Biomedical subjects

D Vogt

Publications and source records attributed to D Vogt.

At least 19 recordsLinked to original sources

PubMed2001

Asymmetric nickel-catalyzed hydrocyanation of vinylarenes by applying homochiral xantphos ligands.

New homochiral xantphos-type diphosphonite ligands with binaphthoxy substituents have been prepared and characterized by NMR spectroscopy. These ligands have been applied in the nickel-catalyzed hydrocyanation of styrene and other vinylarenes. Enantioselectivities up to 63% ee have been obtained by using 4-isobutylstyrene as a substrate. Addition of an excess of ligand strongly inhibits the hydrocyanation reaction since the bis-chelate nickel complexes formed are highly stable and catalytically inactive.

Journal Article↗

PubMed2000

Phosphino carboxylic acid ester functionalized carbosilane dendrimers: nanoscale ligands for the Pd-catalyzed hydrovinylation reaction in a membrane reactor

Phosphino carboxylic acid ester terminated G(0) compounds Si(CH(2))(3)SiMe(2)(C(6)H(4)CH(2)OC(O)(CH(2))(n)()CH(2)PPh(2)(4) (9a and 9b; n = 1, 2) and the carbosilane dendrimers Si(CH(2))(3)Si((CH(2))(3)SiMe(2)(C(6)H(4)CH(2)OC(O)(CH(2))(n)()CH(2) PPh(2))(3)(4) (10a and 10b; n = 1, 2) have been prepared as hemilabile nanoscale ligands for the palladium-catalyzed codimerization of olefins. The hydrovinylation of styrene was carried out in a continuously operated nanofiltration membrane reactor. Under continuous conditions, the selectivity of the reaction is increased considerably. Monomeric model complexes and the dendritic catalysts were compared for their activity and selectivity in batch reactions. The Pd catalyst complexes were prepared in situ from the dendritic ligands and an (allyl)palladium(II) precursor.

Journal Article↗

PubMed2000

Application of P-stereogenic aminophosphine phosphinite ligands in asymmetric hydroformylation

New chiral aminophosphine phosphinite ligands with a stereogenic center at the aminophosphine phosphorus atom were prepared based on (R,S)-ephedrine as the chiral auxiliary and backbone. Substituents at the chiral aminophosphine as well as at the phosphinite phosphorus atom were varied. These new ligands were applied to the rhodium-catalyzed asymmetric hydroformylation of vinyl arenes. The enantiomeric excess reached up to 77%. 1H and 31P NMR studies of the Rh complexes under syngas pressure reveal that [HRh(CO)2(PP)] complexes with the NP* moiety in an axial position are responsible for enantioselectivity.

Journal Article↗

PubMed2000

Giant cell angiofibroma of the inguinal region.

Giant cell angiofibroma is a rare mesenchymal neoplasm most commonly arising in the soft tissues near the orbit. Recently, several cases of extraorbital giant cell angiofibroma have been reported. We report the light microscopic and immunohistochemical features of an additional case of extraorbital giant cell angiofibroma arising in the inguinal region that was clinically mistaken for an inguinal hernia. The patient was a 50-year-old woman who presented with a mobile, nonreducible, left inguinal mass. The tumor was 10.8 cm in greatest diameter, was well circumscribed, and appeared to be encapsulated. Histologically, the tumor was composed of a mixture of cytologically bland spindle-shaped cells and ovoid cells of varying cellularity with deposition in a variably collagenous and myxoid stroma. The tumor had prominent, various-sized blood vessels, often with perivascular hyalinization. In addition, scattered pseudovascular spaces filled with an amorphous eosinophilic material were present and lined by spindle-shaped and ovoid cells similar to those found throughout the neoplasm. Rare multinucleated floret-like giant cells were seen. Immunohistochemically, the tumor cells stained strongly and diffusely for both CD34 and bcl-2 while immunostains for S-100 protein, desmin, smooth muscle actin, and muscle-specific actin were negative. There is no evidence of local recurrence or metastasis 3 months following excision of the mass. This report emphasizes the recognition of this unusual tumor in extraorbital sites. We discuss the overlapping histologic and immunophenotypic features with giant cell fibroblastoma and solitary fibrous tumor and raise the possibility that these tumors could represent a histologic spectrum of CD34-positive dendritic interstitial cell neoplasms.

