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Biomedical subjects

P Wolf

Publications and source records attributed to P Wolf.

At least 145 records · Page 8Linked to original sources
PubMed1998

Antibodies to human adhesion molecules and von Willebrand factor: in vitro cross-species reactivity in the xenotransplantation setting.

Endothelial cell activation is thought to play an important role in xenograft rejection through cell retraction and expression of pro-coagulant and pro-inflammatory factors. Identification of antibodies recognizing porcine endothelial molecules would be useful to study and manipulate the inflammatory response to a xenograft. The aim of this study was to investigate the cross-reactivity of antibodies directed against human adhesion molecules and von Willebrand factor (vWF). Binding of monoclonal antibodies (mAbs) directed against human CD3 1, CD44, CD49, CD54, CD62E, CD102, and CD106 was evaluated on resting and activated endothelial cells from human and pig by flow cytometry. Among 30 antibodies tested, 4 were shown to react with pig cells. Two of them, directed against human CD62E (E-selectin) and rabbit CD106 (VCAM-1) reacted strongly with activated and/or resting pig cells, whereas two others, directed to human CD31 (PECAM) and CD44 (H-CAM), bound weakly to pig cells. In addition, we analyzed the cross-reactivity of five polyclonal or monoclonal antibodies to human or pig vWF with human, baboon, rhesus, pig, and rat vWF. Binding of antibodies was tested by ELISA by using platelet lysates as source of vWF from the different species. Four anti-human or porcine vWF antibodies exhibited a broad reactivity with vWF from all species, whereas one anti-human vWF antibody was specific for primate vWF. In this study, we identified a small number of cross-reacting antibodies that may prove useful to study in vitro and in vivo xenogeneic responses. However, the weak antibody cross-reactivity observed with most porcine molecules points out the necessity of producing species-specific antibodies to study the immune response to xenografts or for use as specific immunosuppressive therapeutic reagents.

Animals↗
PubMed1998

Metabolic capacities in cultured human hepatocytes obtained by a new isolating procedure from non-wedge small liver biopsies.

A new isolating procedure of human hepatocytes has been developed using two-step collagenase digestion by a non-perfusion procedure (NP) of non-wedge liver biopsies. 1. A yield of 2-7 x 10(6) hepatocytes/g liver, 52-95% viability and 13-75% attachment were obtained from liver biopsies weighing 6-60 g, comparable to that obtained when using the classical perfusion procedure (P) to isolate human hepatocytes from wedge liver samples of 50-150 g. 2. In culture, human hepatocytes obtained by NP remained attached to plastic for up to 5 days and displayed the usual morphological characteristics. Their metabolic capacities, assessed by liver-specific albumin and urea synthesis and by CYP-dependent and conjugation pathways, were equivalent to those of human hepatocytes obtained by P. In addition, they responded adequately to specific CYP inducers, demonstrating that they constitute a model in which human drug metabolism and toxicity studies can be performed.

Adult↗
PubMed1998

Possible involvement of Von Willebrand factor in pancreatic graft thrombosis after kidney-pancreas transplantation: a retrospective study.

