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J Wolf

Publications and source records attributed to J Wolf.

At least 73 records · Page 4Linked to original sources

The identification and development of specific monoclonal antibodies to squamous cell carcinoma.

We have developed specific monoclonal antibodies to immunogenic glycoproteins expressed selectively on the cell membrane of squamous cell malignancies. These proteins serve to act as tumor markers that characterize this malignancy; there has be no evidence of cross reactivity to normal epithelial cells. Analysis of patterns of expression reveals that those membrane proteins identified by monoclonals AD7 and 5C6 appear early in cellular transformation to malignancy. At such a time, immunohistochemical recognition is seen in the presence of genotypic alterations, yet phenotypic changes may not be apparent. Of additional interest is that these monoclonal antibodies exhibit strong ADCC allowing the tumor proteins to not only serve as a marker of malignancy but as a target for therapeutic destruction.

Animals↗

Carbenerhodium complexes of the half-sandwich-type: synthesis, substitution, and addition reactions.

A series of carbenerhodium(I) complexes of the general composition [(eta5-C5H5)Rh(=CRR')(L)] (2a-2i) with R = R'= aryl and L = SbiPr3 or PR3 has been prepared from the square-planar precursors trans-[RhCl(=CRR')(L)2] and NaC5H5 in excellent yields. Reaction of the triisopropylsibane derivative 2a. which contains a rather labile Rh-Sb bond, with CO, PMe3, and CNR (R = Me, CH2Ph, tBu) leads to the displacement of the SbiPr3 ligand and affords the substitution products [(eta5-C5H5)Rh(=CPh2)(L)] (3-7). In contrast, treatment of the triisopropylphosphane compound 2c with CO and CNtBu leads to the cleavage of the Rh=CPh2 bond and gives besides [(eta5-C5H5)Rh(PiPr3)(L)] (10, 12) by metal-assisted C-C coupling diphenylketene Ph2C=C=O (11) or the corresponding imine Ph2C=C=NtBu (13). While the reaction of 2a, c with C2H4 yields [(eta5-C5H5)Rh(C2H4)(L)] (14, 15) and the trisubstituted olefin Ph2C=CHCH3 (16), treatment of 2a, c with RN3 leads to the cleavage of both the Rh-EiPr3 and Rh=CPh2 bonds and gives the chelate complexes [(eta5-C5H5)Rh(kappa2-RNNNNR)] (19, 20). The substitution products 3 (L=CO) and 4 (L= PMe3) react with an equimolar amount of sulfur or selenium by addition of the chalcogen to the Rh=CPh2 bond to generate the complexes [(eta5-C5H5)Rh(kappa2-ECPh2)(L)] (21-24) with thio- or selenobenzophenone as ligand. Similarly, treatment of 3 with CuCl affords the unusual 1:2 adduct [(eta5-C5H5)(CO)Rh(mu-CPh2)(CuCl)2] (25), which reacts with NaC5H5 to form [(eta5-C5H5)(CO)Rh(muCPh2)Cu(eta5-C5H5)] (26). The molecular structures of 3 and 22 have been determined by X-ray crystallography.

Journal Article↗

The bridging function of an apparently nonbridging ligand: dinuclear rhodium complexes with Rh(mu-SbR3)Rh as a molecular unit.

Novel dinuclear rhodium complexes of the general composition [Rh2Cl2(mu-CRR')2(mu-SbiPr3)] (4-6) were prepared by thermolysis of the mononuclear precursors trans-[RhCl(=CRR')(SbiPr3)2] in excellent yield. The X-ray crystal structure analysis of 4 (R = R' = Ph) confirms the symmetrical bridging position of the stibane ligand. Related compounds [Rh2Cl2(mu-CPh2)(mu-CRR')(mu-SbiPr3)] (7, 8) with two different carbene units were obtained either from trans-[RhCl(=CPh2)(SbiPr3)2] (1) and RR'CN2 or by a conproportionation of 4 and 5 (R = R' = p-Tol) or 4 and 6 (R= Ph, R' = p-Tol), respectively. While CO reacts with 4 to give the polymeric product [[RhCl(CPh2)(CO)]n] (9), tert-butyl isocyanide replaces the bridging stibane and yields [Rh2Cl2(mu-CPh2)2(mu-CNtBu)] (10). The reaction of 4 with tertiary phosphanes PR3 leads to complete bridge cleavage and affords the mononuclear compounds trans-[RhCl(=CPh2)(PR3)2] (11-15). In contrast, treatment of 4 with SbMe3 and SbEt3 yields the related triply bridged complexes [Rh2Cl2(mu-CPh2)2(mu-SbR3)] (16, 17) by substitution of SbiPr3 for the smaller stibanes. The displacement of the chloro ligands in 4-6 and 10 by n5-cyclopentadienyl gives the dinuclear complexes [(n5-C5H5)2Rh2(mu-CRR')2] (18-20) and [(n5-C5H5)2Rh2(mu-CPh2)2(mu-CNtBu)] (21), of which 18 (R = R' = Ph) was characterized crystallographically.