Abdominal Neoplasms↗

PubMed2000

Molecular cloning of Xp11 breakpoints in two unrelated mentally retarded females with X;autosome translocations.

Mental retardation is a very common and extremely heterogeneous disorder that affects about 3% of the human population. Its molecular basis is largely unknown, but many loci have been mapped to the X chromosome. We report on two mentally retarded females with X;autosome translocations and breakpoints in Xp11, viz., t(X;17)(p11;p13) and t(X;20)(p11;q13). (Fiber-) FISH analysis assigned the breakpoints to different subbands, Xp11.4 and Xp11.23, separated by approximately 8 Mb. High-resolution mapping of the X- chromosome breakpoints using Southern blot hybridization resulted in the isolation of breakpoint-spanning genomic subclones of 3 kb and 0. 5 kb. The Xp11.4 breakpoint is contained within a single copy sequence, whereas the Xp11.23 breakpoint sequence resembles an L1 repetitive element. Several expressed sequences map close to the breakpoints, but none was found to be inactivated. Therefore, mechanisms other than disruption of X-chromosome genes likely cause the phenotypes.

Adolescent↗

PubMed1999

Guanosine triphosphatase stimulation of oncogenic Ras mutants.

Interest in the guanosine triphosphatase (GTPase) reaction of Ras as a molecular drug target stems from the observation that, in a large number of human tumors, Ras is characteristically mutated at codons 12 or 61, more rarely 13. Impaired GTPase activity, even in the presence of GTPase activating proteins, has been found to be the biochemical reason behind the oncogenicity of most Gly12/Gln61 mutations, thus preventing Ras from being switched off. Therefore, these oncogenic Ras mutants remain constitutively activated and contribute to the neoplastic phenotype of tumor cells. Here, we show that the guanosine 5'-triphosphate (GTP) analogue diaminobenzophenone-phosphoroamidate-GTP (DABP-GTP) is hydrolyzed by wild-type Ras but more efficiently by frequently occurring oncogenic Ras mutants, to yield guanosine 5'-diphosphate-bound inactive Ras and DABP-Pi. The reaction is independent of the presence of Gln61 and is most dramatically enhanced with Gly12 mutants. Thus, the defective GTPase reaction of the oncogenic Ras mutants can be rescued by using DABP-GTP instead of GTP, arguing that the GTPase switch of Ras is not irreversibly damaged. An exocyclic aromatic amino group of DABP-GTP is critical for the reaction and bypasses the putative rate-limiting step of the intrinsic Ras GTPase reaction. The crystal structures of Ras-bound DABP-beta,gamma-imido-GTP show a disordered switch I and identify the Gly12/Gly13 region as the hydrophobic patch to accommodate the DABP-moiety. The biochemical and structural studies help to define the requirements for the design of anti-Ras drugs aimed at the blocked GTPase reaction.

Benzophenones↗

PubMed1999

An evaluation of two methods for chronic central venous access device placement.

