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Biomedical subjects

M Simon

Publications and source records attributed to M Simon.

At least 127 records · Page 7Linked to original sources
PubMed1998

Idiopathic recurrent palmoplantar hidradenitis in children. Report of 22 cases.

BACKGROUND: Idiopathic recurrent palmoplantar hidradenitis (IRPH) is characterized by tender erythematous plaques and nodules on the soles and, less often, the palms of young patients. To date, 10 cases of IRPH have been documented in the literature. OBSERVATIONS: We describe 22 pediatric patients with characteristic cutaneous and histologic findings of IRPH. Their mean age was 6 years (age range, 1.5-15 years). The onset of the disease clustered in 2 peaks, in autumn and spring. All patients had complete resolution of their lesions within 3 weeks, in 16 cases without any treatment. Ten of the 22 patients experienced more than 1 episode of IRPH. CONCLUSIONS: Our study represents the largest number of cases of IRPH collected to date. Based on our data, the clinical picture is so characteristic that a histopathologic examination may not be necessary in every case. We suggest that there is a seasonality in the occurrence of this always benign and limited disease.

Administration, Cutaneous↗
PubMed1998

[Dose-dependent pellagroid skin reaction caused by carbamazepine].

A 11-year-old girl suffering from grand mal epilepsy underwent antiepileptic therapy with carbamazepine (600 mg/daily). Two weeks after increasing the dose (900 mg/day) she suddenly developed relatively sharply limited, sunburn-like brown reddish macular lesions with central scaling and partly hyperkeratotic areas on the hands, feet, face, knees, gluteal and axillar regions. Otherwise no health disorders were found; in particular no neurological or gastrointestinal symptoms occurred. After reduction of the doses (450 mg/day) these skin lesions faded away. With exception of elevated serum levels of carbamazepine, nicotinamide and vitamin B6, all blood tests were in normal range. Interactions of carbamazepine with the vitamin B6- nicotinamide metabolism are the reason for these previously undescribed cutaneous side effects in connection with carbamazepine therapy. The present case demonstrates a toxic, non-allergic reaction during carbamazepine treatment with pellagroid skin symptoms.

Anticonvulsants↗
PubMed1998

Cultured human sole-derived keratinocyte grafts re-express site-specific differentiation after transplantation.

Cultured epithelial autografts (CEA) derived from sole skin were transplanted to full-thickness wounds excised to muscle fascia over a variety of diverse body sites in 12 pediatric patients treated for acute burns or giant congenital nevi. The skin regenerated from the grafts was biopsied from 7 days to 6 years after grafting. The resultant epidermal phenotype was analyzed histologically and by immunohistochemical localization of keratin 9 (K9) as objective evidence of sole-type site-specific differentiation. Expression of K9 was also verified by one-dimensional gel electrophoresis of epidermal cytoskeletal extracts and K9 immunoblot analysis. Grafts prepared from epidermis of axilla; groin or foreskin and transplanted to wounds of comparable depth in an identical manner in the same patients served as controls of postgrafting differentiation. Biopsies of sole skin from amputation specimens from patients of comparable age served as normal positive controls, and biopsies of nonsole skin from patients of comparable age served as normal negative controls. As early as 2 weeks postgrafting, the histologic appearance of sole-derived CEA differed substantively from that of axilla- or groin-derived CEA controls and displayed a phenotype characteristic of sole skin with a thick compact stratum corneum, a thick stratum granulosum, and a distinct stratum lucidum. In sole-derived grafts rete ridges regenerated within 2 months postgrafting, whereas nonsole-derived grafts required 4-6 months for rete ridge regeneration. Once acquired, the sole skin phenotype was maintained long-term by all sole-derived CEA. In vitro, sole-derived keratinocytes synthesized little, if any, K9. However, within 7 days after grafting, K9 synthesis by multiple suprabasal keratinocytes was seen within the epidermis regenerated from sole-derived CEA. Protein of K9 appeared progressively more diffuse throughout the suprabasal layers, attaining a confluent pattern of expression comparable to normal controls of sole skin by 6 to 12 months postgrafting, and the confluent pattern of suprabasal K9 synthesis was maintained long-term. The results demonstrate that site-specific differentiation is an intrinsic property of postnatal human keratinocytes and can be expressed and maintained in a permissive environment in the absence of dermal tissue.

