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J Wolf

Publications and source records attributed to J Wolf.

At least 55 records · Page 3Linked to original sources
PubMed2001

An unprecedented type of migratory insertion reactions of unsaturated C3 units into Rh-O and Rh-C bonds.

A series of iodo- and hydroxorhodium(I) complexes of the general composition trans-[RhX(=C=C=CRR')(PiPr3)2] (X = I: 5-7; X = OH: 8-11) was prepared from the related chlororhodium(I) precursors. The hydroxo compounds behave as organometallic Brønsted bases and react with acids like MeCO2H, PhCO2H, PhOH, or TsOH by elimination of water to give the substitution products trans-[RhX'(=C=C=CRR')(PiPr3)2] (X' = MeCO2: 12, 13; X' = PhCO2: 14; X' = PhO: 15, 16; X' = TsO: 17, 18) in good to excellent yields. In contrast to the tosylates 17, 18, which react with CO by cleavage of the allenylidene-metal bond to give trans-[Rh(OTs)(CO)(PiPr3)2] (19), treatment of the acetato and phenolato derivatives 12, 13 and 15, 16 with CO affords by migratory insertion of the allenylidene unit into the Rh-O bond the alkynyl complexes trans-[Rh[C(triple bond)CCR(R')X'](CO)(PiPr3)2] (X' = MeCO2: 20, 21; X' = OPh: 22, 23). Similarly, the reactions of the hydroxo compounds 8, 10, and 11 with CH2(CN)2 and either CO or CNMe yield the carbonyl and the isocyanide complexes trans-[Rh[C(triple bond)CCR(R')CH(CN)2](L')(PiPr3)2] (L' = CO: 25-27; L' = CNMe: 28-30), respectively. By protolytic cleavage of the Rh-C sigma bond the gamma-functionalized alkynes HC(triple bond)CCR(R')CH(CN)2 (31, 32) are generated from 25, 26 and HCl in benzene. The molecular structure of 22 was determined by X-ray crystallography.

Journal Article↗
PubMed2001

Resistance to CD95-mediated apoptosis in breast cancer is not due to somatic mutation of the CD95 gene.

Resistance to CD95 (Apo-1/Fas)-mediated apoptosis is a typical feature of breast cancer cells. Recent studies identified deleterious mutations of the CD95 gene not only in a variety of B cell lymphomas but also in a number of solid tumor entities. Therefore, we amplified and sequenced selected regions of the CD95 gene from 48 breast cancer cases and 10 cell lines but no mutation was found. In the presence of both polymorphic alleles, loss of heterozygosity was excluded in 27 informative cases. We conclude, that relevant somatic mutations of the CD95 gene occur, if at all, at a low frequency and are not the primary cause for resistance to CD95-mediated apoptosis in breast cancer.

Apoptosis↗
PubMed2001

Oct-2 and Bob-1 deficiency in Hodgkin and Reed Sternberg cells.

Hodgkin and Reed Sternberg (H-RS) cells represent the malignant cells in classical Hodgkin's disease. Although derived from germinal center B cells, they do not express surface immunoglobulin. This has been explained by the presence of crippling mutations within the immunoglobulin genes in numerous cases of Hodgkin's disease. As immunoglobulin gene expression in B cells requires an interaction between octamer sites and the transactivating factors Oct-2 and Bob-1, this study addresses the expression of the transcription factors Oct-2 and Bob-1 in H-RS cells. In Hodgkin's disease-derived cell lines, low levels of Oct-2 transcripts but no Oct-2 protein were detected. Transcripts of Bob-1, a B-cell-specific co-factor of Oct-2, could not be observed in these cell lines. Absence of Oct-2 and Bob-1 protein expression in primary H-RS cells was demonstrated by performing immunohistochemistry in 20 cases of classical Hodgkin's disease. H-RS cells stained negative for both proteins in all of the cases analyzed. In conclusion, absence of functional Oct-2 and Bob-1 cells represents a novel mechanism for immunoglobulin gene deregulation in H-RS cells. Lack of Oct-2 and Bob-1 points to a defect in transcription machinery in H-RS cells and is associated with lack of immunoglobulin gene expression in these cells.

