Biomedical subjects

J Wolff

Publications and source records attributed to J Wolff.

At least 37 records · Page 2Linked to original sources

PubMed2002

Unrelated donor BMT recipients given pretransplant low-dose antithymocyte globulin have outcomes equivalent to matched sibling BMT: a matched pair analysis.

Fifty-seven patients receiving unrelated donor (UD) BMT were matched for disease and stage with 57 recipients of genotypically matched related donor (MRD) BMT. All UD recipients were matched serologically for A and B and by high resolution for DR and DQ antigens. All patients received CsA and 'short course' methotrexate with folinic acid. Unrelated donor BMT patients also received thymoglobulin 4.5 mg/kg (6 mg/kg if <30 kg) in divided doses over 3 days pretransplant. For UD and RD BMT, respectively, incidence of acute GVHD grade II-IV was 19 +/- 6% vs 36 +/- 8%, grade III-IV 10 +/- 6% vs 18 +/- 7%, chronic GVHD 44 +/- 8% vs 51 +/- 8%, non-relapse mortality 15 +/- 5% vs 8 +/- 4% at 100 days, 28 +/- 8% vs 36 +/- 7% at 3 years. At 3 years, relapse was 45 +/- 7% vs 42 +/- 7%, and disease-free survival 39 +/- 7% vs 37 +/- 7%. None of these differences are significant. Three-year overall survival was identical at 42 +/- 7%. For 29 patients with low/intermediate risk leukemia, disease-free survival was 68 +/- 10% after UD BMT vs 59 +/- 9% for RD BMT recipients (P = NS). Corresponding figures for high risk patients were 14 +/- 7% and 21 +/- 8%, respectively. We conclude that UD BMT recipients matched as above and given pretransplant ATG have similar outcomes to recipients of MRD BMT using conventional drug prophylaxis. Unrelated donor BMT should be considered in any circumstance where MRD BMT is routine.

Antilymphocyte Serum↗

PubMed2002

Storage of blood for in vitro generation of dendritic cells.

BACKGROUND: Since the development of techniques to cultivate DC from peripheral blood, there has been a great deal of interest in the use of these cells in immunotherapeutic strategies. In a clinical setting, delays often occur between when blood is drawn and when it is processed. We therefore investigated the effect of overnight storage on the yield, morphology and phenotype of DC cultured from the peripheral blood of healthy volunteers. METHOD: Blood was processed either immediately, or after storage for 24 h in the fridge (4 degrees C) or at room temperature (RT, 20 degrees C). Samples were compared for starting cell number, DC yield and characteristics (morphology and phenotype). RESULTS: The number of PBMC that could be obtained was significantly lower from the refrigerated samples compared with both the freshly processed sample and that stored at RT. Samples processed after overnight storage at RT yielded cells morphologically identical to DC cultured from freshly processed samples. Only when samples were both stored and processed cold did the cultured cells not have typical DC morphology. DC cultured from the refrigerated samples showed a significant reduction in MHC II expression compared with samples processed fresh or stored at RT. This expression increased slightly when the sample was first warmed. Total DC yield and the percentage yield of cultured DC was not significantly different for any of the groups. DISCUSSION: We conclude that, if immediate processing of blood for in vitro generation of DC is not possible, samples should be stored at room temperature (approximately 20 degrees C).

Adult↗

PubMed2002

A miss for NIS?

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Animals↗

PubMed2001

Spatiotemporal addressing of surface activity.

We have modified surface catalytic activity in real time and space by focusing an addressable laser beam to differentially heat a platinum (110) single-crystal surface. Ellipsomicroscopy imaging of local conditions (such as reactant and product local coverages) enabled us to close the loop between sensing and actuation (both spatiotemporally resolved). Pulses and fronts, the basic building blocks of patterns, could be formed, accelerated, modified, guided, and destroyed at will. Real-time image processing and feedback allow the design and implementation of new classes of nonlocal evolution rules.

Journal Article↗

PubMed2001

Hereditary benign chorea: clinical and genetic features of a distinct disease.