Journal Article↗

Somatic mutations of the CD95 gene in Hodgkin and Reed-Sternberg cells.

Hodgkin and Reed-Sternberg (H/RS) cells in classical Hodgkin's disease (cHD) are thought to be derived from preapoptotic germinal center B cells. However, little is known about the transforming events rescuing the precursor of the H/RS cells from apoptosis. Given the importance of CD95 (Apo-1/Fas)-mediated apoptosis for negative selection within the germinal center, single micromanipulated H/RS cells from 10 cases of cHD were analyzed for somatic mutations within the CD95 gene. Three clonal mutations within the 5' regions were amplified from single H/RS cells in one case. From H/RS cells of another case, two mutations within the last exon coding for the death domain were detected. About half of these H/RS cells carried a monoallelic stop-codon; the remaining tumor cells harbored a monoallelic replacement mutation. Both mutations likely impair CD95 function. Because all these H/RS cells also bear clonal mutations inactivating the IkappaB alpha gene, the IkappaB alpha mutations occurred earlier than those of the CD95 gene in the sequence of transforming events leading to cHD. In conclusion, somatic mutations of the CD95 gene occur in a fraction of cHD cases and may favor the escape of the precursor of the H/RS clone from apoptosis.

Adult↗

Cationic and neutral diphenyldiazomethanerhodium(I) complexes as catalytically active species in the C-C coupling reaction of olefins and diphenyldiazomethane

Cationic rhodium(I) complexes cis-[Rh(acetone)2(L)(L')]+ (2: L = L'=C8H14; 3: L=C8H14; L'=PiPr3; 4: L=L'=PiPr3), prepared from [RhCl(C8H14)2]2] and isolated as PF6 salts, catalyze the C-C coupling reaction of diphenyldiazomethane with ethene, propene, and styrene. In most cases, a mixture of isomeric olefins and cyclopropanes were obtained which are formally built up by one equivalent of RCH=CH2 (R = H, Me, Ph) and one equivalent of CPh2. The efficiency and selectivity of the catalyst depends significantly on the coordination sphere around the rhodium(I) center. Treatment of 4 with Ph2CN2 in the molar ratio of 1:1 and 1:2 gave the complexes trans-[Rh(PiPr3)2(acetone)(eta1-N2CPh2)]PF6 (8) and trans-[Rh(PiPr3)2(eta1-N2CPh2)2]PF6 (9), of which 8 was characterized by X-ray crystallography. Since 8 and 9 not only react with ethene but also catalyze the reaction of C2H4 and free Ph2CN2, they can be regarded as intermediates (possibly resting states) in the C-C coupling process. The lability of 8 and 9 is illustrated by the reactions with pyridine and NaX (X=Cl, Br, I, N3) which afford the mono(diphenyldiazomethane)rhodium(I) compounds trans-[Rh(PiPr3)2(py)(eta1-N2CPh2)]PF6 (10) and trans-[RhX(eta1-N2CPh2)(PiPr3)2] (11-14), respectively. The catalytic activity of the neutral complexes 11 - 14 is somewhat less than that of the cationic species 8, 9 and decreases in the order Cl > Br> I > N3.

Journal Article↗

Suppression of the tumorigenic growth of Burkitt's lymphoma cells in immunodeficient mice by cytokine gene transfer using EBV-derived episomal expression vectors.