3T3 Cells↗
PubMed2001

Locoregional treatment of low-grade B-cell lymphoma with CD3xCD19 bispecific antibodies and CD28 costimulation. I. Clinical phase I evaluation.

We describe the first clinical application of T-cell-recruiting bispecific antibodies directly into the tumor without the need to preactivate the effector cells. In a Phase I clinical trial, 10 patients with low-grade B-cell lymphoma were treated by a single locoregional injection of CD3xCD19 bispecific antibodies. Costimulatory signaling, which is required for the optimal activation of resting T cells, was provided by the simultaneous administration of CD28 antibodies. Equal amounts of both antibodies were injected together at 4 different dose levels (30 microg: 3 patients; 270 microg: 3 patients; 810 microg: 3 patients; 1,600 microg: 1 patient). The injection was well tolerated with mild to moderate adverse effects (2/10 patients) consisting of erythema and fever at the third dose level. The maximum tolerated dose was not reached at 810 microg of injected antibodies. Three patients showed a serum peak of TNFalpha on day 2 or 3 after the antibody application, reflecting rather an activation of CD4-positive T cells than an FcR-mediated effect. Five patients developed anti-mouse antibodies after injection of the murine immunoglobulins. Nine patients were evaluable for restaging examinations 6 weeks after the antibody application, with 2 of them (22%) showing a local clinical response. We found that a single locoregional injection of CD3xCD19+CD28 antibodies is feasible up to a dose of at least 1,600 microg of each antibody. However, the development of human anti-mouse antibodies points toward the requirement for new formats of bispecific proteins with reduced immunogenicity.

Aged↗
PubMed2001

Loss of heterozygosity in the Hodgkin-Reed Sternberg cell line L1236.

Hodgkin-Reed Sternberg cells are derived from germinal centre B-cells in most cases. Somatic mutations affecting their rearranged immunoglobulin genes were detected, rendering potential functional rearrangements non-functional. Under physiological conditions such cells would be designated to undergo apoptosis within the germinal centre. In search for the specific transforming event that prevents Hodgkin-Reed Sternberg cells from programmed cell death, cytogenetic analyses were broadly performed but did not reveal specific chromosomal aberrations. Analysis of these cells on the molecular level is difficult to perform due to the scarcity of the cells in the lymphoma tissue and the given limitations of in situ studies. To overcome these limitations, the cell line L1236, known to be derived from Hodgkin-Reed Sternberg cells in situ, was chosen for allelotype analysis. Using a panel of microsatellite loci assigned to nearly all chromosomal arms, regions of loss of heterozygosity were detected on chromosomal arms 6p, 9q and 17p. The size of lost segments was estimated by amplification of additional microsatellite loci mapped to the respective regions. Further analyses of single Hodgkin-Reed Sternberg cells will reveal whether LOH affecting these regions is a recurrent event in HD and to which extent the smallest commonly affected region can be estimated.

Alleles↗
PubMed2001

Cell fusion is not involved in the generation of giant cells in the Hodgkin-Reed Sternberg cell line L1236.

The mechanism of multinucleated cell formation in Hodgkin's disease has not yet been elucidated. We asked whether the giant multinucleated cells of the H-RS cell line L1236 develop via fusion of the predominant smaller cells. As a positive control for the fusion assay, human B cells from the B-cell lymphoma cell line BJA-B were split into two fractions, stained with the fluorochromes CMTMR and CMFDA, respectively, and fused using the polyethylene glycol 1500 cell hybridization protocol. Double-stained cells indicating fusion of BJA-B cells were detectable for up to 5 days. In parallel, L1236 cells were split into two fractions, stained with the fluorochromes, and mixed. No double-stained L1236 cells were detected. The same result was obtained when using FACS-sorted small mononuclear L1236 cells. It is thus concluded that the large multinucleated cells of the monoclonal H-RS cell line L1236 have emerged by endomitosis rather than by spontaneous cell fusion.

Cell Culture Techniques↗
PubMed2001

Hodgkin disease-derived cell lines expressing ubiquitous mitochondrial creatine kinase show growth inhibition by cyclocreatine treatment independent of apoptosis.