Adolescent↗
PubMed1998

Dermal fibroblasts actively metabolize retinoic acid but not retinol.

The accessibility of plasma retinol and retinoic acid to the epidermis may be influenced by the number and metabolic capacity of fibroblasts in papillary dermis. The metabolism of retinol-binding protein-bound all-trans-retinol, and albumin-bound all-trans-retinoic acid, by fibroblasts cultured on plastic dishes or in type I collagen gels, was examined. There were no significant differences in the metabolism of either retinoid by fibroblasts as a function of culture condition. There were large differences between retinoids, however. Retinoic acid was rapidly taken up and metabolized to unidentified polar metabolites that were released to the medium. Metabolic capacity was not saturated up to a medium retinoic acid concentration of 1 microM, and was induced further by prior exposure to retinoic acid. In contrast, retinol, although readily taken up, was not metabolized, i.e., neither retinoic acid nor retinyl ester was formed. By immunohistochemistry, the average number of fibroblasts in a 100 microm thickness of papillary dermis was estimated to be 1 x 10(6) cells per cm2. Utilizing this value, the capacity of dermal fibroblasts to metabolize retinoic acid based on fibroblast abundance in the dermis was calculated. The results suggest that fibroblasts could limit delivery of plasma retinoic acid but not retinol to the epidermis on the basis of their metabolic capacity and abundance in the dermis.

Cells, Cultured↗
PubMed1998

Shiga toxin 1 elicits diverse biologic responses in mesangial cells.

BACKGROUND: Shiga toxin 1 (Stx1) is a causative agent in hemolytic uremic syndrome (HUS). Its receptor, the glycosphingolipid globotriaosylceramide (Gb3), is expressed on cultured human endothelial and mesangial cells. Mesangial cell injury in HUS ranges from mild cellular edema to severe mesangiolysis and eventual glomerulosclerosis. We hypothesized that, in addition to endothelial cells, mesangial cells are targets of Stx1. METHODS: Human mesangial cells were exposed to Stx1. Protein synthesis was measured using [35S]-methionine/cysteine. Cell viability was measured as the lysosomal uptake of Neutral Red. Monocyte chemotactic peptide (MCP-1) mRNA and protein were analyzed by Northern blotting and ELISA. RESULTS: Stx1 (0.25 to 2500 ng/ml) resulted in a dose-dependent inhibition of protein synthesis. This effect of Stx1 was potentiated by preincubation of the cells with interleukin-1alpha (IL-1alpha; 2 ng/ml) or tumor necrosis-alpha (TNF-alpha; 500 U/ml). Stx1 had little effect on mesangial cell viability during the first 24 hours of exposure to Stx1. However, prolonged incubation with Stx1 for 48 and 72 hours resulted in a 68% and 80% decrease in cell-viability, respectively. Stx1 elicited a dose and time dependent increase in the levels of MCP-1 mRNA, an effect that was potentiated by preincubation with IL-1alpha. CONCLUSION: These data indicate that mesangial cells are susceptible to the effects of Stx1 in vitro. Stx1 exerts a spectrum of biologic effects on mesangial cells ranging from activation of chemokine genes to a lethal toxic injury. Immunoinflammatory cytokines potentiate the effects of Stx1. Thus, glomerular pathology in HUS may also result from a direct effect of Stx1 on mesangial cells.

Bacterial Toxins↗
PubMed1998

Effects of vascular endothelial growth factor (VEGF)/vascular permeability factor (VPF) on haemodynamics and permselectivity of the isolated perfused rat kidney.