Early postoperative graft thrombosis remains the second cause of failure in pancreas transplantation. Thus, the aim of this study was to compare retrospectively coagulation and fibrinolysis in type I diabetic recipients of simultaneous kidney pancreas transplants having or not experienced thrombosis of their pancreatic graft. From December 1990 to August 1996, 30 simultaneous kidney pancreas transplants were performed in 30 uremic type I diabetic patients. Acute thrombosis of the pancreatic graft was observed among 6 patients (group A), whereas 24 did not develop thrombosis (group B) although 4 died from other causes. The control groups were composed of kidney transplant (group C) or haemodialysed (group D) non-diabetic patients, type I diabetics with HbA1C < 8% (group E) or > or = 8% (group F) who were not in end-stage renal failure and kidney transplant type I diabetic patients (group G). Beginning at least 6 months after transplantation, we analysed hemostatic factors (fibrinogen, thrombin, and prothrombin times), coagulation inhibitors (proteins C and S), fibrinolysis (plasminogen activator inhibitor) and endothelial cell abnormalities (Von Willebrand factor: VWf). Micro and macrovascular complications were evaluated on a score ranging from 0 to 12. Hemostatic factors, coagulation inhibitors and fibrinolysis were similar in groups A and B whereas VWf differed significantly in group A (3.49 +/- 0.93 IU/ml) as compared to group B (2.04 +/- 0.92 IU/ml) (p < 0.05). VWf was also significantly increased in group A relative to the control groups C, D, E, F, and G. The score of vascular complications was increased in groups A and B and significantly higher in group A (9 +/- 0.81 vs. 6.07 +/- 1.75) (p < 0.01), while a correlation (r = 0.812, p > 0.05) was observed between VWf levels and the severity of vascular complications. These results point out the possible involvement of VWf in the pathogenesis of pancreatic vein thrombosis in kidney-pancreas transplantation.

Adult↗
PubMed1998

Clinical, laboratory, phototest and phototherapy findings in polymorphic light eruptions: a retrospective study of 133 patients.

In the present study, we retrospectively evaluated the clinical, laboratory, phototest and phototherapy findings in 133 patients (109 females and 24 males) with polymorphic light eruption (PLE). The median age of the patients at onset of PLE was 26 years (range, 3-62 years). The median duration of PLE at presentation was 6.5 years (range, 1 week to 25 years). Interestingly, we found two peaks in the distribution curve of the individual latent interval, the time between light exposure and the appearance of skin lesions. The first peak occurred at 1-1.5 hr and the second peak at 24 hrs after light exposure. Six of 33 patients tested had antinuclear antibodies (ANA). However, none of these ANA-positive patients had or developed systemic lupus erythematosus during follow-up. Phototesting revealed that minimal erythema doses for UVA and UVB fell within normal limits in 30 patients tested. Provocative phototesting was positive in 17 of 30 (57%) patients tested. The action spectrum fell within the UVA range in 10 (59%), the UVB range in 4 (23%), and both ranges in 3 (18%) of the 17 cases. Ninety-two patients received preventive phototherapy including broad-band UVB, broad-band UVA, or psoralen and ultraviolet A (PUVA). Follow-up information was available for 79 of these patients: the complete protection rate in the first summer season after therapy was 27% for UVB, 0% for UVA, and 53% for PUVA whereas the overall protection rate (including partial and complete responders) was 83% for UVA, 82% for UVB and 65% for PUVA. In contrast, the patients' histories revealed that the use of a sunscreen with a mean sun protection factor (SPF) of 14 did not prevent skin lesions in 88% of PLE patients.

Adolescent↗
PubMed1997

Disposition of basiliximab, an interleukin-2 receptor monoclonal antibody, in recipients of mismatched cadaver renal allografts.

BACKGROUND: Basiliximab is an interleukin-2 receptor (IL-2R; CD25) chimeric monoclonal antibody for immunoprophylaxis against acute rejection in renal transplantation. Its pharmacokinetics were characterized in a multicenter open-label, prospective dose-escalation study to identify a single-dose regimen providing IL-2R-saturating serum concentrations in the critical first posttransplant month. METHODS: Thirty-two recipients of primary, mismatched cadaver kidneys were enrolled: 20 men and 12 women, who were 47+/-11 years old and weighed 65+/-12 kg. The immunosuppression regimen consisted of steroids and azathioprine from day 0 and cyclosporine from day 10. Basiliximab was infused over 30 min as a single dose preoperatively. RESULTS: Thirty patients were evaluable for basiliximab pharmacokinetics: 24 received 40 mg and 6 received 60 mg. Basiliximab was well tolerated without evidence of cytokine-release syndrome, hypersensitivity reactions, or anti-idiotype antibody response. Peak concentration and area under the concentration curve increased proportionally with dose. Postinfusion concentrations declined in a biphasic manner with a terminal half-life of 6.5+/-2.1 days. Weak, widely dispersed correlations were noted between body weight versus distribution volume (r=0.29) and versus clearance (r=0.45), suggesting no clinical relevance for weight-adjusted dosing. There were no apparent gender-related differences in basiliximab disposition. Previous phase II data indicated that serum concentrations in excess of 0.2 microg/ml are sufficient to saturate IL-2R epitopes on circulating T lymphocytes. Concentrations were above this threshold for 26+/-8 days (range 16 to 46) at the 40-mg dose level and for 32+/-11 days (range 22 to 51) at the 60-mg dose level. CONCLUSIONS: Total basiliximab doses of 40-60 mg were well tolerated, nonimmunogenic, and estimated to provide immunoprophylaxis to cover the first posttransplant month.

