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J Smits

Publications and source records attributed to J Smits.

At least 19 recordsLinked to original sources
PubMed2003

Histocompatibility and corneal transplantation.

BACKGROUND: HLA typing and matching have been poorly implemented in corneal transplantation, mainly because of inconclusive or contradictory analytical results. Consequently, we studied the immune response of corneal transplant recipients to HLA histoincompatibilities in a large homogeneous study. METHODS: All corneal transplantations were performed by a single surgeon in a single center between 1976 and 1996. Population genetic and other statistical analyses were performed. Simulation studies assessed the effects of HLA-DR mistypings on analytical results. RESULTS: Mono- and multivariate analyses identified retransplantation, degree of vascularization, HLA-AB and -DR match grades, endothelial cell count, graft size, recipient gender, storage method and panel-reactive antibodies as significantly influencing the survival of corneal transplants. Simulation studies showed that the beneficial effect of HLA-DR matching is abrogated by HLA-DR mistypings. CONCLUSIONS: Corneal transplant recipients have a normal immune response to HLA incompatibilities. Demonstration of that fact requires accurate HLA typings.

Cell Count↗
PubMed2002

Socioeconomic status of very small areas and stroke incidence in the Netherlands.

OBJECTIVE: To examine whether characteristics of very small living areas can be used to predict disease incidence and to use these characteristics to assess socioeconomic differences in stroke incidence in the Netherlands. DESIGN: Characteristics of postcode areas of stroke patients are compared with characteristics of postcode areas of all individual people in the study region, using Poisson regression analysis. SETTING: Six provinces of the Netherlands, covering about half of the country. PATIENTS: 760 patients who in 1991 or 1992 were consecutively admitted because of stroke to 23 Dutch hospitals. MAIN RESULTS: Stroke incidence is significantly higher among people living in postcode areas with below average socioeconomic status (relative risk=1.27; 95% confidence intervals 1.08 to 1.51) and among people living in postcode areas with predominantly older inhabitants (RR=3.17; 95% CI=2.29 to 4.39). It is also significantly increased in more urbanised areas compared with the countryside, the highest incidence being found in the large cities (RR=1.78; 95% CI=1.31 to 2.44). CONCLUSIONS: A clear socioeconomic gradient in stroke incidence in the Netherlands is observed, with people living in detailed postcode areas with below average socioeconomic status experiencing a significantly higher risk of stroke. The analysis also confirms that characteristics of detailed postcode areas can effectively be used to differentiate between areas with and areas without stroke patients.

Adult↗
PubMed2002

Chronic measurement of cardiac output in conscious mice.

We describe the feasibility of chronic measurement of cardiac output (CO) in conscious mice. With the use of gas anesthesia, mice >30 g body wt were instrumented either with transit-time flow probes or electromagnetic probes placed on the ascending aorta. Ascending aortic flow values were recorded 6-16 days after surgery when probes had fully grown in. In the first set of experiments, while mice were under ketamine-xylazine anesthesia, estimates of stroke volume (SV) obtained by the transit-time technique were compared with those simultaneously obtained by echocardiography. Transit-time values of SV were similar to those obtained by echocardiography. The average difference +/- SD between the methods was 2 +/- 7 microl. In the second set of studies, transit-time values of CO were compared with those obtained by the electromagnetic flow probes. In conscious resting conditions, estimates +/- SD) of cardiac index (CI) obtained by the transit-time and electromagnetic flow probes were 484 +/- 119 and 531 +/- 103 ml x min(-1) x kg body wt(-1), respectively. Transit-time flow probes were also implanted in mice with a myocardial infarction (MI) induced by ligation of a coronary artery 3 wk before probe implantation. In these MI mice (n = 7), average (+/- SD) resting and stimulated (by volume loading) values of CO were significantly lower than in noninfarcted mice (n = 15) (resting CO 16 +/- 3 vs. 20 +/- 4 ml/min; stimulated CO 20 +/- 5 vs. 26 +/- 6 ml/min). Finally, using transfer function analysis, we found that, in resting conditions for both intact and MI mice, spontaneous variations in CO (> 0.1 Hz) were mainly due to those occurring in SV rather than in heart rate. These data indicate that CO can be measured chronically and reliably in conscious mice, also in conditions of heart failure, and that variations in preload are an important determinant of CO in this species.

Animals↗
PubMed2000

Beneficial effect of HLA-DR matching on the survival of corneal allografts.