BACKGROUND: Vascular endothelial growth factor (VEGF) or vascular permeability factor (VPF) is a selective mitogen for endothelial cells; it increases microvascular permeability and has been shown to relax isolated canine coronary arteries by an endothelium-dependent mechanism. In many tissues VEGF/VPF is expressed after an appropriate stimulus, mostly hypoxia. In the kidney VEGF/VPF is constitutively expressed in glomerular podocytes and epithelia of collecting duct. Glomerular and peritubular capillary endothelia also constitutively express specific VEGF receptors. The in vivo function of renal VEGF/VPF is unknown. METHOD: In the present study the effects of human recombinant VEGF165 on renal haemodynamics and glomerular permselectivity was investigated in the isolated perfused kidney of the rat. RESULTS: In kidneys preconstricted by noradrenaline (NA 1.5 x 10(-7) mol/l) VEGF/VPF (155 pmol/l) caused an almost complete return of renal perfusion flow rate to pre-NA values (before NA 113 +/- 4%, after NA 100%, 15 min with VEGF/VPF 111 +/- 4%). Shortly after VEGF/VPF administration VEGF/VPF-induced relaxation commenced, and became significant after 2 min (15 min with VEGF/VPF vs without VEGF/VPF 111 +/- 4% vs 103 +/- 2%; P<0.05). In the presence of the NO-synthase inhibitor N(W)-nitro-L-arginine (L-NNA; 5 x 10(-5) mol/l) VEGF/VPF caused only small, transient relaxations (before NNA 109 +/- 5%, after NNA 100%, 15 min with VEGF 95 +/- 2%). The cyclooxygenase inhibitor diclofenac failed to inhibit the relaxing activity of VEGF/VPF (before NA 119 +/- 4%, after NA + diclofenac 100%, 15 min with VEGF/VPF 123 +/- 5%). VEGF demonstrated no significant increase in renal protein excretion rate (after NA pretreatment (= 100%): 12.5 min with VEGF/VPF vs without VEGF/VPF: 119 +/- 10% vs 132 +/- 11%, n.s.) (after NNA pretreatment (= 100%) 12.5 min with VEGF/VPF vs without VEGF/VPF 94 +/- 5% vs 96 +/- 4%; n.s.) or clearance quotient of albumin. Glomerular filtration rate was not influenced by VEGF/VPF in kidneys pretreated with NA (before NA 105 +/- 5%, after NA 100%, 12.5 min with VEGF/VPF 94 +/- 2%) or with NNA (before NNA 107 +/- 6%, after NNA 100%, 12.5 min with VEGF/VPF 96 +/- 2%). Fractional glucose and fractional sodium excretion showed flow-dependent changes. CONCLUSION: VEGF/VPF can contribute to the relaxing capacity of the renal vasculature. This relaxation is partly mediated by the NO/endothelium-derived relaxing factor (EDRF) pathway. In the isolated perfused rat kidney the glomerular permeability for albumin is not affected by VEGF/VPF.

Animals↗
PubMed1998

Mutation of the Lck-binding motif of Tip enhances lymphoid cell activation by herpesvirus saimiri.

The proline-rich SH3-binding (SH3B) motif of the tyrosine kinase-interacting protein (Tip) of herpesvirus saimiri (HVS) is required for binding to the cellular Src family kinase Lck. We constructed a mutant form of HVS in which prolines in the SH3B motif of Tip were altered to alanines. This mutant form of Tip was incapable of binding to Lck. The mutant virus, HVS/Tip mSH3B, retained its ability to immortalize common marmoset lymphocytes in culture. In fact, common marmoset lymphocytes immortalized by the HVS/Tip mSH3B mutant displayed increased expression of HLA-DR lymphocyte activation marker, an altered pattern of tyrosine phosphorylation, increased expression of the tyrosine kinase Lyn, and a shift in electrophoretic mobility of Lck compared to cells immortalized by wild-type HVS. Experimental infection of common marmosets resulted in fulminant lymphoma with both HVS/Tip mSH3B and wild-type HVS. However, HVS/Tip mSH3B produced greater infiltration of affected organs by proliferating lymphoid cells compared to wild-type HVS. These results demonstrate that Tip binding to Lck is not necessary for transformation and that abrogation of Tip binding to Lck alters the characteristics of transformed cells and the severity of the pathologic lesions.