Ubiquitous mitochondrial creatine kinase (uMtCK), a key enzyme in energy metabolism, was identified by differential display PCR to be specifically overexpressed in L1236, the first cell line of definite Hodgkin origin. RT-PCR confirmed overexpression of uMtCK in the L1236 cell line and the absence of cytosolic B-CK, which is co-expressed with MtCK physiologically. Cyclocreatine (cCr), whose phosphorylated form is a very poor substrate for CK, inhibited proliferation of the L1236 cell line nearly entirely. This inhibition by cCr was partially reversed by competition with creatine, which by itself had no effect on proliferation of the L1236 cell line. Although these results support a role of CK activity in the inhibitory action of cCr, it remains open whether the cCr effect is due to its inhibition of CK-linked energy metabolism or if alternative mechanisms have to be considered. Because the anti-proliferative effect of cCr was not due to induction of apoptosis, in contrast to most other anticancer agents, treatment with the creatine analogue cCr may represent an advantageous therapeutic approach for cells resistant to programmed cell death.

Antineoplastic Agents↗
PubMed2001

Changes in subjective quality of life among homeless adults who obtain housing: a prospective examination.

BACKGROUND: The aim of this present study is to examine whether overall subjective quality of life and specific domains of quality of life change among homeless adults after they become housed, and if so, what factors predict changes in satisfaction. METHODS: The data analysed here were collected through face-to-face interviews with a sample of 485 homeless adults who were interviewed as often as bi-monthly over a 16-month period. Bivariate analyses examined initial differences between three groups: homeless people who did not exit from homelessness; those with an exit from homelessness to dependent housing; and those with an exit to independent housing. Bivariate analyses also examined differences in subjective quality of life before and after an exit from homelessness among the three groups. Multivariate analyses identified predictors of changes in quality of life before and after exit. RESULTS: This study has three main findings. First, homeless people who obtained independent housing had the largest positive and significant improvements in satisfaction with overall quality of life, and in satisfaction with housing, leisure and money. Second, becoming housed was not a predictor of changes in overall quality of life perceived by homeless people, nor in their satisfaction with leisure, clothing, food, and social life. Furthermore, a positive change in housing satisfaction was not associated with all types of exits from homelessness; only a move into independent housing predicted such a change, but a move into dependent housing did not. Finally, of all the covariates included as predictors at baseline, only two variables seemed to consistently predict changes in satisfaction; namely, self-assessed general health and self-assessed self-help skills. CONCLUSIONS: This study suggested that becoming independently housed may improve some aspects of quality of life for homeless people, but not others. The results suggest that homeless people prefer to be independently housed relative to remaining homeless or staying in a dependent housing situation, but that independent housing does not necessarily improve other aspects of their lives.

Adult↗
PubMed2001

The influence of suspended particles on the acute toxicity of 2-chloro-4-nitro-aniline, cadmium, and pentachlorophenol on the valve movement response of the zebra mussel (Dreissena polymorpha).

The Dreissena-Monitor is a biological early warning system for the continuous monitoring of river water quality, based on the valve movements of two groups of 42 zebra mussels (Dreissena polymorpha). Laboratory experiments with Cd, PCP, and 2-chloro-4-nitro-aniline were conducted in combination with suspended particles (a mixture of stinging nettle powder, bentonite, and quartz powder). An increase of suspended particles up to a nominal concentration of 540 mg/L within 5 min did not evoke any reactions by the mussels significantly different from normal. The distribution between water and solids was analyzed for Cd and 2-chloro-4-nitroaniline, with the result that the former quickly adsorbed to the particles, whereas the latter did not bind to the particles at all. The behavior of the zebra mussels revealed that the detection of 2-chloro-4-nitro-aniline was not affected by the presence of suspended matter. In the cases of Cd and PCP, D. polymorpha was able to detect these substances when they were particle-associated at least as well or better as when they were dissolved in the water. The results are discussed with respect to the physiology of the organisms and the bioavailability of toxicants, as well as to the consequences these results may have under field conditions.

Adsorption↗
PubMed2001

Carcinogenicity assays of wood dust and wood additives in rats exposed by long-term inhalation.