BACKGROUND: Although HLA typing and matching have been used for 3 decades, that practice has been poorly implemented in corneal transplantation, mainly because of inconclusive or contradictory analytical results. Consequently, we studied the immune response of corneal transplant recipients to HLA histoincompatibilities in a large homogeneous study. METHODS: All corneal transplantations performed by a single surgeon between 1976 and 1996 were studied. HLA-AB matching was used for recipient selection. All HLA typings were performed by a single experienced laboratory. Population genetic techniques were used to assess the validity of the HLA typings. Mono- and multivariate analyses were performed to identify the factors which significantly influence the survival of corneal allografts. Simulation studies were carried out to demonstrate the effects of mis-typed donor and recipient HLA-DR typings on analytical results. RESULTS: Retransplantation, degree of vascularization, HLA-AB and DR matching, endothelial cell count, graft size, recipient gender, and storage method were identified as significant factors by our monovariate analyses. A Cox proportional hazards survival analysis model identified degree of vascularization and HLA-AB and DR matching as significant prognostic factors when all immunological rejection episodes were used, P=0.000001. When only irreversible immunological rejection episodes were used, panel reactive antibodies, retransplantation, and number of rejection events were also identified, P=0.000001. Simulation studies showed that the effects of HLA-DR matching are abrogated by poor HLA-DR typings. CONCLUSIONS: Corneal allograft recipients have a normal alloimmune response to histoincompatibilities. Demonstration of that fact requires accurate HLA typings.

Adolescent↗
PubMed2000

Disruption of the plasminogen gene in mice abolishes wound healing after myocardial infarction.

The plasminogen system plays an important role in the proteolytic degradation of extracellular matrices during wound healing. In the present study we investigated the impact of the plasminogen system on cardiac wound healing and function after myocardial infarction. Myocardial infarction was induced in plasminogen-deficient mice (Plg-/-) and in wild-type controls (Plg+/+). Structural analysis 1, 2, and 5 weeks after infarction revealed that infarct healing was virtually abolished in Plg-/- mice, indicating that the plasminogen system is required for the repair process of the heart after infarction. In the absence of plasminogen, inflammatory cells did not migrate into the infarcted myocardium. Necrotic cardiomyocytes were not removed and the formation of granulation tissue and fibrous tissue did not occur. In these non-healing infarcted hearts, LV dilatation was not altered. In addition, gelatinolytic activity of MMP-2 and MMP-9 was depressed in the Plg-/- infarcted hearts, suggesting that the plasmin effect on infarct healing may be mediated by MMPs. Surprisingly, cardiac function was only attenuated to a rather small extent in the Plg-/- infarcted mice when compared to the wild-types. This study provides direct prove that plasmin-mediated proteolysis plays a central role in cardiac wound healing after myocardial infarction in mice.

Animals↗
PubMed1998

Kidney transplantation from living unrelated donors.

Our center activated our living-related donor (LRD) kidney transplantation program in 1967 and the living-unrelated donor (LURD) kidney transplantation program in 1968. We performed 62 kidney transplants (of which 6 were LURD) under conventional immunosuppression therapy of the period. During the cyclosporine era, our group performed the first living-donor kidney transplant in 1982 and the first LURD transplant in Europe in 1983. Since then 184 LURD transplants (1/3 of all living kidney transplants) took place in our center under cyclosporine therapy. LURD remains a controversial procedure as a consequence of problems related both to the donor's risk, which can be reduced by careful medical evaluation and selection, and to the recipient's outcome, including the importance of HLA compatibility, as well as concerns about the danger of commercialism. According to international evidence, as well as our own experience, LURD kidney transplantation is a safe and effective approach to increase the donor pool. Living donor mortality is extremely low, while long-term graft survival is the same as that observed after LRD transplantation and is superior to that for cadaver donor transplantation. We do not recommend DST because the long-term survival benefits do not justify the risks of sensitization and infections. At least for primary transplants, there is not an increased risk of transplantation from a husband to his wife with previous pregnancies. The pretransplant screening of taboo HLA mismatches could be useful to increase long-term graft survival. It is our opinion that LURD transplantation should be considered at least as good a clinical option as cadaver donor transplantation for patients with end-stage renal failure. A selective advantage of this procedure is that dialysis could be avoided before transplantation, with significant socio-economic benefits and improved recipient quality of life.

Adult↗
PubMed1996

Neuropeptide Y-enhanced diuresis and natriuresis in anaesthetized rats is independent of renal blood flow reduction.