Animals↗
PubMed1998

Receptors of vascular endothelial growth factor/vascular permeability factor (VEGF/VPF) in fetal and adult human kidney: localization and [125I]VEGF binding sites.

Vascular endothelial growth factor (VEGF) has an important function in renal vascular ontogenesis and is constitutively expressed in podocytes of the adult kidney. The ability of VEGF to be chemotactic for monocytes and to increase the activity of collagenase and plasminogen activator may have implications for renal development and renal disease. In humans, the cellular actions of VEGF depend on binding to two specific receptors: Flt-1 and KDR. The aims of this study were: (1) to localize VEGF receptor proteins in human renal ontogenesis; (2) to quantify VEGF binding in human fetal and adult kidney; and (3) to dissect the binding into its two known components: the KDR and Flt-1 receptors. The latter aim was achieved by competitive binding of VEGF and placenta growth factor-2, which only binds to Flt-1. Quantification of 125I-VEGF binding sites was performed by autoradiography and computerized densitometry. By double-label immunohistochemistry, VEGF receptor proteins were localized solely to endothelial cells of preglomerular vessels, glomeruli, and postglomerular vessels. In developing glomeruli, VEGF receptor protein appeared as soon as endothelial cells were positive for von Willebrand factor. Specific 125I-VEGF binding could be localized to renal arteries and veins, glomeruli, and the tubulointerstitial capillary network in different developmental stages. Affinity (Kd) of adult (aK) and fetal (fK) kidneys was: Kd: glomeruli 38.6 +/- 11.2 (aK, n = 5), 36.3 +/- 7.1 (fK, n = 5); cortical tubulointerstitium 19.4 +/- 2.6 (aK, n = 5), 11.6 +/- 7.0 (fK, n = 5) pmol. Placenta growth factor-2 displaced VEGF binding in all renal structures by approximately 60%. VEGF receptor proteins thus were found only in renal endothelial cells. A coexpression of both VEGF binding sites could be shown, with Flt-1 demonstrating the most abundant VEGF receptor binding sites in the kidney. These studies support the hypothesis of a function for VEGF in adult kidney that is independent of angiogenesis.

Adult↗
PubMed1998

An international dermatological image atlas on the WWW: practical use for undergraduate and continuing medical education, patient education and epidemiological research.

We describe the development of an image database DOIA (Dermatological OnlIne Atlas) and present several spin-off projects using images of the atlas, e.g. student education using the atlas including results of an questionnaire evaluating computer-literacy, prerequisites and interests of students for using computers and the World-Wide-Web (WWW), a patient information system and an experiment to collect epidemiological data from patients with dermatological diseases via WWW. The database, available on the WWW at http:@www.derma.med.uni-erlangen.de, contains about 3,000 clinical images covering more than 540 dermatological diagnoses. It is designed for worldwide use; international submissions are encouraged. One aim of the project is to compile an international reference for dermatological images, containing images of high educational quality and also covering conditions on different skin types and rare diagnoses which are not commonly illustrated in ordinary textbooks. All images were originally mapped to the Erlanger Diagnosis Code, which is a proprietary modified ICD-9 key, later also to the UMLS (Unified Medical Language System). In addition, images are described with keys for the location, physical attributes of the location and clinical and histopathological features of the lesion. In order to facilitate the integration of the atlas into other web-based medical resources and to allow easy access to additional information, the Erlanger Diagnosis Code was mapped to the CUIs (unique concept identifiers) of the UMLS Metathesaurus. One purpose of the UMLS is to allow conversion of terms from one controlled medical vocabulary to another, thus, mapping of our diagnosis code to the UMLS CUIs allows simultaneous search for a given diagnosis in a number of other databases and also access to our image database from other databases. Mapping was successful for 619 out of 1383 dermatological diagnosis terms. For images with these diagnoses we are able to provide a hyperlink to other databases available on the Internet, such as MEDLINE, PDQ and OMIM, with automatic retrieval using the preferred vocabulary of the respective database. By grouping all diagnoses into sets with similar morphologies we further integrated a differential diagnosis mode. In order to educate patients via the Internet, a separate patient information system has been developed, using images of the electronic atlas. As an experiment to explore the feasibility of the Internet to gather epidemiological data from patients, users are asked to complete an electronic questionnaire covering signs for atopy. We conclude that an online image atlas has multiple educational, clinical and research applications.