Adult↗
PubMed1997

[Which graft for which patient? and when? I. Graft shortage: causes and solutions].

According to the report from the Medical and Scientific Council of Etablissement français des greffes, 2807 organ transplants were performed in France during 1996. After a noticeable decline which started in 1991, transplantation activity has remained stable during the last three years, but does not succeed in satisfying the needs. For instance the average waiting time for a renal graft is longer than two years for certain groups of patients. The origin of this graft shortage is multifactorial, but a certain lack of confidence expressed by family refusal to organ donation is the main reason. Public opinion might have been disturbed some years ago by publications about some dysfunctions in transplantation activity, and by rumors of organ thefts which arise from time to time. Medical information regarding organ harvesting has not always been suitable. Nevertheless, new legal frameworks and new regulations recently established by the public administration, the development of national information campains aimed to health staff and the public, efforts engaged in the use of organ sources other from those harvested from brain dead patients, and the intensification of research, particularly in the field of xenotransplantation are likely to launch once again this magnificient human and scientific adventure, organ transplantation.

Humans↗
PubMed1997

Comparative study of target antigens for primate xenoreactive natural antibodies in pig and rat endothelial cells.

BACKGROUND: A rat-to-primate cardiac xenograft model has been proposed as an alternative to the clinically relevant but more cumbersome pig-to-primate model for assessing the efficacy of strategies aimed at preventing xenograft hyperacute rejection. As in pig xenografts, the rejection of rat hearts was mediated by the binding of xenoreactive natural antibodies (XNA) and complement activation. The present study was conducted to identify target antigens recognized by cynomolgus and rhesus monkey IgM XNA on rat tissues and cells in comparison with pig cells. METHODS: The reactivity of rhesus or cynomolgus serum on pig and rat endothelial cells (ECs) was studied by flow cytometry, ELISA, and complement-dependent cytotoxicity, after removal of primate XNA by perfusion of pig livers, immunoadsorption on a Gal alpha(1,3)Gal affinity column, and enzymatic removal of alpha-galactosyl epitopes from the cell surface. Rat and pig EC extracts were also immunoprecipitated with primate serum and resolved in sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The expression of the Gal alpha(1,3)Gal epitope was analyzed on rat tissues and ECs by immunohistochemistry, flow cytometry, and Western blot, using the isolectin B4 from Griffonia simplicifolia. RESULTS: Removal of primate XNA or of alphaGal epitopes resulted in a decrease in XNA binding to pig and rat cells, leaving a similar degree of residual reactivity in the two species. At least five proteins of 260, 210, 110, 56, and 50 kDa were immunoprecipitated on rat ECs, with molecular weight similar to several proteins identified on pig ECs. These results suggest that primate XNA recognize similar antigens on rat and pig ECs. Rat cells expressed lower levels of the Gal alpha(1,3)Gal epitope than pig cells. A large proportion, but not all, of primate XNA react with this epitope on pig and rat ECs. CONCLUSION: This study suggests that the rat is a valuable species for the evaluation of genetic engineering strategies on the vascular endothelium aimed at preventing hyperacute xenograft rejection.

