Biomedical subjects

G Kramer

Publications and source records attributed to G Kramer.

At least 19 recordsLinked to original sources

PubMed2006

Docetaxel induces apoptosis in hormone refractory prostate carcinomas during multiple treatment cycles.

Caspase-cleaved proteins are released from disintegrated apoptotic cells and can be detected in the circulation. We here addressed whether caspase-cleaved cytokeratin 18 (CK18-Asp396) can be used as a serum biomarker for assessment of the clinical efficiency of chemotherapy in hormone-refractory prostate cancer (HRPC). A total of 82 patients with HRPC were evaluated during 751 treatment cycles, either with estramustine (EMP)/vinorelbine or with EMP/docetaxel. The levels of CK18-Asp396 and of total CK18 were measured in patient serum before and during therapy by ELISA. Docetaxel induced significant increases in serum CK18-Asp396 (P<0.0001) and total CK18 (P<0.0002), suggesting induction of apoptosis. Similarly, vinorelbine induced increases in both CK18-Asp396 and CK18 (P<0.001 and 0.011). In contrast, EMP induced increases in total serum CK18 (P<0.0001), but not in CK18-Asp396 (P=0.13). The amplitudes of docetaxel-induced increases were associated with baseline prostate-specific antigen (PSA) and CK18 serum levels in these patients, consistent with tumoral origin of caspase-cleaved fragments. Docetaxel induced significant increases in CK18-Asp396 during second-, third- and fourth-line therapy and induced increased levels of CK18-Asp396 during treatment cycles 1-8. In contrast, vinorelbine induced significant increases only during cycles 1-3. In a subgroup of 32 patients that received EMP/vinorelbine in second line followed by EMP/docetaxel in third line, docetaxel induced stronger increases than vinorelbine (P=0.008). These results show that the CK18-Asp396 serum marker can be used to assess tumour apoptosis in vivo and suggest that the clinical efficiency of docetaxel in HRPC is due to induction of apoptosis during multiple treatment cycles.

Aged↗

PubMed2006

Overweight, obesity and elevated blood pressure in children and adolescents.

OBJECTIVE: Since many years in adults associations between dyslipidaemia, increased insulin resistance, arterial hypertension and the risk for cardiovascular diseases have been recognized. It was the aim of the present trial to investigate these associations and interactions between height, weight, body-mass index and blood pressure values in overweight/obese and normal weight children and adolescents. PATIENTS AND METHODS: 172 children and adolescents (n = 86 with overweight and obesity, n = 86 controls) were studied. In all the subjects anthropometrical data and blood pressure values were assessed. RESULTS: Overweight and obese children had significantly higher blood pressure values (systolic 117.9 +/- 9.7, diastolic 75.6 +/- 8.8 mmHg) than control subjects (systolic 111.4 +/- 11.0, diastolic 69.5 +/- 8.8 mmHg, p<0.001/0.001). Additionally in overweight and obese subjects the number of patients with blood pressure values below the 50th percentile was lower, but the numbers of children and adolescents with values >or=50th age-, height- and gender-specific percentiles were significantly higher. In multivariate analysis of overweight/obese children and adolescents only patients' BMI (R-square = 0.26, beta = 0.52, p<0.001), but not sex, age, height or weight revealed any association with systolic blood pressure values. Diastolic blood pressure revealed an association with childrens' and adolescents' weight (R-square = 0.22, beta = 0.48, p<0.001), but there were no associations with body-mass index, sex, age or height. In normal weight control subjects age (beta = 0.32, p = 0.01) and height (beta = 0.28, p = 0.03) showed associations with the systolic blood pressure values (R-square = 0.15), but only childrens' and adolescents' height (beta = 0.39, p<0.001) was associated with diastolic blood pressure (R-square = 0.28). CONCLUSIONS: Overweight and obesity in childhood are highly associated with multiple comorbidities, elevated blood pressure values, dyslipidaemia, reduced insulin sensitivity and alterations of large and minor vessels. Overweight and obesity in children and adolescents should not longer be regarded as variations of normality, but as diseases with an extremely high risk for the development of atherosclerosis and cardiovascular complications in adulthood. Knowledge of these complex associations implicate even in young age the need for intervention.

Adolescent↗

PubMed2006

Are there potential problems with generic substitution of antiepileptic drugs? A review of issues.