OBJECTIVE: This study evaluates whether wood dust and/or wood preservatives develop a carcinogenic potential against the tissues of the airways of rats. METHODS: The formation of tumors of the respiratory tract after exposure to wood dust was studied in six groups of approximately 60 female Fischer 344 rats exposed by long-term inhalation to mean concentrations of (1) 18 mg/m3 of untreated oak wood dust, (2) wood preservatives containing ca. 1 microgram/m3 lindane and 0.2 microgram/m3 of pentachlorophenol (PCP) in the exposure air, or lindane and 18 micrograms/m3 of PCP (group lindane/PCP vapors, and group oak wood treated with lindane/PCP), (3) 21 or 39 micrograms/m3 of sodium dichromate (calculated as CrO3, group chromate aerosol and group oak wood with chromate), and 72 micrograms/m3 of N-nitrosodimethylamine vapors as positive control. The negative control group consisted of 115 animals (sham-exposed). RESULTS: Tumors of the nasal cavity developed in two rats exposed to chromate aerosol or in combination with wood dust (2/102, 2%). Malignant tumors of the lower respiratory tract were induced only in exposed groups of rats (three adenocarcinomas of the lung and four bronchiolar lung carcinomas, 7/254, 2.8%). More respiratory tract tumors were observed in rats exposed to chromate or wood with chromate (5/102, 5%), also in groups exposed to oak wood dust (oak untreated, oak + chromate, oak + lindane/PCP; together 5/155, 3.2%). Analysis of 'unpreserved' oak wood dust revealed up to 5 micrograms/m3 of chromate. When this exposure was taken into account, eight of nine animals with respiratory tract tumors (including nasal cavity) had exposure to chromate, while only one tumor occurred in the group lindane/PCP. Otherwise the incidence of systemic tumors was increased in animals exposed to lindane/PCP, due in particular to a significantly increased incidence of liver tumors (OR = 3.7; 1.24-11.3; P = 0.019). Fatal (mucoepidermoid) tumors were induced by N-nitrosodimethylamine (NDMA) in the positive control (14/46, 30%). No such tumors of the respiratory tract were observed in the negative control. CONCLUSIONS: Tumors in the respiratory tract were found only in exposed animals, predominantly in the groups which inhaled oak wood dust and chromate stain. Chromate may play a decisive role for the etiology of tumors of the nasal cavity in wood workers. This assumption should be supported by further dose-response studies.

Air Pollutants↗
PubMed2001

No evidence for a different magnitude of the time factor for continuously fractionated irradiation and protocols including gaps in two human squamous cell carcinoma in nude mice.

BACKGROUND AND PURPOSE: To study whether the magnitude of the time factor is different for continuously fractionated irradiation and for fractionation protocols including gaps. MATERIALS AND METHODS: Two human head and neck squamous cell carcinomas (SCCs), FaDu and GL, were transplanted subcutaneously into the right hindleg of NMRI (nu/nu) mice and irradiated with 30 fractions under ambient conditions within 2, 6 and 10 weeks. Irradiations within 6 and 10 weeks were given either as a continuous course or with a mid-course gap of 3 weeks. The end-point of the experiments was local tumor control at day 120 (FaDu) or day 180 (GL) after the end of treatment. RESULTS: In FaDu tumors, two experimental cohorts (A, B) yielded significantly different results and were analyzed separately. In cohort A, the tumor control dose 50% (TCD50) increased from 37 to 89 Gy when the treatment time of continuous fractionated irradiation was extended from 2 to 10 weeks. The recovered dose/day (D(r)) was 0.98 Gy (95% confidence interval, 0.72; 1.27). In cohort B, the TCD50 increased from 35 to 63 Gy, and the D(r) was 0.51 Gy (0.24; 0.75). In GL tumors, the TCD50 for continuously fractionated irradiation increased from 41 to 48 Gy. This increase was not significant, and the D(r) was 0.15 Gy (0; 0.30). None of the TCD50 and D(r) values obtained in both tumor models for continuous irradiation vs. irradiation with a gap were significantly different. CONCLUSIONS: Prolongation of the overall treatment time of fractionated irradiation resulted in a pronounced decrease of local control in human FaDu SCC and little decrease of local control in human GL SCC. No evidence was found that the magnitude of the time factor in these tumors is different for continuous fractionation or fractionation protocols including gaps.

