ischaemic preconditioning. Myocardium affected by recent ischaemia is correctly distinguished as viable by MPI in early reperfusion, when compared to a standard histochemical technique.

The phenotype of cryopreserved crossbred porcine PBMC, with special emphasis on NK cell related surface markers, was characterised. The phenotype expressed prior to stimulation with rHu IL2 and rHu IL12 was related to the in vitro cytotoxic capacity estimated in a 4-h or 21-h 51Cr-release assay. PBMC incubated in growth medium without addition of cytokines were used to investigate the spontaneous cytotoxic capacity. The results of this study suggest that crossbred porcine PBMC comprise a specific subset expressing the phenotype CD2+CD3-CD4-CD8+SWC3-CD16+CD21-. No spontaneous cytotoxicity of the PBMC could be estimated, but the expression of CD16 seems to be a basic marker of the cytokine induced cytotoxic activity. This study suggests that cryopreserved porcine PBMC can be used when possible influences on the porcine NK cell system are investigated in relation to disease models conducted experimentally in crossbred pigs.

Hydronephrosis is generally considered a pathologic process, and especially in infancy is widely viewed as caused by obstruction, potentially injurious to the kidney and in need of expeditious surgical treatment. However a number of clinical and experimental studies suggest exactly the opposite: that hydronephrosis is not pathological but actually a compensating mechanism designed to protect the kidney from high pressures and renal damage. Furthermore, because hydronephrosis in the infant involves an already compliant and distensible renal pelvis it appears to be uniquely beneficial. Herein the experimental basis for a counterargument challenging the harmful effects of hydronephrosis will be presented.

A urodynamic characterization of the distinctive patterns of normal micturition in man and rat was undertaken. Data were obtained from experimental studies where bladder pressure was measured suprapubically obviating urethral instrumentation. Ambulatory urodynamic studies were conducted with 17 asymptomatic male volunteers. Bladder pressure was monitored via a supra-pubic catheter and abdominal pressure via a rectal balloon using a UPS2020 ambulatory system. Average duration of each monitoring period was 20.5 hours. Detrusor pressure and flow rate records from each subject were identified and consecutive filling and voiding phases were averaged over the entire monitoring period using the onset of micturition as a time marker. The averaged pattern of pressure, flowrate, cumulative volume, and contractility curves for each subject as well each for group was computed and graphically presented. For comparison, the micturition phase of 18 anesthetized rats were used. A continuous CMG was performed and bladder pressure was recorded suprapubically. For each group the averaged parameters of urethral opening pressure, Max Detrusor pressure, Detrusor pressure at Max flowrate, bladder capacity, and WF were extracted and compared statistically. Numerical values are M +/- SE. The urodynamic temporal patterns observed during the micturition phase of the CMG in terms of detrusor pressure and associated flow, in both man and rat posses striking qualitative similarities. These are particularly striking during the onset of micturition in the great majority of animals. Furthermore the pressures generated by the bladder before and during micturition are quantitatively similar. However there were also distinct differences particularly in the pattern observed during voiding when bladder pressure was oscillatory. The temporal sequence of detrusor pressure and flow in man and rat contains many qualitative and quantitative similarities rendering the rat's potential as a particularly useful model in the study of the onset of micturition.

The discovery of aquaporin-1 (AQP1) by Agre and colleagues explained the long-standing biophysical question of how water specifically crosses biological membranes. These studies led to the discovery and identification of a whole new family of membrane proteins, the aquaporins. At present, at least seven aquaporins are expressed at distinct sites in the kidney and 4 members of this family (AQP1-4) have been demonstrated to play pivotal roles in the physiology and pathophysiology for renal regulation of body water balance. Osmotic equilibration via renal aquaporins is maintained by active transport of NaCl. The major sodium transporters and channels in the individual renal tubule segments have been identified and the regulation of these transporters and channels are fundamental for renal sodium reabsorption and for establishing the driving force. In this mini-review the role of renal aquaporins and sodium transporters and channels is briefly described and their key role for the impaired urinary concentrating capacity in response to urinary tract obstruction is reviewed. Thus this review updates previous detailed reviews (1-5).