1. Neuropeptide Y (NPY) has been reported to enhance diuresis and natriuresis in anaesthetized rats although it is a potent renal vasoconstrictor in vitro in vivo in several species. Therefore, we have investigated anaesthetized rats to see whether reduction in renal blood flow (RBF) and enhancement of diuresis and natriuresis can occur concomitantly, and how diuresis and natriuresis might be enhanced despite reduced RBF. 2. Systemic or intrarenal NPY infusion (0.03-3 micrograms kg-1 min-1) had only a small effect on mean arterial pressure (maximal increase 15-20 mmHg) and heart rate (maximal decrease 30 beats min-1) but dose-dependently reduced RBF (maximal peak reduction 3 ml min-1) Endogenous creatinine clearance was not significantly altered. 3. In anaesthetized rats systemic infusion of 1 or 3 micrograms kg-1 min-1 NPY enhanced urine formation and sodium and calcium excretion by a maximum of 110, 110 and 45%, respectively, but did not alter potassium excretion. Enhancement of diuresis was also detectable in conscious rats. 4. The diuretic and natriuretic effects of systemically infused NPY were at least partly maintained in rats with decapsulated kidneys and in rats where NPY-induced increase of renal perfusion pressure was excluded mechanically by an adjustable clamp placed on the abdominal aorta. 5. Intrarenal infusion of 0.3 or 1 microgram kg-1 min-1 NPY reduced RBF to a greater extent than systemic infusion (maximal peak reduction 4 ml min-1) but caused a smaller enhancement or even a reduction of urine formation and sodium excretion. 6. We conclude that systemic infusion of NPY reduces RBF by a direct effect on the renal vasculature. Systemic NPY infusion enhances urine formation and sodium and calcium excretion. This occurs independently (at least in part) of pressure natriuresis by formation and/or release of an extrarenal factor which might act on distal tubules and/or collecting ducts.

Anesthesia, General↗
PubMed1993

Inhibition of angiotensin-converting enzyme reduces urinary albumin excretion but not regional albumin clearance in experimental diabetes.

Albuminuria and increased regional albumin clearance are known to develop concomitantly in diabetes. The anti-proteinuric effect of angiotensin-converting enzyme inhibitor therapy is well established. We studied whether angiotensin-converting enzyme inhibitor therapy with perindoprilat in comparison with conventional antihypertensive treatment could influence the development of increased regional albumin clearance as well as albuminuria in experimental diabetes. Rats with streptozotocin-induced diabetes were randomized into a saline group (n = 7), a perindoprilat (1 mg/kg per day) group (n = 8), and a hydralazine (3 mg/kg per day) group (n = 6); six rats served as non-diabetic controls. After 6-8 weeks, blood pressure was equally reduced in the perindoprilat- and hydralazine-treated groups (P < 0.01). Twenty-four-hour urinary protein and albumin excretion were increased in diabetic rats compared to control rats (P < 0.001). Hydralazine did not reduce 24 h protein or albumin excretion, whereas perindoprilat treatment reduced both (P < 0.001) to levels comparable to those of control rats. Regional albumin clearance, assessed in the eye, ileum, lung, skeletal muscle and skin, was clearly elevated in diabetic rats compared to control rats; however, neither drug therapy had an effect on albumin clearance.

Albumins↗
PubMed1993

A double-blind study comparing safety, tolerability and efficacy of iodixanol 320 mgI/ml and ioxaglate 320 mgI/ml in cerebral arteriography.

Iodixanol is a new nonionic dimer, isotonic with blood at all concentrations. Iodixanol 320 mgI/ml was compared in a double-blind, randomized study to the ionic dimer ioxaglate 320 mgI/ml for evaluation of safety and efficacy parameters during cerebral arteriography. Eighty adult patients were enrolled and all completed the trial. Radiographic efficacy was assessed from the diagnostic information and the radiographic density. Safety was evaluated by recording discomfort and other adverse events, changes in ECG, heart rate and blood pressure, changes in intra-arterial blood pressure and circulation time. No difference between the two contrast media were noted radiographically. No clinically important changes from baseline or between the two contrast media were found in ECG, heart rate, blood pressure or intra-arterial blood pressure. Although not statistically significant, a somewhat longer mean circulation time was found with iodixanol, probably due to its slightly higher viscosity. Injection-associated warmth sensation and pain were more intense with ioxaglate than with iodixanol, and pain was statistically more frequent after injection of ioxaglate. A high incidence of adverse events other than discomfort is reported in this study, mainly related to the selective arteriographic procedure itself. The adverse events related to the contrast medium were more frequent with ioxaglate (27% of the total number of adverse events) than with iodixanol (10%). The new isotonic nonionic dimer iodixanol offers significantly better comfort to the patient than does ioxaglate. This is an important feature, especially in relatively risky procedures that are unpleasant for the patients, such as conventional cerebral angiography.