Animals↗
PubMed2001

Male gonadal dysfunction in patients with Hodgkin's disease prior to treatment.

UNLABELLED: Infertility after treatment of patients with Hodgkin's disease (HD) is considered as a side effect of alkylating agent containing chemotherapy regimens. To investigate whether gonadal failure is related primarily to the toxic effect of chemotherapy or rather to the disease itself, we investigated the fertility status before the onset of treatment. PATIENTS AND METHODS: Semen quality and hormonal status were evaluated in 158 patients with first diagnosis of HD enrolled into trials of the German Hodgkin Lymphoma Study Group (GHSG). The median age of the patients was 28 years (range 16-52). Twenty patients (13%) were classified as early stage HD, 63 patients (40%) as intermediate stage, and 75 patients (47%)) as advanced stage according GHSG grading. Sixty-seven patients (42%) showed systemic symptoms. Semen analysis was performed according to WHO guidelines. Follicle-stimulating hormone (FSH) and luteinising hormone (LH) plasma levels were measured by specific double-antibody radio-immune-assay (RIA) methods. RESULTS: Prior to treatment, severe damage of fertility, i.e.. azoospermia and oligoasthenoteratospermia (OAT-syndrome) was found in 13 (8%) and 20 patients (13%), respectively. Thirty-eight patients (24%) had single, i.e., oligo-(O), astheno-(A) or teratospermia-(T), and 40 patients (26%) showed combined damages, i.e., OA, OT or AT. In 47 patients (30%) a normal sperm count was found. Thus, III patients (70%) showed semen abnormalities before the onset of treatment. In a multivariate analysis elevated ESR (P < 0.003) and advanced stage of disease (P < 0.01) could be distinguished as prognostic factors for severe damage of fertility. No correlation was found between pre-therapeutic gonadotropine levels and fertility status. CONCLUSION: Patients with HD have an increased risk for inadequate semen quality even prior to treatment. Infertility is more frequent in patients with elevated ESR and advanced stage of disease. This association demonstrates the predominant influence of the disease on fertility. Assuming HD is the major initial cause for infertility efforts should be made to identify new non-gonadal toxic chemotherapies to be able to regain fertility after effective therapy. Further investigations have to be performed to clarify mechanisms inducing fertility defects in patients with HD.

Adolescent↗
PubMed2001

Class switch recombination was specifically targeted to immunoglobulin (Ig)G4 or IgA in Hodgkin's disease-derived cell lines.

In T cell-dependent immune responses, class switch recombination occurs in germinal centres. There is now evidence that Hodgkin/Reed-Sternberg cells are derived from germinal centre B cells. Cytokines specifically determine the direction of class switching, i.e the isotype of the new antibodies. We performed restriction analyses and polymerase chain reaction on the immunoglobulin heavy chain loci for five Hodgkin's disease-derived B-cell lines and one Hodgkin's disease-derived T-cell line in order to analyse class switch recombination. In all the B-cell lines, class switch recombination had been targeted to Calpha4 or Calpha1/2. This showed that cell-line precursors had undergone class switching, probably under the influence of TH2 or TH3 cell-derived cytokines. Deletions comprising several constant region genes were observed in cell lines L428, L1236, L591 and KMH2. Karyotype analyses of two of these revealed translocational breakpoints within the immunoglobulin heavy chain gene locus. Our data support the view that a chromosomal instability may occur during class switch recombination in Hodgkin/Reed-Sternberg cells causing chromosomal breaks. Thus, as in other germinal centre B cell-derived lymphomas, the immunoglobulin gene locus may be frequently involved in structural chromosomal aberrations in Hodgkin's disease.

Blotting, Southern↗
PubMed2001

Deregulation of immunoglobulin gene transcription in the Hodgkin-Reed Sternberg cell line L1236.

Hodgkin-Reed Sternberg (H-RS) cells harbour clonal immunoglobulin gene (Ig) rearrangements in almost all cases of classical Hodgkin's disease but lack Ig gene expression. In the H-RS cell line L1236, a somatic mutation of the Ig heavy-chain gene promoter octamer motif has been described as a putative reason for absence of Ig gene expression. We addressed transcriptional activity of this mutated promoter by performing reporter gene studies and gel retardation assays. The results showed that the mutation outside the coding region of the rearranged Ig gene in L1236 cells leads to downregulation of Ig gene expression in H-RS cells.