BACKGROUND: Chronic venous access devices (CVADs), placed for phlebotomy and the administration of medications and nutrition, require fluoroscopy to confirm correct catheter position. Long-term central venous catheters placed using an electromagnetic catheter locating system (EMCLS) could result in decreased radiation exposure and decreased cost without compromising accuracy of position. METHODS: Charts of patients who underwent placement of CVADs at University of New Mexico (UNM) Hospital or UNM Cancer Center were reviewed. Inclusion criteria included age >20 years and placement of a central CVAD utilizing fluoroscopy (group 1) or the EMCLS (group 2). Radiation exposure, complications, cost, and accuracy of placement were determined for each technique. RESULTS: Between June 1996 and June 1998, 196 patients underwent placement of CVADs. Complete data sets were available for 46 patients in each group. There were no statistically significant differences in age, gender, complications, or operating room times (P = 0.26). Fluoroscopy and EMCLS were equally accurate for the correct placement of the tip of the line (P = 0.12). Mean patient radiation exposure was EMCLS, 30 mRem, and fluoroscopy, 771 mRem. EMCLS significantly decreased cost (P = 0.025) when compared with fluoroscopic assisted catheter placement. CONCLUSIONS: The use of EMCLS for CVAD placement reduces radiation exposure and cost without compromising the accuracy of placement when compared with standard fluoroscopic-assisted placement.

Catheterization, Central Venous↗

PubMed1999

The Ras mutant D119N is both dominant negative and activated.

The introduction of mutation D119N (or its homolog) in the NKxD nucleotide binding motif of various Ras-like proteins produces constitutively activated or dominant-negative effects, depending on the system and assay. Here we show that Ras(D119N) has an inhibitory effect at a cell-specific concentration in PC12 and NIH 3T3 cells. Biochemical data strongly suggest that the predominant effect of mutation D119N in Ras-a strong decrease in nucleotide affinity-enables this mutant (i) to sequester its guanine nucleotide exchange factor, as well as (ii) to rapidly bind GTP, independent of the regulatory action of the exchange factor. Since mutation D119N does not affect the interaction between Ras and effector molecules, the latter effect causes Ras(D119N) to act as an activated Ras protein at concentrations higher than that of the exchange factor. In comparison, Ras(S17N), which also shows a strongly decreased nucleotide affinity, does not bind to effector molecules. These results point to two important prerequisites of dominant-negative Ras mutants: an increased relative affinity of the mutated Ras for the exchange factor over that for the nucleotide and an inability to interact with the effector or effectors. Remarkably, the introduction of a second, partial-loss-of-function, mutation turns Ras(D119N) into a strong dominant-negative mutant even at high concentrations, as demonstrated by the inhibitory effects of Ras(E37G/D119N) on nerve growth factor-mediated neurite outgrowth in PC12 cells and Ras(T35S/D119N) on fetal calf serum-mediated DNA synthesis in NIH 3T3 cells. Interpretations of these results are discussed.

3T3 Cells↗

PubMed1997

A randomized clinical trial of ursodeoxycholic acid as adjuvant treatment to prevent liver transplant rejection.

Acute rejection following orthotopic liver transplantation is a common problem despite current immunosuppressive regimens. Ursodeoxycholic acid (UDCA) has been shown in small, open-labeled studies to prevent rejection episodes, although its effects on complications such as infections, length of hospital stay, and survival have not been evaluated. We conducted a randomized, placebo-controlled, double-blind trial to determine if UDCA (10-15 mg/kg/d) added to a cyclosporine-based immunosuppressive regimen was associated with a decrease in the incidence of at least one episode of acute cellular rejection. Secondary end-points included determining differences in the total number of rejection episodes, the use of muromonab-CD3, the incidence of infections, length of hospital stay, and survival at 90 days and 1 year. Fifty-two patients were randomized, 28 to the treatment group and 24 to the placebo group. During the 3 months of the trial, there was no difference between the placebo and UDCA groups in the number of patients who were rejection-free; however, there were significantly fewer patients in the treatment group who had multiple episodes of acute rejection (0 vs. 6; P = .007). Patients in the treatment group experienced a significantly lower incidence of bacterial infections (4% vs. 29%; P = .02), shorter hospital stay (25 days vs. 34 days; P = .03), and better 90-day survival (100% vs. 83%; P = .04) and 1-year survival (93% vs. 79%). The addition of UDCA to a cyclosporine-based immunosuppressive regimen results in significantly fewer patients experiencing multiple episodes of rejection and improved survival at 90 days and at 1 year. The use of UDCA as adjuvant therapy for patients undergoing liver transplantation who are treated with a cyclosporine-based immunosuppressive regimen should be considered.