Animals↗
PubMed1997

Functionality of major histocompatibility complex class II molecules in mice doubly deficient for invariant chain and H-2M complexes.

By combining two previously generated null mutations, Ii degrees and M degrees , we produced mice lacking the invariant chain and H-2M complexes, both required for normal cell-surface expression of major histocompatibility complex class II molecules loaded with the usual diverse array of peptides. As expected, the maturation and transport of class II molecules, their expression at the cell surface, and their capacity to present antigens were quite similar for cells from Ii degrees M degrees double-mutant mice and from animals carrying just the Ii degrees mutation. More surprising were certain features of the CD4(+) T cell repertoire selected in Ii degrees M degrees mice: many fewer cells were selected than in Ii+M degrees animals, and these had been purged of self-reactive specificities, unlike their counterparts in Ii+M degrees animals. These findings suggest (i) that the peptides carried by class II molecules on stromal cells lacking H-2M complexes may almost all derive from invariant chain and (ii) that H-2M complexes edit the peptide array displayed on thymic stromal cells in the absence of invariant chain, showing that it can edit, in vivo, peptides other than CLIP.

Animals↗
PubMed1997

Sequential isologous organ transplantation in inbred rats: pancreaticoduodenal transplants.

A total of 847 inbred Lewis rats of mixed sex were used in this pancreaticoduodenal (Pd) donor aging study. Pd grafts were taken from 9- to 12-month-old donors and transplanted into 3-month-old recipients (thus, the first generation Pd graft, or 1 Pd). After 9 to 12 months, the same Pd grafts were again harvested and transplanted into 3-month-old rats (thus the 2 Pd generation). This cycle was repeated to obtain the 3, 4, and 5 Pd series. Sequential transplantation was able to extend the Pd grafts' mean survival time to 32 months for fourteen 4 Pd grafts, and to 39.2 months for four 5 Pd grafts (the longest lived graft survived for 42 months). The pancreas and duodenal sections of the grafts remained normal throughout the entire study. However, the aortic sections of the grafts (which were harvested to include the superior mesenteric and celiac arteries) all exhibited moderate to massive atherosclerotic changes by the 5 Pd mean survival age of 39.2 months. Such histological changes commenced even before 21 months of Pd graft age in some animals, gradually progressing to dilation of the aorta (and subsequent narrowing of aortic tributaries), as well as formation of an eggshell-like inner membrane shielding the aortic intima, by 42 months. Such atherosclerotic changes precluded transplantations beyond the 5 Pd series.

Age Factors↗
PubMed1997

Cerebellar atrophy decreases the threshold of carbamazepine toxicity in patients with chronic focal epilepsy.

BACKGROUND: Cerebellar atrophy (CA) is a frequent finding in patients with chronic epilepsy. Since gaze-evoked nystagmus, dizziness, and ataxia are some of the typical adverse effects (AEs) of the dose-dependent toxicity of carbamazepine, preexisting CA could possible explain in part the interindividual variation in the tolerance of high serum concentrations of carbamazepine. OBJECTIVE: To determine whether CA reduces the threshold for overdose symptoms with carbamazepine in patients with chronic focal epilepsy in a prospective study. DESIGN: Cohort study. SETTING: A fourth-level epilepsy center to which patients were referred. PATIENTS: Twenty-six consecutive patients with chronic focal epilepsy were prospectively studied while they were receiving high-dose monotherapy with carbamazepine. Patients were slowly titrated to doses at which the first toxic AEs of carbamazepine occurred. The determination of multiple serum levels was carried out, together with an evaluation of toxicity that comprised a standardized neurologic examination, a questionnaire for AEs, and posturography. MAIN OUTCOME MEASURES: Serum concentrations of carbamazepine at the occurrence of the first dose-dependent AEs were related to the presence or absence of CA in magnetic resonance imaging studies as rated by 2 independent and blinded neuroradiologists. RESULTS: In 9 patients (35%), magnetic resonance imaging scans revealed moderate (n = 7) or severe (n = 2) CA. In these patients, gaze-evoked nystagmus (P = .001, log rank test), dizziness (P = .008), and ataxia of stance as measured by posturography (P = .02) occurred at significantly lower serum concentrations of carbamazepine compared with patients without CA. This was also found for the first individually observed AE (P = .03). CONCLUSION: Cerebellar atrophy occurs in a considerable percentage of patients with chronic focal epilepsy and obviously increases the susceptibility for cerebellar AEs of carbamazepine.

