Biomedical subjects

H Zirngibl

Publications and source records attributed to H Zirngibl.

At least 19 recordsLinked to original sources

PubMed2006

Comparison of biomaterials: three meshes and TAPP for inguinal hernia.

BACKGROUND: In laparoscopic hernia repair the use of biocompatible materials is necessary. A prospective, double-blind study was projected to compare three different meshes. METHODS: Ninety male patients with primary inguinal hernia undergoing transabdominal preperitoneal (TAPP) implant procedures were included. Three different types of mesh were tested: a monofile, heavy-weight, rigid mesh (group A), a smooth, heavy-weight variant of polypropylene (group B), and a polyglactin/polypropylene compound mesh (group C). Complications, pain development, inability to work, physical conditions, testicular volume, and blood circulation were documented. RESULTS: Convalescence in group A was slower than in groups B and C: Postoperative values of visual scales for pain development were higher, inability to work was 7.3 days longer, urologic effects were more severe, activities of everyday life were more reduced, and data of the German SF-36 Health Survey Test showed a significant reduction of physical condition (p < 0.05). CONCLUSION: The compound mesh did not create more comfort for the patients than the smooth variant of the heavy-weight polypropylene mesh.

Aged↗

PubMed2006

Comparison of a beta-blocker and an If current inhibitor in rabbits with myocardial infarction.

AIM: We compared protective effects of a ss-adrenoceptor blocker (metoprolol; Met) and a If current (Ivabradine; Iva) in a rabbit model of myocardial infarction. METHODS: Experiments were performed on 44 adult New-Zealand-White (NZW) rabbits. The effects of either metoprolol or ivabradine were assessed 15 min after experimental occlusion of a coronary artery (CAO), 28 days after CAO (drug gavage), and in vitro hearts (Langendorff apparatus). The results were compared with sham and placebo hearts. RESULTS: Metoprolol (0.25 mg/kg) slightly reduced heart rate and left ventricular systolic function. Ivabradine (0.25 mg/kg) reduced heart rate significantly (P<0.05) (18% vs control). Both drugs provided advantages over placebo: mortality was significantly (P<0.01)smaller (6/13 Pla animals died, 2/10 Met animals, and 3/11 Iva animals), left ventricular function was better preserved after 28 days (external power; Pla; Met; Iva=56%; 76%; 74%), and dilatation (BNP) was reduced (P<0.05). In the Pla group, the ST segment was significantly (P<0.05) elevated by 0.35 mV after CAO and exhibited in 50% of the animals Q waves after 28 days, while after ivabradine or metoprolol, ST displacement and Q waves had disappeared. The uneconomic myosin isoenzyme V3 predominated in Met hearts and Iva hearts (V3/V1: 63/37% and 62/38%), while it was further increased in Pla hearts (78/21%). External efficiency was lowest in Pla hearts (1.00+/-0.50 a.u.; P<0.05) and was significantly higher both in Met hearts (4.0+/-1.8 a.u.) and in Iva hearts (3.3+/-1.6 a.u.). CONCLUSIONS: Met and Iva seem suited for the treatment of chronic myocardial infarction.

Adrenergic beta-Antagonists↗

PubMed2003

Comparison of biomaterials in the early postoperative period.

BACKGROUND: Laparoscopic hernia repair necessitates the use of biocompatible materials. A prospective, double-blind study was conducted to compare two different polypropylene meshes. METHODS: The study included 40 men with primary inguinal hernia undergoing transabdominal preperitoneal polypropylene mesh repair. In 20 of these men, a monofile, heavy-weight, rigid mesh was implanted (group A), and in the remaining 20 men, a smooth, heavy-weight variant of polypropylene mesh was implanted (group B). Complications, pain development, inability to work, physical conditions, testicular volume, and blood circulation were documented. RESULTS: Reconvalescence in group A was slower than in group B. In group A, the postoperative values of the visual scales for pain development were higher; inability to work was 7.3 days longer; urologic disorders were worse; activities of everyday life were more reduced; and SF-36 data showed a significant reduction of physical problems ( p < 0.05). CONCLUSIONS: The polypropylene mesh variant seems to be more compatible with the human organism than conventional mesh. Not only the material, but also the structure seems to influence the comfort of the mesh.

Aged↗

PubMed2003

[Urological symptoms after laparoscopic hernia repair. Reduction with a variant of polypropylene mesh].