Adult↗

PubMed1997

Successful treatment of esophageal achalasia with laparoscopic Heller myotomy and Toupet fundoplication.

BACKGROUND: Recently, investigators have reported the use of endoscopic myotomy in the treatment of esophageal achalasia. As with the open operation, considerable disagreement exists regarding the appropriate length of the myotomy and the need for a concomitant antireflux procedure. METHODS: Patients presenting with symptomatic achalasia between 1993 and 1997 were included in this prospective study. Preoperative studies included barium upper gastrointestinal study, endoscopy, and esophageal manometry. Laparoscopic myotomy was completed in all 20 patients; 18 had concomitant Toupet fundoplication. RESULTS: Operative times ranged from 95 to 345 minutes (mean 216). Blood loss ranged from 50 to 300 cc (mean 100 cc). There were 7 minor complications (5 mucosal injuries repaired laparoscopically, 1 bile leak and 1 splenic capsular tear). Nine patients began a liquid diet on the first day postoperatively; 19 were tolerating liquids by postoperative day 3. Hospital stay ranged from 2 to 20 days (mean 5). Eighteen patients had complete relief of dysphagia, with less than one reflux episode per month. One individual continues to have mild persistent solid food dysphagia. Another patient initially did well but subsequently developed mild recurrent dysphagia and reflux. One patient required laparoscopic take-down of the wrap because of recurrent dysphagia and now has no problems swallowing, but does complain of mild reflux. Two other patients also have mild reflux, 1 of whom did not undergo fundoplication. CONCLUSIONS: Laparoscopic Heller myotomy can be performed safely with excellent results in patients with achalasia. Adding a partial fundoplication appears to help control postoperative symptoms of reflux. This procedure should be considered the procedure of choice in patients with symptomatic esophageal achalasia.

Adolescent↗

PubMed1997

Isolated splenic metastases from colon cancer.

Metastatic tumors of the spleen are rare and usually occur in the presence of disseminated visceral metastases. The liver is the most common site of metastatic spread from colon cancer. We report a case of isolated intrasplenic metastasis from sigmoid colon cancer and review the possible reasons for the rarity of splenic metastasis. This represents the fifth reported case of isolated splenic metastasis from colon cancer. Splenectomy may be justified in presence of isolated metastatic disease, since it is an operation with a low complication rate and may provide potential long-term survival in colon cancer.

Adenocarcinoma↗

PubMed1995

Prevalence and reversibility of the hepatopulmonary syndrome after liver transplantation. The Cleveland Clinic experience.

To ascertain the prevalence and reversibility of the hepatopulmonary syndrome, we reviewed the cases of 98 patients undergoing liver transplantation at the Cleveland (Ohio) Clinic Foundation from June 1988 through July 1992 and identified 4 patients with clinically recognized hepatopulmonary syndrome (prevalence 4%). All 4 patients ultimately had complete reversal of their disorder. As reviewed herein, the prevalence of the hepatopulmonary syndrome in the current series is lower than in previous reports, possibly reflecting a dependence on its clinical recognition in this series rather than the use of routine screening tests. This report confirms previous experience that the hepatopulmonary syndrome may be reversible after transplantation.

Adult↗

PubMed1994

Pharmacokinetics and haemodynamic effects of ISDN following different dosage forms and routes of administration.