Computer-Assisted Instruction↗
PubMed1998

Automated high-resolution polymerase chain reaction fragment analysis: a method for detecting T-cell receptor gamma-chain gene rearrangements in lymphoproliferative diseases.

Southern blot analysis and the polymerase chain reaction (PCR) are powerful tools for detecting clonal antigen receptor gene rearrangements. However, a number of limitations restrict the predictive value of the results obtained by these techniques as they are commonly used. We describe a new method, automated high-resolution PCR fragment analysis, that can partially overcome many of the limitations of analyzing the T-cell receptor (TCR) gamma-chain gene. Analysis of TCR-gamma is performed using PCR with four sets of primers, previously described by others, specific for all variable (V) and joining (J) regions of the TCR gamma-chain gene. In addition, the four V region primers are 5' end-labeled with a fluorescent compound, 5-carboxyfluorescein. After amplification, the labeled PCR products are separated with an automated sequencing system, ABI 373 (Applied Biosystems, Weiterstadt, Germany). With the help of the Gene-Scan software ABI 672 (Applied Biosystems) and fluorescent-labeled DNA length markers, the exact size of each peak can be displayed and analyzed. The resolution of this method allows separation of PCR products differing in length by as little as 1 bp. Semiquantitative estimation of specific clones also can be performed. Infiltrate-specific gene rearrangement patterns can be identified and recognized in different tissue specimens at the time of diagnosis or in subsequent biopsy specimens. We conclude that automated high-resolution PCR fragment analysis allows more accurate and convenient analysis of the TCR gamma-chain gene.

Automation↗
PubMed1998

Clinical laboratory test menu changes in the Pacific Northwest: 1994 to 1996.

Laboratory testing services are presently undergoing dynamic changes in response to a wide range of external factors. Government regulations, reimbursement, and managed care are only a few of the influences affecting the availability of testing services and on-site testing capabilities in hospital, independent, and physician office laboratories. Medical practice changes, marketplace influences, test technologies, and costs also play a role in determining where testing is being performed. To better understand the factors influencing clinical laboratory test volumes and menus and to identify on-site testing deemed essential in physician office laboratories, we gathered information from a network of clinical laboratories in the Pacific Northwest. Questionnaires were sent to 257 Laboratory Medicine Sentinel Monitoring Network participants in March 1996. In the past 2 years, changes in on-site test volumes and test menus have been primarily due to medical practice changes and marketplace influences. When laboratories had a decrease in test volumes or test menu choices, the size of the patient workload and the volumes of test orders have had the greatest impact. Laboratory regulations and managed care contracts have played a role in shifting on-site testing to outside sources; however, these factors did not appear to be primary influences. Only 5% of physician office laboratories identified tests that they believed were essential for optimal patient care but did not perform on-site.

Alaska↗
PubMed1998

Immunoblotting detection of autoantibodies to human epidermis filaggrin: a new diagnostic test for rheumatoid arthritis.