In the context of a prospective, randomized, controlled double-blind study concerning a reduction of postoperative, urogenital affections after laparoscopic hernia repair using a polypropylene mesh, laparoscopic polypropylene implantation was performed in 40 male patients. Twenty patients received a heavyweight, rigid polypropylene mesh (group A) and the remainder a heavyweight, but softer polypropylene mesh (group B). Questionnaires were used to assess the severity of pain, impairment of sexual life, appearance of urogenital affections, and general condition. On the 3rd postoperative day, testicle blood circulation and testicle volumes were documented by ultrasound, and a congestion of the plexus pampiniformis was excluded by ultrasound with 5 MHz. Starting in the 1st postoperative week, a prevalence of affections such as testicular sensitivity to touch, pain upon ejaculation, and a pulling sensation during urination became apparent in group A. In the 12th postoperative week, 20% in group A still described testicular sensitivity to touch and 10% pain upon ejaculation and a pulling sensation during urination but only 5% in group B. It is essential to reduce urogenital affections after laparoscopic hernia repair by strict indications and appropriately adapted polypropylene meshes.

Aged↗

PubMed2002

[Diagnosis of appendicitis with particular consideration of the acupuncture point Lanwei--a prospective study].

BACKGROUND: In almost all Western industrial nations, appendicitis is the most frequent cause for acute abdomen. Nevertheless, the diagnosis of appendicitis is often difficult, which manifests in highly negative laparotomy rates. In a prospective study we aimed to investigate if palpation of the acupuncture point Lanwei (extra point 22, extra point 33) which is located on the right leg may increase the accuracy in the diagnosis of appendicitis. PATIENTS AND METHODS: Presurgically, the Lanwei point was examined for reproducible tenderness on 116 cooperative nonanesthetized patients admitted to hospital for suspected appendicitis. The results were compared with those of histological diagnosis. The examination of tenderness of the Lanwei sign was performed without knowing the results of other examinations. Additionally, other signs and laboratory parameters for appendicitis were examined using a standardized documentation form. Altogether, 17 presurgical variables, 18 clinical signs, and 3 tests were evaluated. RESULTS: A positive Lanwei sign was documented in 65 cases (56%), whereas 51 patients (44%) had a negative Lanwei sign. 65 of the 116 patients were operated. 59 of those had a histologically proven appendicitis. The sensitivity of the Lanwei sign was 64.4%, specificity ranged at 50%. Rates for positive and negative predictive values were 92.7% and 12.5%, respectively. Odds ratio was estimated as 1.8. When comparing these parameters, the Lanwei sign ranged between the 7th and 10th place of the 22 most important clinical signs for appendicitis. The negative laparotomy rate was 9%, of which 4 of 6 patients had other indications for an operation. The rate of perforation was 15%. CONCLUSION: Compared with many conventional signs for appendicitis as for example Mc Burney, tender Sherren triangle, reduced peristalsis, the diagnostic value of the Lanwei sign is not sufficient. Although a reproducible positive Lanwei sign is a good hint for a true appendicitis, in case of a negative Lanwei sign the probability for an appendicitis may be relatively high. Because of the low negative predictive value, the Lanwei sign is not suitable for reducing negative laparatomy rates. As in many other studies, the one and only indicator for appendicitis which yields high results in all statistical parameters was not detected in this study. In comparison to the statistical parameters of traditional signs for appendicitis, the Lanwei sign cannot be regarded as a good diagnostic parameter for appendicitis.

Acupuncture Points↗

PubMed2002

Perioperative levels of atrial natriuretic peptide and troponin-T in patients with uncomplicated coronary artery surgery.