Epstein-Barr virus (EBV)-based expression vectors were tested for cytokine gene transfer-mediated induction of an immune response against human lymphoma cells. These vectors express the EBV latent gene EBNA 1 and carry the EBV latent origin of replication (ori P) for episomal replication in transfected cells. In addition, 3 human immunoglobulin light chain enhancer elements augment expression in B-cells. The suitability of these vectors for expression of cytokine genes in human lymphoma cells in vitro has been demonstrated. In order to extend these experiments in vivo, highly tumorigenic Burkitt's lymphoma (BL) cells were transfected with different cytokine genes of human and murine origin cloned into the EBNA 1/ori P vectors. Tumorigenicity of the transfectants was measured after inoculation into nude mice. No effect on tumorigenicity was observed after hIL 6 transfection and an inconsistent effect after hTNFalpha transfection. In contrast, complete suppression of tumor outgrowth occurred in hIL 10 transfectants. This tumor suppressive effect, however, was restricted to the IL 10 transfectants themselves and not directed against non-transfected cells. By comparison, mIL 4 transfected BL cells also were non-tumorigenic. However, co-inoculation of mIL 4 transfected and non transfected cells resulted in suppression of the tumorigenicity of the non-transfected cells. Thus, highly tumorigenic BL cells in nude mice are sensitive to immune effector mechanisms triggered by cytokine expression. In this experimental model, EBNA 1/ori P expression vectors are a suitable tool for cytokine gene transfer mediated induction of an anti-lymphoma immune response of the host.

Animals↗

Search for neutrino oscillations at the palo verde nuclear reactors

We report on the initial results from a measurement of the antineutrino flux and spectrum at a distance of about 800 m from the three reactors of the Palo Verde Nuclear Generating Station using a segmented gadolinium-loaded scintillation detector. We find that the antineutrino flux agrees with that predicted in the absence of oscillations excluding at 90% C.L. nu;(e)-nu;(x) oscillations with Deltam(2)>1.12x10(-3) eV(2) for maximal mixing and sin (2)2straight theta>0.21 for large Deltam(2). Our results support the conclusion that the atmospheric neutrino oscillations observed by Super-Kamiokande do not involve nu(e).

Journal Article↗

Clonal deleterious mutations in the IkappaBalpha gene in the malignant cells in Hodgkin's lymphoma.

Members of the nuclear factor (NF)-kappaB family of transcription factors play a crucial role in cellular activation, immune responses, and oncogenesis. In most cells, they are kept inactive in the cytosol by complex formation with members of the inhibitor of NF-kappaB (IkappaB) family, whose degradation activates NF-kappaB in response to diverse stimuli. In Hodgkin's lymphoma (HL), high constitutive nuclear activity of NF-kappaB is characteristic of the malignant Hodgkin and Reed-Sternberg (H/RS) cells, which occur at low number in a background of nonneoplastic inflammatory cells. In single H/RS cells micromanipulated from histological sections of HL, we detect clonal deleterious somatic mutations in the IkappaBalpha gene in two of three Epstein-Barr virus (EBV)-negative cases but not in two EBV-positive cases (in which a viral oncogene may account for NF-kappaB activation). There was no evidence for IkappaBalpha mutations in two non-HL entities or in normal germinal center B cells. This study establishes deleterious IkappaBalpha mutations as the first recurrent genetic defect found in H/RS cells, indicating a role of IkappaBalpha defects in the pathogenesis of HL and implying that IkappaBalpha is a tumor suppressor gene.

Adult↗

Effect of cellular interaction on glycolytic oscillations in yeast: a theoretical investigation.

On the basis of a detailed model of yeast glycolysis, the effect of intercellular dynamics is analysed theoretically. The model includes the main steps of anaerobic glycolysis, and the production of ethanol and glycerol. Transmembrane diffusion of acetaldehyde is included, since it has been hypothesized that this substance mediates the interaction. Depending on the kinetic parameter, the single-cell model shows both stationary and oscillatory behaviour. This agrees with experimental data with respect to metabolite concentrations and phase shifts. The inclusion of intercellular coupling leads to a variety of dynamical modes, such as synchronous oscillations, and different kinds of asynchronous behavior. These oscillations can co-exist, leading to bi- and tri-rhythmicity. The corresponding parameter regions have been identified by a bifurcation analysis. The oscillatory dynamics of synchronized cell populations are investigated by calculating the phase responses to acetaldehyde pulses. Simulations are performed with respect to the synchronization of two subpopulations that are oscillating out of phase before mixing. The effect of the various process on synchronization is characterized quantitatively. While continuous exchange of acetaldehyde might synchronize the oscillations for appropriate sets of parameter values, the calculated synchronization time is longer than that observed experimentally. It is concluded either that addition to the transmembrane exchange of acetaldehyde, other processes may contribute to intercellular coupling, or that intracellular regulator feedback plays a role in the acceleration of the synchronization. for appropriate sets of parameter values, the calculated synchronization time is longer than that observed experimentally. It is concluded either that addition to the transmembrane exchange of acetaldehyde, other processes may contribute to intercellular coupling, or that intracellular regulator feedback plays a role in the acceleration of the synchronization.