OBJECTIVE: We previously reported that so-called antikeratin antibodies (AKA) and antiperinuclear factor (APF) recognize epitope(s) present on human epidermal filaggrin. In the present study, we developed a new diagnostic test for rheumatoid arthritis (RA) based on detection of antifilaggrin autoantibodies (AFA) by immunoblotting. METHODS: We tested 670 serum samples, including 190 RA. AFA titers were estimated by immunoblotting on filaggrin enriched human epidermis extracts, and AKA titers by indirect immunofluorescence (IIF) on rat esophagus epithelium. Diagnostic values of the tests were compared. RESULTS: Each test resulted in diagnosis of more than 40% of RA samples, with a specificity of 0.99. Although the tests were strongly correlated, their association allowed the diagnosis of more than 60% of RA samples, with the same specificity. CONCLUSION: Immunoblot detection of AFA, a simple and standardizable test, may be an alternative or complement to conventional IIF detection of AKA.

Adolescent↗
PubMed1998

The spontaneous aortocaval fistula: a complication of the abdominal aortic aneurysm. Case report and review of the literature.

An aortocaval fistula is a rare complication of the abdominal aortic aneurysm: early diagnosis and appropriate surgery improve survival. We report the case of a patient presenting with abdominal pain and oedema of both lower limbs secondary to an aortocaval fistula. CT-scan confirmed the diagnosis and successful surgery was performed in the emergency room. Immediate haemostasis on the inferior vena cava is easier when preoperative diagnosis of the fistula has been made.

Aortic Aneurysm, Abdominal↗
PubMed1997

Mycophenolate mofetil decreases rejection in simultaneous pancreas-kidney transplantation when combined with tacrolimus or cyclosporine.

BACKGROUND: Historically, the acute rejection rates in simultaneous pancreas-kidney (SPK) recipients have been extremely high (50-80%), with many second and third rejection episodes despite the use of quadruple immunosuppression (antibody induction and cyclosporine [CsA]-azathioprine [AZA]-based maintenance immunosuppression). Although this acute rejection has rarely led to graft loss, it has been a great cause of morbidity and of significantly increased cost. In an attempt to decrease the acute rejection rate and related morbidity in SPK transplant recipients, we compared two "state-of-the-art" immunosuppression regimens in a prospective, randomized, single-center study. METHODS: Patients who received SPK transplants were randomized to receive either tacrolimus (TAC) and mycophenolate mofetil (MMF, n=18) or CsA (Neoral formulation) and MMF (n=18). All patients received OKT3 induction and prednisone, which was tapered to 5 mg/day by 6 months after transplantation. All rejection episodes were biopsy proven. In addition, metabolic control (HgbA1C, hypertension, serum cholesterol), drug toxicity, and infection also were measured. Data were compared with that of a historical group (n=18) who received conventional CsA (Sandimmune formulation) and AZA-based immunosuppression. RESULTS: The incidence of biopsy-proven acute rejection was 11% in both the TAC-MMF and CsA-MMF groups with only two patients in each group experiencing a rejection episode. This rejection rate was significantly decreased from that of the CsA-AZA historical group (77%, P<0.01). There were no significant differences in infection rates, including cytomegalovirus, or in metabolic control (HgbA1C, hypertension, and cholesterol levels). All patients remained on their initial immunosuppression regimen for the first 3 months after transplantation. Between 3 and 6 months after transplantation, three patients were switched from TAC to CsA for recurrent migraine headaches, posttransplant diabetes, and chronic cytomegalovirus infection. Two patients in the CsA-MMF group died of nonimmunologic causes (aspiration pneumonia and arrhythmia) between 3 and 6 months after transplantation. CONCLUSIONS: The data from this study show that MMF treatment significantly decreases the incidence of biopsy-proven acute rejection in SPK transplant recipients compared with AZA-treated historical controls. In addition, we conclude that TAC and CsA (Neoral), when combined with MMF, yield similar, low acute rejection rates with similar graft function and metabolic control.