BACKGROUND HYPOTHESIS: increased ANP levels after uncomplicated coronary artery surgery (CAS) indicate functional reduction. METHODS EXPERIMENTAL DESIGN: prospective, randomized. Preoperative upto the 12 week postoperative. SETTING: Thoracic and Cardiovascular Surgery, University of Düsseldorf. PATIENTS: 15 patients (mean age: 58+/-6.1 years; 13 months, 2 weeks; no myocardial infarction, no congestive heart failure) with 3 vessel disease. INTERVENTIONS: levels of atrial natriuretic peptide (ANP) (pg/ml; radioimmunoassay), Troponin T (TnT) (ng/ml; ELISA test), haemodynamic parameters, ECG monitoring, m-mode echocardiography (Echo). MEASURES: increase of ANP, TnT levels during extracorporeal circulation (ECC), decrease after operation. RESULTS: Maximal increase of ANP from preoperative 90+/-10 (M+/-SEM) pg/ml (p<0.05) up to intraoperative 380+/-38 pg/ml. Ten days postoperative ANP (26+/-33 pg/ml) still threefold increased compared to preoperative level. Increasement of TnT from preoperative 0.02+/-0.01 ng/ml upto intraoperative 3.44+/-0.47 ng/ml. Ten days postoperative TnT concentration normal (0.13+/-0.11 ng/ml). Correlation of ANP and TnT five min after bypass up to 6 hrs postoperative (p<0.05, r =3.4). Increase of left atrial diameter preoperative 42.2+/-1.1 mm up to 46.8+/-1.2 mm (p<0.05) 10 days postoperative. LVEDD, EF changed from preoperative 51.1+/-0.9 mm, 73+/-2% to 54.5+/-1.2 mm, 65+/-4% 10 days postoperative. CONCLUSIONS: Threefold increase of ANP 10 days postoperative and return of TnT levels to normal under consideration of datas of echo show, that ANP is suitable to indicate the meanterm, functional, myocardial reduction. Increased ANP levels, atrial dilatation and dysfunction are important signs of cardial functional reduction after CAS.

Adult↗

PubMed2001

Sympathetic nervous system activity during laparoscopic and needlescopic cholecystectomy.

BACKGROUND: It is difficult to quantify the impact of surgical trauma on patients with conventional measurement techniques. We report our preliminary experience with the determination of sympathetic nervous system activity during laparoscopic and needlescopic cholecystectomy. METHODS: The electroconductivity of representative dermatomes (24 measuring points) was recorded prior, during, and after performing laparoscopic and needlescopic cholecystectomy on 40 consecutive patients according to the method of Nakatani (Ryodoraku). Fifty-five healthy adults served as a control group. RESULTS: Median age in the two groups was 52.4 and 54.1 years, respectively. Prior to the operation and on the 1st postoperative day, sympathetic nervous activity was equal in both groups. In the needlescopic patients, sympathetic activity was lesser at 30 min after the start of the laparoscopic procedure (p <0.05). CONCLUSIONS: The measurement of electroconductivity is a useful noninvasive technique for the evaluation of sympathetic nervous activity. As far as activation of sympathetic nervous system is concerned, the needlescopic technique was found to be superior.

Adult↗

PubMed2001

Evidence for cross-talk between glycoprotein VI and Gi-coupled receptors during collagen-induced platelet aggregation.

Collagen-induced platelet aggregation is a complex process and involves synergistic action of integrins, immunoglobulin (Ig)-like receptors, G-protein-coupled receptors and their ligands, most importantly collagen itself, thromboxane A(2) (TXA(2)), and adenosine diphosphate (ADP). The precise role of each of these receptor systems in the overall processes of activation and aggregation, however, is still poorly defined. Among the collagen receptors expressed on platelets, glycoprotein (GP) VI has been identified to play a crucial role in collagen-induced activation. GPVI is associated with the FcRgamma chain, which serves as the signal transducing unit of the receptor complex. It is well known that clustering of GPVI by highly specific agonists results in platelet activation and irreversible aggregation, but it is unclear whether collagen has the same effect on the receptor. This study shows that platelets from Galphaq-deficient mice, despite their severely impaired response to collagen, normally aggregate on clustering of GPVI, suggesting this not to be the principal mechanism by which collagen activates platelets. On the other hand, dimerization of GPVI by a monoclonal antibody (JAQ1), which by itself did not induce aggregation, provided a sufficient stimulus to potentiate platelet responses to Gi-coupled, but not Gq-coupled, agonists. The combination of JAQ1 and adrenaline or ADP, but not serotonin, resulted in alpha(IIb)beta(3)-dependent aggregation that occurred without intracellular calcium mobilization and shape change in the absence of Galphaq or the P2Y(1) receptor. Together, these results provide evidence for a cross-talk between (dimerized) GPVI and Gi-coupled receptors during collagen-induced platelet aggregation. (Blood. 2001;97:3829-3835)

Animals↗

PubMed2001

Rhodocytin (aggretin) activates platelets lacking alpha(2)beta(1) integrin, glycoprotein VI, and the ligand-binding domain of glycoprotein Ibalpha.