Autosomal dominant familial neurohypophyseal diabetes insipidus (adFNDI) is a rare disorder caused by progressive postnatal arginine vasopressin (AVP) deficiency resulting from mutations in the AVP gene encoding the AVP pre-prohormone. It has been suggested that these mutations exert their effect on the cellular handling of the AVP prohormone by leading to the synthesis of mutant hormone precursor that fails to be processed and/or folded properly in the endoplasmic reticulum (ER). As a consequence, it is retained by the ER protein quality control machinery resulting in protein accumulation and initiation of cellular processes leading to degeneration of the AVP producing neuron. This review summarizes the current knowledge on adFNDI and discusses different hypotheses concerning its pathogenesis.

This report covers the outcome of the first three invitation rounds of the organised mammography screening programme in the county of Fyn. The programme started in November 1993, and the third invitation round ended on 31 December 1999. The screening takes place either at a special clinic located at University Hospital Odense or in a mobile unit. Women living in and around the city of Odense are examined at the clinic (about 55%), while the rest are examined in the mobile unit. Two-view mammography is used at the first screening. Women with dense breast tissue will continue to have two-view mammography (about 60%), whereas the rest will have singleview mammography at the subsequent screens. All screening images are exposed at the mammography-screening clinic and evaluated with double reading in the clinic. The programme targets women aged 50-69, except those undergoing treatment for breast cancer or going for regular check-ups following breast cancer. Based on the updated population register, the IT-Centre of the county of Fyn issues the invitations. Invited are all women aged 50-69 and living in the county of Fyn when their general practitioners' patients are invited. During the first 3 invitation rounds, 136,079 screening tests were made. Of these, 129,375 tests were made in the women aged 50-69 targeted by the programme. In addition, 6682 screening tests were made in women aged 70 and above, and 22 screening tests were made in women below the age of 50. As a consequence of the mammography screening 2657 assessments were made, 1145 women had surgery, 782 women were diagnosed with invasive breast cancer, and 109 women were diagnosed with ductal carcinoma in situ. A participation rate for the first invitation round was calculated immediately after the end of the round based on the number of participants divided by the number of women invited. This percentage was 88%. Invitation data are, however, not stored. It is therefore not possible now to calculate the participation rates in previous invitation rounds based on the same method. We have therefore chosen to calculate the participation rate as the coverage, i.e. the number of participants divided by the average number of women in the county of Fyn during a given invitation round. Calculated in this way, 84% participated in the first round, 84% in the second round, and 82% in the third round. It should be remembered that these figures do not take into account that some women are not invited because they 1) were undergoing current treatment for breast cancer or going for regular check-ups following breast cancer, or 2) did not participate in the previous round (and never actively informed the programme that they wanted an invitation to the next invitation round), relevant only for the second and third invitation round. For the second and third invitation rounds, the programme only invited women who participated in the previous invitation round, asked the clinic for an invitation, or entered

The aim of this study was to elucidate the relation between pelvic pressure and bladder pressure during pelvic perfusion with standardized flow rates. Anaesthetized Danish Landrace Breed pigs (n = 5) weighing 35-40 kg were studied. Transparenchymally two 6-F catheters were placed in both renal pelves for pressure measurement and perfusion. Transurethrally two catheters were placed in the bladder for pressure measurements and for urine collection and infusion. Bladder filling was done with a constant infusion rate of 45 ml/min during perfusion of both pelves with saline consecutively with the flow rates: 0, 2, 4, 6 and 8 ml/min during continuous measurement of bladder and bilateral pelvic pressure. The baseline diuresis varied from 0.4-1.0 ml/min. Without pelvic perfusion a negative pressure gradient between pelvis and bladder was seen demonstrating the importance of ureteral peristalsis. Pelvic perfusion with 2 ml/min showed that pelvic and bladder pressure were equal demonstrating weakening of ureteral peristalsis. During perfusion with higher flow rates pelvic pressure was higher than bladder pressure, showing that the positive gradient was important for urine transport. In conclusion ureteral peristalsis is important at low flow rates during increasing bladder pressure. At higher flow rates peristalsis weakens and the pressure gradient is the determining factor.