Gene Rearrangement↗
PubMed2001

Dental diseases and loss of teeth in a group of Finnish alcoholics: a radiological study.

A total of 85 Finnish alcohol-dependent subjects and 53 controls were studied with panoramic radiography. The aim was to study the possible associations between prolonged alcohol consumption and dental health. The mean number of teeth, caries lesions, endodontic treatments, periapical lesions, marginal bone loss, and periodontal infrabony pockets was studied. The subjects met the diagnostic criteria of alcohol dependence as set out in DSM-IV and ICD-10. The control group comprised social drinking volunteers with an AUDIT score < or =8. For the final results the subjects were divided into groups on the basis of sex and age. The social backgrounds of the subjects were similar, except for employment and smoking. The results show significantly fewer teeth and more caries in the alcoholic group. There was a tendency for the alcoholics <45 years of age to have more endodontically treated teeth than the controls, but no difference in the number of periapical lesions in endodontically treated teeth was found. Horizontal bone loss and the presence of calculus were more frequent in alcoholic men than in alcoholic women. Significantly more horizontal bone loss was observed in the group of alcoholic nonsmokers than in nonalcoholic nonsmokers. In the nonsmoking groups alcoholics had significantly more periodontal destruction than the nonsmoking controls. We conclude that radiological dental health among individuals dependent on alcohol is weakened by more caries, more horizontal bone loss, and more numerous vertical infrabony pockets than social drinkers.

Adult↗
PubMed2001

Establishing process indicators for joint working in mental health: rationale and results from a national survey.

Effective joint working in mental health is a national concern as indicated by a series of governmental directives and initiatives aimed at improving practice in this area. Joint working is fundamental to the successful implementation of 'community care'. Many people, particularly the public, equate the introduction of the Community Care Act (Department of Health, 1990), with the beginning of community care as a social policy. In reality, however, community care has a much longer history in the UK involving the shift in the 1950s from providing care in the hospital to providing care in the community. Thus, one of the most obvious reasons for this concern expressed in the media and felt by the public is that 'community care' isn't working. While this is an important consideration, it is not the only explanation as to why joint working has come to occupy such a prominent position in the minds of health strategists and politicians. This paper explores our concern with joint working in mental health and proposes one way in which joint working can be effectively monitored and measured.

Community Mental Health Services↗
PubMed2001

Safety and efficacy of short-duration oral terbinafine for the treatment of tinea corporis or tinea cruris in subjects with HIV infection or diabetes.

Cutaneous fungal infections in immunocompromised patients can be aggressive and difficult to treat. To determine the safety and efficacy of oral terbinafine for the treatment of tinea corporis or tinea cruris in subjects with human immunodeficiency virus (HIV) infection or diabetes, 2 prospective, randomized, open-label studies were conducted in general community and referral centers. HIV-positive (n = 6) and diabetic patients (n = 8) between the ages of 18 and 75 years diagnosed with either tinea corporis or tinea cruris, as confirmed by potassium hydroxide (KOH) wet mount microscopy, were randomized to receive either 1 or 2 weeks of the antifungal treatment. Patients received oral terbinafine 250 mg once daily for 1 or 2 weeks. Main outcome measures were mycological cure, determined at week 6 for HIV-positive and diabetic patients. Three subjects were excluded from the efficacy analyses because of negative cultures at screening (n = 2) and lack of follow-up cultures (n = 1). Efficacy results were similar between the 1- and 2-week groups in both studies. All HIV-positive subjects and 83% of diabetic subjects achieved mycological cures at week 6 based on culture results. In a safety population that included all randomized patients (N = 14), no subject experienced adverse events or significant changes in laboratory findings related to study medication. Results of these small series indicate that a short course of oral terbinafine 250 mg once daily is a safe and effective treatment for tinea corporis or tinea cruris in subjects with HIV infection or diabetes.

AIDS-Related Opportunistic Infections↗