Although alpha(2)beta(1) integrin (glycoprotein Ia/IIa) has been established as a platelet collagen receptor, its role in collagen-induced platelet activation has been controversial. Recently, it has been demonstrated that rhodocytin (also termed aggretin), a snake venom toxin purified from the venom of Calloselasma rhodostoma, induces platelet activation that can be blocked by monoclonal antibodies against alpha(2)beta(1) integrin. This finding suggested that clustering of alpha(2)beta(1) integrin by rhodocytin is sufficient to induce platelet activation and led to the hypothesis that collagen may activate platelets by a similar mechanism. In contrast to these findings, we provided evidence that rhodocytin does not bind to alpha(2)beta(1) integrin. Here we show that the Cre/loxP-mediated loss of beta(1) integrin on mouse platelets has no effect on rhodocytin-induced platelet activation, excluding an essential role of alpha(2)beta(1) integrin in this process. Furthermore, proteolytic cleavage of the 45-kDa N-terminal domain of glycoprotein (GP) Ibalpha either on normal or on beta(1)-null platelets had no significant effect on rhodocytin-induced platelet activation. Moreover, mouse platelets lacking both alpha(2)beta(1) integrin and the activating collagen receptor GPVI responded normally to rhodocytin. Finally, even after additional proteolytic removal of the 45-kDa N-terminal domain of GPIbalpha rhodocytin induced aggregation of these platelets. These results demonstrate that rhodocytin induces platelet activation by mechanisms that are fundamentally different from those induced by collagen.

Animals↗

PubMed2001

Glycoprotein VI but not alpha2beta1 integrin is essential for platelet interaction with collagen.

Platelet adhesion on and activation by components of the extracellular matrix are crucial to arrest post-traumatic bleeding, but can also harm tissue by occluding diseased vessels. Integrin alpha2beta1 is thought to be essential for platelet adhesion to subendothelial collagens, facilitating subsequent interactions with the activating platelet collagen receptor, glycoprotein VI (GPVI). Here we show that Cre/loxP-mediated loss of beta1 integrin on platelets has no significant effect on the bleeding time in mice. Aggregation of beta1-null platelets to native fibrillar collagen is delayed, but not reduced, whereas aggregation to enzymatically digested soluble collagen is abolished. Furthermore, beta1-null platelets adhere to fibrillar, but not soluble collagen under static as well as low (150 s(-1)) and high (1000 s(-1)) shear flow conditions, probably through binding of alphaIIbbeta3 to von Willebrand factor. On the other hand, we show that platelets lacking GPVI can not activate integrins and consequently fail to adhere to and aggregate on fibrillar as well as soluble collagen. These data show that GPVI plays the central role in platelet-collagen interactions by activating different adhesive receptors, including alpha2beta1 integrin, which strengthens adhesion without being essential.

Adenosine Diphosphate↗

PubMed2001

Long-term antithrombotic protection by in vivo depletion of platelet glycoprotein VI in mice.

Coronary artery thrombosis is often initiated by abrupt disruption of the atherosclerotic plaque and activation of platelets on the subendothelial layers in the disrupted plaque. The extracellular matrix protein collagen is the most thrombogenic constituent of the subendothelial layer; therefore, a selective inhibition of the collagen activation pathway in platelets may provide strong antithrombotic protection while preserving other platelet functions. Here we demonstrate that treatment of mice with a monoclonal antibody against the activating platelet collagen receptor glycoprotein VI (GPVI; JAQ1) results in specific depletion of the receptor from circulating platelets and abolished responses of these cells to collagen and collagen-related peptides (CRPs). JAQ1-treated mice were completely protected for at least 2 wk against lethal thromboembolism induced by infusion of a mixture of collagen (0.8 mg/kg) and epinephrine (60 microg/ml). The tail bleeding times in JAQ1-treated mice were only moderately increased compared with control mice probably because the treatment did not affect platelet activation by other agonists such as adenosine diphosphate or phorbol myristate acetate. These results suggest that GPVI might become a target for long-term prophylaxis of ischemic cardiovascular diseases and provide the first evidence that it is possible to specifically deplete an activating glycoprotein receptor from circulating platelets in vivo.

Animals↗

PubMed2001

Evidence for two distinct epitopes within collagen for activation of murine platelets.