OBJECTIVE: To describe a second family with benign hereditary chorea (BCH, OMIM 118700) and suggestive linkage to chromosome 14q. BCH is an autosomal dominant disorder of early onset that differs from Huntington disease in being nondementing and nonprogressive without other neurologic signs. There has been controversy regarding the existence of BCH as a discrete disorder. BACKGROUND: A single kindred was recently reported with linkage of BCH to a 20.6-KcM region on chromosome 14q. METHODS: In a four-generation family with BCH, linkage was evaluated to markers in a 23-KcM region between D14S49 and D14S66 that contains the putative BCH locus. RESULTS: A multipoint nonparametric lod score of 3.01 is consistent with linkage of disease in this family to the 14q BCH locus. A recombination event in one affected individual enabled the critical region to be narrowed to 6.93 KcM flanked by D14S1068 and D14S1064. This region contains two candidate genes: glial maturation factor beta and guanosine triphosphate cyclohydrolase 1 (GCH1). Survival motor neuron (SMN) interacting protein-1 is eliminated as a candidate gene because it lies outside the critical region. No sequence alteration was identified in the coding region of GCH1 in an affected individual. CONCLUSION: These data provide further evidence that BCH is a distinct entity, narrow the location of BCH to a 6.93-KcM region on chromosome 14q, and exclude SMN interacting protein-1 as a candidate gene.

Adolescent↗

PubMed2001

Plasma membrane localization of palmitoylated tubulin.

PC12 pheochromocytoma cells incorporate [(3)H]palmitic acid into tubulin in a time- and cell-density-dependent manner. The plasma membrane-enriched fraction contains most of the radioactivity of the membrane pellet. While palmitoylated tubulin is found in both the cytoplasm and particulate fraction, the bulk of [(3)H]palmitic acid bound to tubulin is present in the crude membrane pellet and the tubulin extracted from the plasma membrane is more heavily palmitoylated than that extracted from endoplasmic reticulum. Detergent-extracted tubulin from plasma membrane is, to a large extent, polymerization competent; a substantial fraction, increasing as a function of labeling time, is not hydroxylamine-labile. The requirement for detergent extraction, the accompanying changes in tubulin properties and the present findings of preferential incorporation of labeled tubulin into plasma membranes, make it clear that direct incorporation of tubulin into the plasma membrane can occur.

Animals↗

PubMed2001

Iodine nutrition and the risk from radioactive iodine: a workshop report in the chernobyl long-term follow-up study.

The major fallout of radionuclides from the nuclear power station accident at Chernobyl on 26 April, 1986, occurred in regions of Ukraine and Belarus that are believed to be moderately deficient in dietary iodine. On 17 November, 2000, in conjunction with the Ukraine-Belarus-USA study of developing thyroid disease in a cohort of individuals exposed as children, a workshop was held to review what is known about iodine nutrition in the region, how this might influence the risk of thyroid tumor formation from radioiodine, and whether and how iodine nutrition should be monitored in this long-term project. This report is a summary of the workshop proceedings. Although no precise information about iodine intake in 1986 was found, the prevalence of mild goiter in the region's children suggested iodine deficiency and urinary iodine measurements begun in 1990 indicated that mild to moderate deficiency existed. Increased thyroid iodine uptake and increased thyroid size in 1986 resulting from iodine deficiency would have had counteracting influence on the thyroid radiation dose and knowledge of these parameters is required for dose reconstruction. More problematic is the possible role of iodine deficiency in the years following the accident. Theoretically, the resulting increase in thyroid cellular activity might increase the risk of tumorigenesis but experimental or clinical evidence supporting this hypothesis is meager or absent. Despite this limitation it was considered important to monitor iodine nutrition in the cohort subjects in relation to their place of residence and over time. Methods to accomplish this were discussed.

Goiter↗

PubMed2001

Population pharmacokinetics and dynamics in phase II studies of the novel bioreductive alkylating cytotoxic indoloquinone EO9.

Population pharmacokinetic-dynamic analysis was prospectively integrated in the clinical phase II programme of EO9 to determine the population pharmacokinetic profile in a larger population of patients, to estimate individual patient pharmacokinetic parameters, and to investigate relationships between drug exposure and clinical outcome. A sparse sampling method was developed, which involved three sampling times, and was implemented during course 1. A Bayesian algorithm was used to estimate individual pharmacokinetic parameters, in particular total plasma clearance (CL) of EO9 and area under the curve (AUC). In total, samples were collected of 85 (65%) of the patients. Pharmacokinetic evaluation was successful in 61 (72%) of the sampled patients. CL of EO9 showed substantial variability (median 5.08 l/min; range 2.67-6.42) and was of the same magnitude as in the phase I study where full pharmacokinetic profiles were used. No significant relationships were noticed between exposure parameters and safety, but overall limited toxicity was observed. No tumor responses were documented. Prospective implementation of large-scale population pharmacokinetic-dynamic analysis is feasible and may generate important findings, in particular when tumor responses and relevant toxicity are observed.