In response to increasing cost pressures, healthcare systems are encouraging the use of generic medicines. This review explores potential problems with generic substitution of antiepileptic drugs (AEDs). A broad search strategy identified approximately 70 relevant articles. Potential problems with generic substitution included: The limited evidence (mainly case reports with some pharmacokinetic studies) appears to support these concerns for older AEDs. As a result, restrictions on use of specific generic AEDs are in place in some countries and recommended by some lay epilepsy organisations. As more AEDs lose patent protection, it is important to examine the question of whether generic substitution may pose problems for patients with epilepsy, and whether there should be safeguards to ensure that both physician and patient are informed when generic substitution occurs.

Anticonvulsants↗

PubMed2006

Reconciling open-charm production at the Fermilab Tevatron with QCD.

We study the inclusive hadroproduction of D0, D+, D*+, and D(s)+ mesons at next-to-leading order in the parton model of quantum chromodynamics endowed with universal nonperturbative fragmentation functions fitted to e+e- annihilation data from CERN LEP1. Working in the general-mass variable-flavor-number scheme, we resum the large logarithms through the evolution of the fragmentation functions and, at the same time, retain the full dependence on the charm-quark mass without additional theoretical assumptions. In this way, the cross section distributions in transverse momentum recently measured by the CDF Collaboration in run II at the Fermilab Tevatron are described within errors.

Journal Article↗

PubMed2005

Generalizing the Dokshitzer-Gribov-Lipatov-Altarelli-Parisi evolution of fragmentation functions to the smallest values.

An approach valid to any order which unifies the fixed order Dokshitzer-Gribov-Lipatov-Altarelli-Parisi evolution of fragmentation functions at large x with soft gluon logarithmic resummation at small x is proposed. At lowest order, this approach, implemented with the double logarithmic approximation, reproduces exactly the modified leading logarithm approximation but is more complete due to the degrees of freedom given to the quark sector and the inclusion of the fixed order terms. We find that data from the largest x values to the peak region can be better fitted than with other approaches.

Journal Article↗

PubMed2005

Low temperature of GroEL/ES overproduction permits growth of Escherichia coli cells lacking trigger factor DnaK.

Escherichia coli trigger factor (TF) and DnaK cooperate in the folding of newly synthesized proteins. The combined deletion of the TF-encoding tig gene and the dnaK gene causes protein aggregation and synthetic lethality at 30 degrees C. Here we show that the synthetic lethality of deltatigdeltadnaK52 cells is abrogated either by growth below 30 degrees C or by overproduction of GroEL/GroES. At 23 degrees C deltatigdeltadnaK52 cells were viable and showed only minor protein aggregation. Overproduction of GroEL/GroES, but not of other chaperones, restored growth of deltatigdeltadnaK52 cells at 30 degrees C and suppressed protein aggregation including proteins >/= 60 kDa, which normally require TF and DnaK for folding. GroEL/GroES thus influences the folding of proteins previously identified as DnaK/TF substrates.

Chaperonin 10↗

PubMed2005

Morbidity and mortality in the surgery arm of EORTC 08941 trial.

Controversial results of surgical treatment after induction chemotherapy, especially in relation to the extent of resection, have previously been reported. Mortality and morbidity were studied in the surgical arm of the European Organisation for Research and Treatment of Cancer (EORTC) 08941 trial. EORTC 08941 is a multicentre, prospective, randomised, phase-III trial of surgical resection versus radiotherapy in patients with proven stage IIIA-N2 nonsmall cell lung cancer after an objective response to platinum-based induction chemotherapy. Operative results in the 167 patients randomised in the surgical arm are presented within this study. Among these patients, one switched to the radiotherapy arm and 17 patients did not get any protocol treatment or information is not yet available. Radical resection with negative surgical margins was obtained in 74 patients (49.7%). In 61 patients (40.9%), a pathological down-staging to N0 or N1 was present. Operative 30-day mortality was 4.0%. Post-operative complications were mainly pneumonia, respiratory insufficiency, arrhythmias, air leak, cardiac decompensation, empyema and bronchopleural fistula. In total, 12 (8.1%) patients underwent re-operation due to positive margins, haemothorax, empyema and bronchopleural fistula. In conclusion, surgical resection after induction chemotherapy in the multicentre European Organisation for Research and Treatment of Cancer trial has yielded acceptable rates of morbidity and mortality.

Adult↗

PubMed2004

The differentiation profile of the epithelium of the human lip.