Acetaldehyde↗

Detection of Epstein-Barr virus in Hodgkin-Reed-Sternberg cells : no evidence for the persistence of integrated viral fragments inLatent membrane protein-1 (LMP-1)-negative classical Hodgkin's disease.

Classical Hodgkin's disease (HD) is associated with Epstein-Barr virus (EBV) infection. Although in developing countries EBV can be demonstrated in Hodgkin-Reed-Sternberg (H-RS) cells in up to 95% of HD cases, in industrialized countries only about 50% of HD cases are associated with EBV. An open question remains whether EBV in the EBV-negative cases has escaped detection by standard screening procedures due to deletions in the viral genome associated with integration of viral fragments into the host cell genome. We, among others, recently described this phenomenon in Burkitt's lymphoma cells. To investigate whether H-RS cells in latent membrane protein-1 (LMP-1)-negative HD cases harbor fragments of the EBV genome, we combined fluorescence in situ hybridization (FISH) using a set of six overlapping DNA probes spanning the whole EBV genome with immunophenotyping of fresh frozen lymphoma sections. Results in the eight cases analyzed were as follows: in three LMP-1-positive cases, FISH analysis yielded specific signals for each EBV DNA probe in H-RS cells, which had been identified by morphology and CD30 staining. In contrast, none of the EBV DNA probes hybridized to the H-RS cells in the five LMP-1-negative cases. Thus, there is no evidence for the presence of fragments of the viral genome integrated into the host cell genome in the LMP-1-negative cases. Furthermore, in the LMP-1-positive cases analyzed, no large deletions in the viral genome were detected. These results show that, in classical HD, LMP-1-negative cases do not harbor EBV DNA within the H-RS cells. Whether, in these cases, a still unknown virus contributes to the transformation and maintenance of the malignant phenotype remains to be established.

Adolescent↗

Transduction of intracellular and intercellular dynamics in yeast glycolytic oscillations.

Under certain well-defined conditions, a population of yeast cells exhibits glycolytic oscillations that synchronize through intercellular acetaldehyde. This implies that the dynamic phenomenon of the oscillation propagates within and between cells. We here develop a method to establish by which route dynamics propagate through a biological reaction network. Application of the method to yeast demonstrates how the oscillations and the synchronization signal can be transduced. That transduction is not so much through the backbone of glycolysis, as via the Gibbs energy and redox coenzyme couples (ATP/ADP, and NADH/NAD), and via both intra- and intercellular acetaldehyde.

Acetaldehyde↗

Quality evaluation of young adults' radiographs in Finnish public oral health service.

OBJECTIVE: To evaluate the quality of young adults' radiographs exposed and processed under everyday clinical conditions. SETTING: One administrative unit of the Finnish public oral health service. DESIGN: Two reviewers independently evaluated the radiographs by the same written criteria that were designed as a checklist for on-site evaluations, without any further calibration. SAMPLE: In total, 312 radiographs (178 bitewing, 88 periapical and 46 panoramic) from 1990 to 1996, collected from patient documents of a randomly selected sample of young adults born in 1966-1971. OUTCOME MEASURES: Radiographs were assessed by quality indicators pertinent to the clinical utility as acceptable or unacceptable. If erroneous by some indicator(s) but still contributing to the diagnostic information, a radiograph was rated as diagnostically acceptable. A score of quality points was calculated for each radiograph. RESULTS: The overall kappa statistics for intra-examiner reliability was 0.63, the proportional agreement 83%. For inter-examiner reliability, 0.42 and 71%, respectively. Although the evaluation criteria took the clinical utility of the radiographs into consideration, only 15% of bite-wings, 13% of periapicals, and 2% of panoramics received the maximum quality points. Erroneous film positioning was the most common fault on intraoral radiographs. On panoramics, the most frequent faults were in density and contrast and in patient positioning. The radiological evaluation had only been recorded for less than one fifth of the films. CONCLUSIONS: A proportion of radiographs fell short of the ideal. There is room for improvement in the quality of radiography in order to obtain the greatest possible diagnostic yield from the exposed radiographs.

Adult↗

Cultivated H-RS cells are resistant to CD95L-mediated apoptosis despite expression of wild-type CD95.