Adolescent↗
PubMed1992

Microplate washing: process description and improvements.

Heterogeneous immunoassays require wash steps in order to separate bound from free constituents. In this paper we demonstrate that in microplate assays the washing process includes two separate physical processes: (1) a rapid and wash volume-dependent direct dilution of the droplet-shaped residual volume, and (2) a diffusion-limited and strongly time-dependent dilution of a residual layer of liquid, which necessitates the use of time-consuming soak times in the immunoassay. We have shown that optimizing the motion of the wash fluid effectively reduces the residual layer thickness that results in extended soak times. This results not only in improved washing efficiency and reduced background variance in the immunoassay, it also yields a significantly improved immunoassay sensitivity.

Immunoassay↗
PubMed1992

Mortality of fallow deer (Dama dama) experimentally-infected with meningeal worm, Parelaphostrongylus tenuis.

Six fallow deer (Dama dama) fawns died after receiving 25 to 150 infective larvae of Parelaphostrongylus tenuis. Fawns given higher doses usually died sooner (6 to 23 days) than those given lower doses (54 to 67 days). Early deaths were associated with severe acute peritonitis resulting from perforation of the intestinal wall; later deaths were associated with paralysis and inability to rise. Numerous adult P. tenuis were found within neural tissues of the brain and spinal cord in the three fawns with paralysis. One white-tailed deer (Odocoileus virginianus) exposed to infective larvae from the same source survived infection without exhibiting clinical signs and began passing larvae in feces 88 days post-exposure. At the doses used in this study, meningeal worm caused fatal infections in fallow deer. Results are compared to published observations of fallow deer naturally-infected with P. tenuis.

Abomasum↗
PubMed1991

Cyclical Cushing's disease. A case report.

A 41-year-old man with clinical Cushing's syndrome and intermittent central ACTH hypersecretion for a period of 9 1/2 years follow-up is described. Episodes of biochemical and clinical remission alternated with periods of florid Cushing's disease, characterized by circadian hyperpulsatile ACTH and cortisol secretion. Responses to metyrapone and inhibition of ACTH and cortisol hypersecretion after high dose dexamethasone during active phases of the disease favored a central origin of ACTH hypersecretion, confirmed by simultaneous bilateral venous sampling of the sinus petrosus inferior. Prolonged clinical remission followed near total anterior hypophysectomy. However, on anatomopathological examination of the pituitary neither corticotroph cell hyperplasia nor a microadenoma could be documented. The possibility of a functional ACTH hypersecretion is discussed.

Adrenal Glands↗
PubMed1989

Tyrosine kinase activity in breast cancer, benign breast disease, and normal breast tissue.

Tyrosine specific protein kinase activity was determined in 70 specimens of the human mammary gland. These included 28 cancers of the breast, 21 benign breast diseases, and 21 normal breast tissues. We measured tyrosine kinase activity in the cytosol fraction and in the membrane fraction of the homogenates. In addition cytosolic aldolase activity was measured. Tyrosine kinase activity was determined using poly(glutamic acid:tyrosine = 4:1) as an artificial substrate. Cancers of the breast exhibited considerable higher tyrosine kinase activities in both cytosol and membrane fractions, compared to benign breast tumors (P less than or equal to 0.001). Benign tumors demonstrated increased activities in cytosol in comparison to normal breast tissues (P less than 0.001). Furthermore, there appears to be a strong association of an enhanced expression of activity of tyrosine kinase in cytosol of primary carcinomas and early systemic relapse. In combination with aldolase activity a nearly complete discrimination is achieved between malignant specimens on one hand and benign and normal tissues on the other.

Adult↗
PubMed1988

Heterogeneity of glycolytic enzyme activity and isozyme composition of pyruvate kinase in breast cancer.

In 6 patients with breast cancer - of whom specimens of the primary tumor as well as one of its metastases were available for examination - we demonstrated intratumoral and intertumoral heterogeneity in expression of activity of the glycolytic enzymes hexokinase, phosphofructokinase, aldolase, enolase and pyruvate kinase. Heterogeneity also existed in isozyme composition of pyruvate kinase. The transition of the tumors towards normal surrounding breast tissue showed either a sharp drop in activity, or a gradual decrease in activity, corresponding to pushing margins or infiltrative growth of the tumor as was demonstrated by histologic examination of these specimens. Likewise, the shift towards expression of K isozyme of pyruvate kinase in breast cancer compared to normal breast tissue could be demonstrated.

Adult↗