The aim of this study was to analyse the immunohistochemical differentiation profile of the stratified squamous epithelium of the adult human lip. Full-thickness lower lips taken from 31 cadavers were analysed. Sections were stained with haematoxylin and eosin, periodic acid-Schiff (PAS), cytokeratins (CK), loricrin, involucrin, profilaggrin and filaggrin. The stratified squamous epithelium covering the lip could be divided into: (i) appendage-bearing, orthokeratinised epidermis; (ii) orthokeratinised vermilion which had a more prominent rete pattern than the epidermis; (iii) parakeratinised, PAS-positive intermediate zone; and (iv) non- or parakeratinised labial mucosal epithelium. Epithelial thickness increased gradually from the skin to the mucosal aspect. The CK pattern changed across the intermediate zone, with gradual loss of CK 1 and 10 from the skin, and CK 4, 13 and 19 from the mucosal, aspect. CK 5 and 14 were consistently expressed basally, and variably expressed suprabasally. Apart from labelling Merkel cells, CK 8, 18 and 20 were negative. Involucrin, which was present at all sites, was restricted to the stratum granulosum in skin, but extended into the stratum spinosum, and gradually into parabasal keratinocytes, across the vermilion and mucosa. Loricrin, profilaggrin and filaggrin were present in the stratum granulosum of orthokeratinised sites, but expression was abruptly lost at the junction between the vermilion and the intermediate zone. In conclusion, the phenotype of the stratified squamous epithelium covering the lip changes at, or across, the intermediate zone of the adult vermilion. It is possible that changes in the composition of the stratified squamous epithelium affect the colour of the vermilion.

Adult↗

PubMed2004

Fluorescence and ESR studies of the conformational behavior of oppositely charged polyelectrolytes at solid/liquid interfaces.

The conformational behavior of oppositely charged polyelectrolytes on alumina in solutions was investigated by means of excimer fluorescence and electron spin resonance spectroscopy using maleic acid-propene copolymer labeled with pyrene or TEMPO. It was found that the ability of the polyanion at the surface for conformational rearrangements is strongly influenced by the constraints of the adsorbed state that restrict its complexation. Polyelectrolyte complexes (PEC) formed by mixing of the oppositely charged polyelectrolytes exhibited extreme coiling due to the screening of the charged groups. The polyelectrolytes undergo spreading during the adsorption process due to the electrostatic attraction. Surface binding can irreversibly limit the flexibility for the reconformation process to a great extent. It is also shown here that a flatter adsorbed state could be reached by sequential adsorption of polyanion and polycation than could be reached by the direct adsorption of the polyelectrolyte complex itself.

Journal Article↗

PubMed2004

Low temperature or GroEL/ES overproduction permits growth of Escherichia coli cells lacking trigger factor and DnaK.

Escherichia coli trigger factor (TF) and DnaK cooperate in the folding of newly synthesized proteins. The combined deletion of the TF-encoding tig gene and the dnaK gene causes protein aggregation and synthetic lethality at 30 degrees C. Here we show that the synthetic lethality of DeltatigDeltadnaK52 cells is abrogated either by growth below 30 degrees C or by overproduction of GroEL/GroES. At 23 degrees C DeltatigDeltadnaK52 cells were viable and showed only minor protein aggregation. Overproduction of GroEL/GroES, but not of other chaperones, restored growth of DeltatigDeltadnaK52 cells at 30 degrees C and suppressed protein aggregation including proteins >/=60 kDa, which normally require TF and DnaK for folding. GroEL/GroES thus influences the folding of proteins previously identified as DnaK/TF substrates.

Chaperonin 10↗

PubMed2004

[A suggested treatment algorithm in nocturnal enuresis with emphasis on partial responders].