The pharmacokinetics and haemodynamic effects of isosorbide dinitrate (ISDN) have been investigated following administration of single doses as a sublingual (SL) spray (2.5 mg), sublingual tablet (5 mg) and peroral tablet (10 mg) in a randomised, placebo-controlled double-blind cross-over trial in 16 healthy volunteers. After the sublingual spray Cmax was higher (39.0 ng.ml-1) and tmax was shorter (3.9 min) than after the sublingual (22.8 ng.ml-1 and 13.8 min) and peroral (16.9 ng.ml-1 and 25.6 min) tablets. The AUC of ISDN did not differ following any of the three formulations (1031; 879; 997 ng.ml-1.min, for the spray, SL tablet and PO-tablet, respectively). Mononitrate metabolites of ISDN (IS-2-MN and IS-5-MN) and total nitrates in plasma increased in proportion to the administered dose. This indicates that the fraction of the dose absorbed was the same for all the formulations but that the extent of first-pass metabolism increased in the order sublingual spray < sublingual tablet < peroral tablet. Thus, compared to the spray, the relative bioavailability of ISDN was 48% and 28% from the sublingual and peroral tablets, respectively. The haemodynamic effects were quantified using the a/b ratio of the finger pulse wave and the systolic blood pressure and heart rate under orthostatic conditions.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗

PubMed1994

Successful management of severe gastroesophageal reflux disease with laparoscopic Nissen fundoplication.

BACKGROUND: Nissen fundoplication has been shown to be superior to medical treatment in the management of severe or complicated gastroesophageal reflux disease (GERD). Rapid advances in minimally invasive surgical technique and recognition of the advantages of reduced incision-related morbidity have fostered application of laparoscopic techniques to antireflux surgery. A prospective evaluation of 70 patients undergoing laparoscopic Nissen fundoplication for severe GERD was undertaken. PATIENTS AND METHODS: Rigid selection criteria for laparoscopic Nissen fundoplication included severe or refractory disease with documentation of abnormal esophageal acid exposure by 24-hour pH probe monitoring, documentation of a mechanically defective lower esophageal sphincter by esophageal manometry, and absence of severe esophageal and/or gastric motility disorders. RESULTS: Sixty-eight of 70 patients were completed laparoscopically with an intraoperative morbidity rate of 9%. Major postoperative complications occurred in 3 patients (4%) and included deep venous thrombosis (n = 1), delayed gastric leak (n = 1), and trocar site hernia (n = 1). The average hospital stay was 3.0 days, and the average time to return to normal activity was 7.0 days. All patients experienced relief of symptoms of reflux with mean follow-up of 7.7 months. Transient, mild dysphagia was experienced by 37% of patients, and persistent, severe dysphagia by 7%. The mean increase in lower esophageal sphincter pressure was 16.2 mm Hg. The total and intra-abdominal sphincter lengths increased an average of 1.5 and 1.4 cm, respectively. CONCLUSIONS: These preliminary data suggest that laparoscopic Nissen fundoplication can be performed by experienced laparoscopic surgeons with excellent symptomatic and physiologic results and a morbidity rate comparable to conventional open antireflux procedures. Rigid patient selection criteria will help identify the patients most likely to benefit from reconstruction of a mechanically defective lower esophageal sphincter. Adherence to established operative principles for Nissen fundoplication will reduce the incidence of significant postfundoplication symptoms.

Adult↗

PubMed1993

The small GTP-binding protein, Rab6p, is associated with both Golgi and post-Golgi synaptophysin-containing membranes during synaptogenesis of hypothalamic neurons in culture.

We have recently localized a small GTP-binding protein (Rab6p) thought to be involved in vesicular membrane transport, to the medial and trans-cisternae of the Golgi apparatus in NRK (normal rat kidney) cells. Here, we have localized and quantified Rab6p during the development in culture of embryonic neurons, up to synapse formation, and compared its subcellular distribution and level of expression to that of synaptophysin, a major integral membrane protein of small synaptic vesicles. Using immunocytochemistry (laser scanning confocal microscopy, immunoelectron microscopy), fractionation and immunoisolation methods, we show that during the early phase of synaptogenesis, Rab6p is associated with synaptophysin-containing membranes of a trans-Golgi subcompartment, post-Golgi vesicles and small synaptic vesicles or their precursors. Concomitantly, Rab6p undergoes translocation from cytosol to membranes and its level of expression increases. However, at late stages, the association of Rab6p to small synaptic vesicles sharply decreases and its level of expression plateaus. These findings suggest a role for Rab6p in the post-Golgi transport of synaptophysin, at an early step of the biogenesis of small synaptic vesicles.