Adolescent↗
PubMed1997

Frequency and therapeutic implications of "skip metastases" in the neck from squamous carcinoma of the oral tongue.

BACKGROUND: Supraomohyoid neck dissection is an adequate operation for the elective treatment of the neck for patients with oral cavity cancer. Squamous cell carcinoma of the oral tongue, however, metastasize to clinically negative nodes in 20% to 30% of patients. These nodes usually are located in levels I-III. METHODS: The medical records of 277 previously untreated patients with squamous cell carcinoma of the oral tongue were reviewed between the years 1970 and 1990. All patients had a glossectomy and neck dissection as part of their initial treatment. Patients were evaluated as to the findings in their neck. The following group of patients were included: (1) patients who had level III nodes positive, without disease in levels I and II; (2) patients with disease in level IV; (3) patients with disease in level IIB or IIIB, and; (4) patients who were electively dissected and whose neck did not demonstrate any pathologically involved nodes, but level IV was not included in the dissection and the patient subsequently developed pathologically positive nodes in level IV. RESULTS: Of all patients, 15.8% had either level IV metastasis as the only manifestation of disease in the neck or the level III node was the only node present without disease in level I-II. CONCLUSION: The usual supraomohyoid neck dissection is inadequate for a complete pathologic evaluation of all the nodes at risk for patients with squamous carcinoma of the oral tongue. This may create a dilemma in determining whether postoperative radiotherapy is necessary. Consequently, all patients with squamous cell carcinoma of the oral tongue should have levels I-IV nodes removed if an elective neck dissection is part of their initial therapy.

Carcinoma, Squamous Cell↗
PubMed1997

The genetics of localization-related symptomatic epilepsy: risk of a family history with seizures in patients who have undergone surgery.

A family history of epileptic seizures including febrile convulsions was found in 15 of 103 patients (15%) with localization related epilepsy with partial seizures with and without secondary generalization, who were operated on because of drug resistance. This rate was significantly higher than that of the cumulative incidence in the general population (4%). The localization of the brain damage did not play a role (temporal lobe resection left: 15%, right: 17%, extra-temporal lesion excision: 20%, hemispherectomy: 11%). Various family members were involved. Some patients had more than one relative with seizures. Thus, 21 relatives suffered from seizures. Eleven of them had generalized tonic-clonic seizures (one grand mal on awakening), 7 had febrile convulsions (4 complicated), and in 1 patient the grand mal seizures on awakening were preceded by absences; 1 had generalized tonic-clonic and complex partial seizures; 1 after complicated febrile seizures likewise had complex partial seizures; another mentally retarded patient suffered from generalized tonic-clonic, axial tonic and myoclonic-astatic seizures. The seizure type of 3 remote relatives was not known. The first seizure occurred in 16 family members during childhood, in 3 in adolescence and in only 1 in adulthood (1 unknown). Eight showed mental retardation of slight degree in most. It is interesting that only one-third of the patients with a family history with seizures were seizure-free after the operation; 5 still had seizures, mostly reduced in frequency, 3 had seizures and isolated auras and 2 had only isolated auras. On comparing the findings in patients with and without a family history with seizures, those with family members with epileptic seizures showed a lower rate of an intellectual deficit (7 vs 47%) and brain tumours (13 vs 44%). Our earlier findings with a different group of patients are thus confirmed: that genetics play a role in symptomatic epilepsies.

Adolescent↗