Monotherapeutic strategies often have only partial success in primary nocturnal enuresis (PNE). This analysis evaluated whether adjuvant treatment strategies improve outcomes. PNE children were submitted to a distinct therapeutic strategy including urotherapy (behavioral modifications), a first-line and, if necessary, a second-line treatment period. Outcome was the relief of bedwetting, the follow-up was 3-79 months. Urotherapy was applied. Nonresponders were assigned to desmopressin as first-line treatment. For complete responders a structured withdrawal program was applied. Partial responders were assigned to adjuvant second-line treatment according to their individual symptomatology, masked at basic investigations, incorporating either anticholinergics (propiverine hydrochloride), biofeedback, alpha-blocker (alfuzosin), alarm or psychotherapy, in addition to desmopressin. Nonresponders were referred to specialized management. The study included 259 children suffering from PNE (92 girls, 167 boys, aged 5-18 years): 42 children were relieved from bedwetting after urotherapy and 136 children had a complete response to desmopressin. Three nonresponders were assigned to specialized management, 61 partial responders had adjuvant treatments, and 17 partial responders had no further treatment. The suggested treatment algorithm resulted in 227 complete responders, 29 partial responders, and 3 nonresponders. The need for preliminary urotherapy is evident. The proposed desmopressin monotherapeutic strategy, incorporating a structured withdrawal program, is more effective than the standard desmopressin treatment module. Applying adjuvant treatment modules improves the complete response rate up to 88%. In partial responders overall efficacy rates are improved further. Nonresponders (1.2%) will be referred to specialized management, but many partial responders will gain improvement sufficient to refrain from invasive procedures.

Adolescent↗

PubMed2004

Lack of ultrastructural detrusor changes following endoscopic injection of botulinum toxin type a in overactive neurogenic bladder.

INTRODUCTION: Endoscopical injections of Botulinum toxin type A into the detrusor muscle are gaining clinical acceptance in the treatment of neurogenic detrusor overactivity. Structural effects of Botulinum toxin type A are only known from studies on striated muscles, where a widespread nerve sprouting occurs temporarily. The aim of this study was to evaluate the ultrastructural effects of Botulinum toxin type A injections on the human detrusor. MATERIAL AND METHODS: 30 detrusor biopsies were obtained from 24 patients with neurogenic detrusor overactivity. Patients were divided into two groups: Group I included 13 biopsies from patients before the first Botulinum toxin type A injection. Group II included 6 biopsies from patients within 3 months after the first injection and 11 biopsies at the time of decreasing efficacy of Botulinum toxin type A. The biopsies were processed by standard procedure for detailed electron microscopic study and evaluated by 2 examiners without prior knowledge of clinical/urodynamic data. RESULTS: No statistically significant detrusor changes have been found concerning muscle cell fascicle structure (p = 0.445), width of intercellular space (p = 0.482) and number/kind of muscle cell junctions (p = 0.443). A median of 70% of intrinsic axon terminals presented with signs of degeneration in group I, a median of 66% in group II (p = 0.840). Out of 309 evaluated axon terminals in both groups, 1 sprouting axon was found in group I, 3 sprouting axons in group II (p = 0.864). Specimen from group I and group II showed only limited collagen deposits within the detrusor. No changes in the ultrastructure of the detrusor have been observed in those biopsies obtained before and after the Botulinum toxin type A injection of the same patient. CONCLUSION: This study verifies our earlier report of severe intrinsic axon degeneration in the detrusor of patients with neurogenic detrusor overactivity. It also shows nearly no structural differences of the detrusor before and after Botulinum toxin type A injections. Contrary to reports of striated muscle, axonal sprouting within the detrusor was very limited after Botulinum toxin type A injections indicating pathophysiologically different reactions to the toxin either between striated muscle and smooth muscle or between different treated diseases.

Adolescent↗

PubMed2004

Over-expression of anti-CD75 reactive proteins on distal and collecting renal tubular epithelial cells in calcium-oxalate stone-forming kidneys in Egypt.

OBJECTIVE: To assess the nature, distribution and expression pattern of CD75, a neuraminidase-sensitive lymphocyte cell surface differentiation antigen, in calcium oxalate (CaOx) stone disease, as cell-surface sialic acid might be involved CaOx crystal binding, and lectin-binding assays suggest that sialic acid in the alpha2,6 position is upregulated in stone-forming kidneys. MATERIALS AND METHODS: Human CaOx stone-forming and normal kidneys (13 each) and primary kidney epithelial cells (CAKI-1, three samples) were analysed. The protein pattern, distribution and expression of CD75 were analysed using Western blotting, immunohistology and semi-quantitative confocal laser scanning microscopy (cLSM). Production was investigated by alpha2,6-sialyltransferase specific reverse transcription-polymerase chain reaction. RESULTS: Western blotting showed one strong band at approximately 43 kDa that reacted with anti-CD75 when renal epithelial and CAKI-1 tumour cell extracts were analysed. However, in renal tissue extracts of CaOx stone formers there were additional bands at 120 and 205 kDa. Image processing after cLSM showed that anti-CD75 reactivity was significantly greater on E-cadherin-positive distal and collecting tubular cells from CaOx stone-forming kidneys, at a mean (sd) intensity of 87 (7), than on those from normal kidneys, at 41 (5) (P = 0.005). CONCLUSION: CD75 expression in human kidney was primarily on the luminal surface of distal tubules and collecting ducts. Whether increased epithelial CD75 expression in CaOx stone disease is a cause or result of the disease remains to be clarified.