Animals↗

PubMed1992

An amphicrine pancreatic cell line: AR42J cells combine exocrine and neuroendocrine properties.

The permanent cell culture line AR42J, derived from a rat pancreatic acinar carcinoma, is widely used for functional studies of exocrine pancreatic acinar cells. We now present evidence that these cells are amphicrine in that they contain zymogen granules as well as small (40-80 nm) neuroendocrine (NE) vesicles and typical neurotransmitters. Using the small NE vesicle-specific markers synaptophysin and "protein S.V.2", including synaptophysin cDNA probes, we have found that AR42J cells synthesize these proteins and contain vesicles harboring these proteins with biophysical properties similar to those of small NE vesicles. NE properties of these cells are further indicated by the presence of considerable amounts of stored amino acids (gamma-aminobutyric acid (GABA), glycine, glutamate) and by the presence of the GABA-synthesizing enzyme, glutamic acid decarboxylase. Finally, intermediate filament (IF) protein typing showed only cytokeratins 8 and 18, indicating that AR42J cells possess an IF protein complement indistinguishable from that of acinar and islet cells. Our results document the unusual case of a permanent cell line with combined exocrine and neuroendocrine properties that may be indicative of a derivation from a cell with multipotential character.

Animals↗

PubMed1992

Familial nonmultiple endocrine neoplasia medullary thyroid carcinoma: an evolving clinical entity.

BACKGROUND: A rare kindred of familial nonmultiple endocrine neoplasia medullary thyroid carcinoma arising from a 73-year-old proband case is reported to further define this distinct entity. METHODS: Twenty-four family members across four generations, four with medullary thyroid carcinoma (MTC) and two with C-cell hyperplasia (CCH), were studied. RESULTS: Basal calcitonin levels were elevated in three patients with MTC and were normal in one patient with microscopic MTC and two patients with CCH who had persistent subtle elevation in calcium and/or pentagastrin-stimulated calcitonin levels. One patient had unilateral MTC without CCH. Associated abnormalities included papillary carcinoma (2), thyroiditis (4), adenoma (2), and colloid nodule (1). Minimum treatment was total thyroidectomy. Two patients with MTC and marked hypercalcitonemia have recurrent disease at 2.5-year and 11-year follow-up. Two patients with MTC and normal or minor elevations in basal calcitonin and two with CCH had normal provocative calcitonin testing at 6 to 18 months follow-up. CONCLUSIONS: Unilateral MTC without CCH and MTC in the elderly do not preclude a familial cause. Microscopic MTC or CCH may be seen with subtle elevations in stimulated calcitonin levels, and recognition allows for curative thyroidectomy. Other apparent dominant thyroid pathologic conditions may occur concomitantly with familial medullary thyroid carcinoma and thus routine calcitonin, and immunohistochemical testing should be performed in patients with an appropriate family history.

Adult↗

PubMed1990

Reduction of intrapulmonary shunt and resolution of digital clubbing associated with primary biliary cirrhosis after liver transplantation.

This report describes a patient with marked hypoxemia caused by intrapulmonary shunt associated with primary biliary cirrhosis. Liver transplantation resulted in resolution of digital clubbing and reduction of intrapulmonary shunt as demonstrated by normalization of room air arterial blood gases, reduction in shunt fraction and normalization of the indocyanine-enhanced echocardiogram and perfusion lung scan. This patient's course challenges the conventional notion that intrapulmonary shunting associated with chronic liver disease does not reverse after liver transplantation.

Adult↗