OBJECTIVE: In most cases of classic Hodgkin's disease (HD), Hodgkin and Reed-Sternberg (H-RS) cells clonally derive from germinal-center B cells. Within their rearranged immunoglobulin genes, somatic mutations rendering potentially functional immunoglobulin gene rearrangements nonfunctional were detected, indicating that H-RS cells do not express a B-cell receptor. Under physiologic conditions, these cells would undergo apoptosis within the germinal center. However, H-RS cells clonally expand, disseminate, and lead to clonal relapse of HD, indicating their resistance to induced programmed cell death. The underlying mechanism remains to be elucidated. MATERIALS AND METHODS: [corrected] Analysis of receptor-ligand interactions in primary H-RS cells is difficult to perform due to their scarcity in vivo and their low proliferation rate in vitro. Therefore, two [corrected] B-cellular H-RS cell lines (L1236 and L428) were used to test for the expression of CD95 by flow cytometry and for the induction of apoptosis after incubation with CD95L obtained from retrovirally transduced murine myoblasts. Sequence analysis of CD95 cDNA obtained from these H-RS cell lines was performed. RESULTS: Expression of CD95 on the cell surface was detected in both cell lines. However, after incubation with CD95L, the cells did not undergo apoptosis. To test whether mutations within the CD95 cDNA sequence caused resistance to apoptosis in H-RS cells, sequence analysis of CD95 cDNA obtained from L1236 and L428 was performed. In both cell lines, CD95 was not affected by somatic mutations. CONCLUSIONS: Our results indicate that the two H-RS cell lines L1236 and L428 are resistant to CD95-mediated apoptosis induced via CD95L, although wild-type CD95 is expressed. For further characterization of the mechanisms leading to prevention of apoptotic cell death in H-RS cells, it is necessary to determine impairments within the signaling cascade following CD95 activation.

Apoptosis↗

Radiographic periodontal attachment loss as an indicator of death risk in the elderly.

OBJECTIVES: Oral infections have been associated with serious systemic diseases and an increased risk of death. Our aims were to investigate whether radiographically-observed apical periodontitis lesions, carious teeth, periodontal attachment loss (horizontal bone loss, furcation lesions, number of teeth with infrabony periodontal pockets, the extent of infrabony periodontal pockets) and the sum of all these findings have any relationships with all-cause mortality within 4-year follow-up. MATERIAL AND METHODS: 292 community-dwelling elderly persons aged 76, 81 and 86 years. The number of deaths within 4 years was 54 (18.5%). In the dentate 169 subjects, of whom 32 (18.9%) deceased within 4 years, the mean number of teeth was 15.5 in men and 13.2 in women. The imaging method used was panoramic radiography supplemented by intraoral radiographs. RESULTS: 51% of the dentate subjects had infrabony pockets (mean 1.5, s.d. 2.2), and 40% had periapical periodontitis lesions (mean 1.0, s.d. 1.6). After controlling for age and gender, vertical bone loss judged as advanced infrabony pockets was associated with 4-year all-cause mortality (Odds ratio 2.2,1.0-4.7). Other associations were statistically insignificant. CONCLUSION: Periodontal attachment loss may indicate an increased risk of death in the elderly.

Aged↗

The Prevotella intermedia group organisms in young children and their mothers as related to maternal periodontal status.

Currently, the Prevotella intermedia group includes three biochemically and phylogenetically related species: Prevotella intermedia, Prevotella nigrescens, and the newly described Prevotella pallens. The two first-named species are mentioned with varying emphasis in connection with periodontal diseases, while such a connection of P. pallens is not known. Mothers serve as a plausible source of bacteria to their children, and conceivably, a mother with periodontitis as a recurrent reservoir of periodontally infecting organisms. In the present study, 23 mothers and their young children were examined for the presence of the P. intermedia group organisms in relation to maternal periodontal status (I: periodontal health, II: initial periodontitis, and III: advanced periodontitis). Species differentiation was based on established biochemical methods, electrophoretic mobility patterns, SDS-PAGE, and DNA hybridization. P. intermedia was not recovered from children but nearly exclusively from mothers in group III, thus confirming its association with periodontitis. P. nigrescens and P. pallens were frequently found in mothers and children. To determine bacterial transmission between a mother and her child, 72 isolates from 13 mother-child pairs were analyzed by arbitrarily primed PCR (AP-PCR). Similar AP-PCR types of P. nigrescens and/or P. pallens were recovered from 3/4 pairs in group I, 2/5 pairs in group II, and none in group III. Our results indicate that different species within the P. intermedia group have a different colonization pattern in childhood and that the periodontal status reflects qualitatively their presence in maternal saliva. Intra-familial transmission of P. nigrescens and P. pallens can occur in early childhood, however similar AP-PCR types were most obvious within periodontally healthy mother-child pairs.

Adult↗