Antigens, CD↗

PubMed2004

Functional dissection of Escherichia coli trigger factor: unraveling the function of individual domains.

In Escherichia coli, the ribosome-associated chaperone Trigger Factor (TF) promotes the folding of newly synthesized cytosolic proteins. TF is composed of three domains: an N-terminal domain (N), which mediates ribosome binding; a central domain (P), which has peptidyl-prolyl cis/trans isomerase activity and is involved in substrate binding in vitro; and a C-terminal domain (C) with unknown function. We investigated the contributions of individual domains (N, P, and C) or domain combinations (NP, PC, and NC) to the chaperone activity of TF in vivo and in vitro. All fragments comprising the N domain (N, NP, NC) complemented the synthetic lethality of Deltatig DeltadnaK in cells lacking TF and DnaK, prevented protein aggregation in these cells, and cross-linked to nascent polypeptides in vitro. However, DeltatigDeltadnaK cells expressing the N domain alone grew more slowly and showed less viability than DeltatigDeltadnaK cells synthesizing either NP, NC, or full-length TF, indicating beneficial contributions of the P and C domains to TF's chaperone activity. In an in vitro system with purified components, none of the TF fragments assisted the refolding of denatured d-glyceraldehyde-3-phosphate dehydrogenase in a manner comparable to that of wild-type TF, suggesting that the observed chaperone activity of TF fragments in vivo is dependent on their localization at the ribosome. These results indicate that the N domain, in addition to its function to promote binding to the ribosome, has a chaperone activity per se and is sufficient to substitute for TF in vivo.

Escherichia coli↗

PubMed2003

Intraoperative urodynamics in spinal cord surgery: a study of feasibility.

Intraoperative monitoring (IOM) of bladder function in spinal cord surgery is a challenging task due to vegetative influences, multilevel innervation and numerous supraspinal modulating factors. Despite routine use of urodynamics in neurosurgery for implantation of bladder stimulators or denervation of nerve fibres in spastic reflex bladders, application of IOM in patients with spinal cord tumours or tethered-cord syndrome is not widespread. Combining urodynamics with sphincter electromyography (EMG) in IOM enables identification of bladder efferents responsible for contraction and continence. We monitored four patients with ependymoma of the Cauda equina, one patient with tethered-cord syndrome and two patients with cervical intramedullary tumours. In all patients undergoing operations of the Cauda equina, identification of bladder efferents responsible for detrusor contraction was possible. There was good correlation between preoperative bladder dysfunction, preoperative urodynamics and intraoperative pressure increase by bladder contraction or latency between stimulation and contraction. This method proved unsuitable for intramedullary tumours where no contraction of the bladder could be observed while stimulating the spinal cord. Intraoperative monitoring of urodynamics is an effective tool for identifying bladder efferents in the Cauda equina. Intraoperative conclusions on bladder dysfunction through registration of pressure increase and latency are possible.

Adult↗

PubMed2003

Stone treatment and coagulopathy.

OBJECTIVE: The aim of this retrospective study was to evaluate treatment protocols and results of upper tract stone treatment in patients with clotting disorders. METHODS: In a 6-year period, 6,827 stone interventions (ESWL or endourologic procedures) were performed in 5,739 patients. Thirty-five (0.61%) patients suffered from a variety of systemic clotting disorders or were anti-coagulated. Clotting disorders were corrected by specific therapy prior to any intervention. A total of 76 interventions were performed consisting of ESWL, ureteroscopy (URS), percutaneous nephrolithotomy (PNL), ureteric stenting or percutaneous nephrostomy. RESULTS: All patients became stone-free within 3 months or had clinically insignificant residual fragments. Severe complications were observed in 10/76 (13.1%) interventions. ESWL was successful in 88.9% (16/18) of patients, but associated with a 33.3% (6/18) complication rate; 27.8% (5/18) of patients required auxiliary procedures. URS and PNL were successful in all cases and complications occurred in 0% (0/7) and 33% (1/3) of patients, respectively. Time to complete stone clearance after ESWL was 32.0+/-49.3 days compared with a mean of 19.4+/-28.6 days in a non-coagulopathy control group; no difference was observed for endourologic procedures. Average costs of treatment in patients undergoing ureteroscopy was higher in patients with coagulopathy (4,611 versus 2,342); however, the difference was less pronounced compared with ESWL (6,070 versus 1,731). CONCLUSION: Patients with coagulopathy have a higher rate of complications despite apparently normal clotting parameters during treatment and hospitalisation was prolonged. The efficacy of ESWL was lower in patients with coagulopathy and we currently favour endoscopic procedures for stone removal in this patient group.