Adult↗
PubMed1997

Characterization and purification of human corneodesmosin, an epidermal basic glycoprotein associated with corneocyte-specific modified desmosomes.

Using monoclonal antibodies, we identified a new protein in mammalian epidermis, which we called corneodesmosin. It is located in the extracellular part of the modified desmosomes in the cornified layer of the tissue, and its proteolysis (from 52-56 to 33 kDa) is thought to be a major prerequisite of desquamation. We have now further characterized human corneodesmosin. Proteolysis of purified cornified cell envelopes produced immunoreactive fragments, confirming the covalent linkage of the protein to these structures. Sequential extraction of epidermal proteins indicated that the 52-56-kDa precursor form of the protein exists in two distinct pools, one extracted with a nondenaturing hypotonic buffer, and the other with urea. Two-dimensional gel analysis and reactivity with phosphoserine-specific antibodies showed that it is a basic phosphoprotein. Deglycosylation experiments, reactivity with lectins, and chromatography on concanavalin A-Sepharose indicated that corneodesmosin is N-glycosylated. Partial sequences, 10 and 15 amino acids long, of the purified 52-56-kDa corneodesmosin showed identity with sequences predicted from a previously cloned gene, proved to be expressed in the epidermis and designated S. This indicates that corneodesmosin is probably encoded by the S gene, the function of which was unknown until now. A model of corneodesmosin maturation during cornification is proposed.

Amino Acid Sequence↗
PubMed1997

The Ca2+-dependent binding of calmodulin to an N-terminal motif of the heterotrimeric G protein beta subunit.

Ca2+ ion concentration changes are critical events in signal transduction. The Ca2+-dependent interactions of calmodulin (CaM) with its target proteins play an essential role in a variety of cellular functions. In this study, we investigated the interactions of G protein betagamma subunits with CaM. We found that CaM binds to known betagamma subunits and these interactions are Ca2+-dependent. The CaM-binding domain in Gbetagamma subunits is identified as Gbeta residues 40-63. Peptides derived from the Gbeta protein not only produce a Ca2+-dependent gel mobility shifting of CaM but also inhibit the CaM-mediated activation of CaM kinase II. Specific amino acid residues critical for the binding of Gbetagamma to CaM were also identified. We then investigated the potential function of these interactions and showed that binding of CaM to Gbetagamma inhibits the pertussis toxin-catalyzed ADP-ribosylation of Galphao subunits, presumably by inhibiting heterotrimer formation. Furthermore, we demonstrated that interaction with CaM has little effect on the activation of phospholipase C-beta2 by Gbetagamma subunits, supporting the notion that different domains of Gbetagamma are responsible for the interactions of different effectors. These findings shed light on the molecular basis for the interactions of Gbetagamma with Ca2+-CaM and point to the potential physiological significance of these interactions in cellular functions.

Adenosine Diphosphate Ribose↗
PubMed1997

New families with von Willebrand disease type 2M (Vicenza).

The variant von Willebrand disease (vWd) variant type 2M (Vicenza) was identified in 13 patients of 7 unrelated families. 11 patients were from different parts of germany and 2 patients from Turkey. Hitherto this variant of vWd has been described only in two families originating from the province of Vicenza in Northern Italy. Characteristically this type of vWd shows the supranormal multimers of von Willebrand factor (vWf) in plasma similar to those seen in normal plasma after desmopressin infusion. Clinically, the patients present with bleeding symptoms. Other laboratory abnormalities include reduced values for vWf antigen (vWf: Ag), factor VIII coagulant activity (VII:C), ristocetin cofactor activity (RiCof) and collagen binding activity (vWf: CBA). The hereditary transmission of this variant is consistent with an autosomal dominant mode of inheritance. The patients with vWd type 2M (Vicenza) could be allocated into two subgroups: type "platelet normal" with normal vWf properties in platelets and type "platelet low" with reduced vWf: Ag levels in platelets.

Adult↗