It has recently been shown that the monoclonal antibody JAQ1 to murine glycoprotein VI (GPVI) can cause aggregation of mouse platelets upon antibody cross-linking and that collagen-induced platelet aggregation can be inhibited by preincubation of platelets with JAQ1 in the absence of cross-linking (Nieswandt, B., Bergmeier, W., Schulte, V., Rackebrandt, K., Gessner, J. E., and Zirngibl, H. (2000) J. Biol. Chem. 275, 23998-24002). In the present study, we have shown that cross-linking of GPVI by JAQ1 results in tyrosine phosphorylation of the same profile of proteins as that induced by collagen, including the Fc receptor (FcR) gamma-chain, Syk, LAT, SLP-76, and phospholipase C gamma 2. In contrast, platelet aggregation and tyrosine phosphorylation of these proteins were inhibited when mouse platelets were preincubated with JAQ1 in the absence of cross-linking and were subsequently stimulated with a collagen-related peptide (CRP) that is specific for GPVI and low concentrations of collagen. However, at higher concentrations of collagen, but not CRP, aggregation of platelets and tyrosine phosphorylation of the above proteins (except for the adapter LAT) is re-established despite the presence of JAQ1. These observations suggest that a second activatory binding site, which is distinct from the CRP binding site on GPVI on mouse platelets, is occupied in the presence of high concentrations of collagen. Although this could be a second site on GPVI that is activated by a novel motif within the collagen molecule, the absence of LAT phosphorylation in response to collagen in the presence of JAQ1 suggests that this is more likely to be caused by activation of a second receptor that is also coupled to the FcR gamma-chain. The possibility that this response is mediated by a receptor that is not coupled to FcR gamma-chain is excluded on the grounds that aggregation is absent in platelets from FcR gamma-chain-deficient mice.

Amino Acid Motifs↗

PubMed2001

[Jejunum interposition as replacement of the pars descendens duodeni in extensive tubulovillous adenoma].

Reconstruction after partial duodenectomy with resection of the ampulla of Vater is often troublesome. We report the case of a 70-year-old patient with endoscopically non-resectable tubulo-villous adenoma of the descending duodenum including the ampulla of Vater in which subsequent biopsies revealed dysplastic areas. A partial resection of the descending duodenum including the ampulla of Vater was performed. Reconstruction was achieved by the interposition of a jejunal limb in which the ampulla could be reinserted to the posterior wall. The postoperative course was uneventful; a carcinoma was not found within the specimen. In cases of widespread adenomas of the ampulla of Vater, duodenum-preserving resection by interposition of a jejunal limb with reinsertion of the ampulla into the posterior wall may be used as an alternative to Roux-Y reconstruction and to Whipple's procedure.

Adenoma, Villous↗

PubMed2001

[Possibilities and limits of interventional therapy in necrotizing pancreatitis].

We present a new technique for minimal invasive radiological assisted necrosectomy (MIRAN) for infected necrosis in acute pancreatitis. We describe how to place volumic catheters for fragmentation and extraction of necrotic material. In addition a new technique is described for minimal invasive occlusion of selected pancreas tail to avoid fistulas. In 26 patients with infected necrosis of the pancreatic region, 12 patients (46.2%) could be healed by MIRAN alone. 5 patients (19.2%) could be satisfactory treated with a combination of MIRAN and operative necrosectomy. 9 patients (34.6%) died, 5 of them postoperatively. In 7 cases death followed multiple organ failure/dysfunction syndrome. 12 (71%) of 17 patients with the aim of curative treatment could be satisfactory treated with MIRAN. 2 other patients (12%) received additional surgery, 3 patients died (17%), 2 of them without any other treatment. The advantages of MIRAN are reduced trauma, general anaesthesia is not necessary, no difficult surgical preparation is necessary, no limits for additional therapy, reduced damage of neighbouring organs and vital pancreatic tissue as well as avoiding splenectomy.

Cause of Death↗

PubMed2001

Laparoscopic intraperitoneal onlay polytetrafluoroethylene mesh repair (IPOM) for inguinal hernia during spinal anesthesia in patients with severe medical conditions.

In patients with severe pulmonary disease, laparoscopic techniques are not advised. The authors report their preliminary experience with laparoscopic intraperitoneal onlay polytetrafluoroethylene mesh repair for inguinal hernia during spinal anesthesia in patients with chronic obstructive pulmonary disease. Spinal anesthesia was performed using hyperbaric bupivacaine (3-3.5 mL) injected at L2-L3. If necessary, additive opioid therapy was administered. Under low-pressure pneumoperitoneum (10 mm Hg), polytetrafluoroethylene mesh was stapled securely on the posterior inguinal wall to spare epigastric and iliac vessels. Fifteen patients underwent surgery. Median age was 62 years. All patients were classified American Society of Anesthesiologists physical status III/IV. Mean forced expiratory volume in the first second was 1.1 L/s. Median operating time was 20 minutes. Postoperative recovery was uneventful for all patients. The average duration of hospital stay was 1.5 days. Seroma or hematoma was not noted. Six-month follow-up did not show recurrence or infection. This technique is an effective method of repair of inguinal hernia in patients with severe chronic obstructive pulmonary disease, and it provides a maximum of comfort.