Blood Coagulation Disorders↗

PubMed2003

Loss of CD38 correlates with simultaneous up-regulation of human leukocyte antigen-DR in benign prostatic glands, but not in fetal or androgen-ablated glands, and is strongly related to gland atrophy.

OBJECTIVE: To determine whether CD38 loss in benign and malignant prostatic disease is related to human leukocyte antigen (HLA)-DR up-regulation, by assessing the histopathology of the prostate and the effect of androgen deprivation. MATERIALS AND METHODS: Serial sections of frozen fetal (eight), infant (six), normal adult (10), benign hyperplastic (BPH, 24), and primary (10) and hormone-treated (11) carcinomatous human prostatic tissues were analysed by immunohistology for anti-CD38 and HLA-DR antigens. RESULTS: In BPH samples there was a significant correlation between CD38 loss (mean 21% of acini) and HLA-DR up-regulation (mean 20%; P < 0.001). Moreover, 76% of all CD38-negative acini in BPH had HLA-DR up-regulation in the same prostate epithelial cells, predominantly in atrophic and cystic glands, and in cells with retained secretions (74%). In contrast to the uniform expression in normal adult prostate, CD38 was negative or partly expressed in fetal acini (mean 19%) and almost completely negative in acini of the early infant period (mean 0.7%). In contrast to BPH, cancer cells did not selectively up-regulate HLA-DR when CD38 was lost. In patients with cancer treated by androgen deprivation, cancer cells were CD38-negative. CONCLUSIONS: The absence of CD38 and presence of HLA-DR expression in prostatic epithelium is consistent in BPH and tissue surrounding tumour, and strongly related to gland atrophy. This is particularly interesting as HLA-DR triggering can induce apoptosis of cells, whereas CD38 prevents it. A permissive role for androgens to maintain full CD38 expression in epithelial cells is suggested.

ADP-ribosyl Cyclase↗

PubMed2003

Cell-surface matrix proteins and sialic acids in cell-crystal adhesion; the effect of crystal binding on the viability of human CAKI-1 renal epithelial cells.

OBJECTIVE: To investigate the role of sialic acids and cellular matrix proteins as crystal-binding molecules in human calcium-oxalate nephrolithiasis. MATERIALS AND METHODS: The well-defined human renal cancer cell line CAKI-1 was used a standard cell culture system. After enzymatic digestion of various cell surface molecules, the binding of alpha2,6 (Sambucus nigra, SN-) and alpha2,3 (Maackia amurensis, MA)-specific lectins to CAKI-1 cells was analysed. Simultaneously, the effect on adhesion and release of calcium oxalate monohydrate crystals was investigated (eight replicates). The effect of crystal adhesion on cell viability was assessed using Trypan blue exclusion (five replicates). RESULTS: Neuraminidase decreased MA-lectin binding of CAKI-1 cells by 39% (P < 0.05) but elevated SN-lectin binding by 812% (P < 0.05). Simultaneously, crystal binding to CAKI-1 cells was increased by 28% (P > 0.05). Pretreatment with collagenase type I, trypsin and dispase II reduced crystal-binding by 61-74% (P < 0.05) with no effect on sialic acid-specific lectin-binding. However, only collagenase type I and dispase (ratio 4 : 1) were also able to release crystals from their receptor-binding sites (P < 0.05). An increase in the number of cell surface-bound crystals correlated significantly with a decrease in cell viability (P < 0.05). CONCLUSIONS: alpha2,3-linked sialic acids protect cells from crystal-binding. Much greater SN-lectin binding associated with only moderately increased crystal binding argues against alpha2,6-linked sialic acids as a main target structure of crystals. In contrast, collagen type I, type IV and/or fibronectin seem to be potent crystal-binding molecules on human renal epithelial cells, with collagen type I involved in a potential second step of crystal-cell interaction.

Cell Survival↗