Aged↗

PubMed2001

[Laparoscopic colon surgery].

We review our experience in laparoscopic colorectal surgery, with indications, technical aspects and results. Between 1992 and 31/12/2000, we performed 113 laparoscopic or laparoscopically assisted colorectal operations. Of 79 malignant cases, 37 operations were oncologically radical and therapeutic, 42 were palliative. During the immediate postoperative period two deaths occurred (2.8%), the causes of death were not related to surgery. Port site metastasis developed in one patient (1.4%). Postoperative complications developed in 18 patients (14.5%). Only one patient required conversion to laparotomy. We emphasize the importance of hand assisted laparoscopic surgery (HALS) in laparoscopic colorectal surgery, because it can increase the number of laparoscopic colorectal operations. Based on our results and experience, we recommend the routine use of laparoscopic technique in colorectal surgery.

Colitis, Ulcerative↗

PubMed2000

Identification of critical antigen-specific mechanisms in the development of immune thrombocytopenic purpura in mice.

The pathogenic effects of antiplatelet antibodies were investigated in mice. Monoclonal antibodies (mAbs) of different immunoglobulin G subclass directed against mouse GPIIbIIIa, GPIIIa, GPIbalpha, GPIb-IX, GPV, and CD31 were generated and characterized biochemically. MAbs against GPIb-IX, GPV, CD31, and linear epitopes on GPIIIa had mild and transient effects on platelet counts and induced no spontaneous bleeding. Anti-GPIbalpha mAbs induced profound irreversible thrombocytopenia (< 3% of normal) by Fc-independent mechanisms but only had minor effects on hematocrits. In contrast, injection of intact mAbs, but not F(ab)(2) fragments, against conformational epitopes on GPIIbIIIa, induced irreversible thrombocytopenia, acute systemic reactions, hypothermia, decreased hematocrits, and a paradoxical loss of surface GPIIbIIIa on platelets in vivo, the latter suggesting the formation of platelet-derived microparticles. Blockage of platelet-activating factor receptors inhibited the acute reactions, but not thrombocytopenia, loss of GPIIbIIIa, and decreases in hematocrits. Repeated injections of low doses of anti-GPIIbIIIa antibodies resulted in profound thrombocytopenia and bleeding, whereas no acute systemic reactions were observed. These data strongly suggest that the identity of the target antigen recognized by antiplatelet antibodies determines the mechanisms of platelet destruction and the severity of bleeding in mice, the latter depending on previously unrecognized anti-GPIIbIIIa-specific inflammatory mechanisms.

Animals↗

PubMed2000

Expression and function of the mouse collagen receptor glycoprotein VI is strictly dependent on its association with the FcRgamma chain.

Platelet glycoprotein (GP) VI has been proposed as the major collagen receptor for activation of human platelets. Human GPVI belongs to the immunoglobulin superfamily and is noncovalently associated with the FcRgamma chain that is involved in signaling through the receptor. In mice, similar mechanisms seem to exist as platelets from FcRgamma chain-deficient mice do not aggregate in response to collagen. However, the activating collagen receptor on mouse platelets has not been definitively identified. In the current study we examined the function and in vivo expression of GPVI in control and FcRgamma chain-deficient mice with the first monoclonal antibody against GPVI (JAQ1). On wild type platelets, JAQ1 inhibited platelet aggregation induced by collagen but not PMA or thrombin. Cross-linking of bound JAQ1, on the other hand, induced aggregation of wild type but not FcRgamma chain-deficient platelets. JAQ1 stained platelets and megakaryocytes from wild type but not FcRgamma chain-deficient mice. Furthermore, JAQ1 recognized GPVI (approximately 60 kDa) in immunoprecipitation and Western blot experiments with wild type but not FcRgamma chain-deficient platelets. These results strongly suggest that GPVI is the collagen receptor responsible for platelet activation in mice and demonstrate that the association with the FcRgamma chain is critical for its expression and function.

Animals↗