Adult↗

PubMed2001

Physiology and pharmacology of iodized oil in goiter prophylaxis.

Thyroid complications resulting from excess iodide such as thyrotoxicosis, thyroiditis, sialadenitis, or hypothyroidism are much rarer after iodine supplementation with Lipiodol than with KI. They do not militate against its widespread use in endemic goiter populations, especially in pregnant women. However, patients with multinodular goiter should not be treated or should be treated only under careful observation. When Lipiodol-induced thyrotoxicosis occurs it tends to be mild or even subclinical and self-limited. If treatment is required, potassium perchlorate with or without thionamides is recommended. Iodide goiter has not been seen after Lipiodol supplementation, nor has thyroiditis. Sialadenitis occurs rarely. Iodide derived from Lipiodol readily enters the fetus, possibly by active transport, and theoretically endangers the fetus because autoregulation of the fetal thyroid occurs late during gestation. Despite the difficulty in distinguishing iodide goiter from iodide deficiency goiter of the newborn, no cases of neonatal iodide goiter have been reported. Possible mechanisms of thyroid inhibition by excess iodide are briefly discussed. The use of locally produced iodized plant oils is recommended for financial reasons as well as for the benefits derived from local participation.

Adult↗

PubMed2001

Erythropoietin in urologic oncology.

OBJECTIVES: The use of erythropoietin (EPO) for the treatment of anemia associated with urological malignancies is not well defined. The rate of anemia is dependent on the type of cancer and on the different types of treatment. Only with a substantial risk for blood transfusion is substitution treatment by EPO justified. Additionally, the long-term risks of blood transfusions have to be balanced against the costs of EPO treatment. METHODS: Different experts have reviewed the literature on anemia and EPO regarding the four main tumor entities. RESULTS/CONCLUSIONS: In prostate cancer, EPO treatment may be justified before radical prostatectomy and in patients with advanced, hormone-refractory disease. In bladder cancer, significant treatment-related anemia mainly occurs in patients who have to undergo radical cystectomy and in patients who will be treated with polychemotherapy for metastatic disease. Patients with renal cell carcinoma rarely suffer from anemia and thus are usually not candidates for EPO treatment. Testis cancer patients only have a substantial risk for blood transfusions if they belong to the intermediate or poor prognosis group according to IGCCCG or if they need salvage chemotherapy or salvage surgery. However, in testis cancer patients EPO treatment should generally be preferred to blood transfusions since cure rates are excellent and thus the potential risks of transfusion-related infections are significant.

Anemia↗

PubMed2001

Familial dyskinesia and facial myokymia (FDFM): a novel movement disorder.

We describe here familial dyskinesia and facial myokymia (FDFM), a novel autosomal dominant disorder characterized by adventitious movements that sometimes appear choreiform and that are associated with perioral and periorbital myokymia. We report a 5-generation family with 18 affected members (10 males and 8 females) with FDFM. The disorder has an early childhood or adolescent onset. The involuntary movements are paroxysmal at early ages, increase in frequency and severity, and may become constant in the third decade. Thereafter, there is no further deterioration, and there may even be improvement in old age. The adventitious movements are worsened by anxiety but not by voluntary movement, startle, caffeine, or alcohol. The disease is socially disabling, but there is no intellectual impairment or decrease in lifespan. A candidate gene and haplotype analysis was performed in 9 affected and 3 unaffected members from 3 generations of this family using primers for polymorphic loci closely flanking or within genes of interest. We excluded linkage to 11 regions containing genes associated with chorea and myokymia: 1) the Huntington disease gene on chromosome 4p; 2) the paroxysmal dystonic choreoathetosis gene at 2q34; 3) the dentatorubral-pallidoluysian atrophy gene at 12p13; 4) the choreoathetosis/spasticity disease locus on 1p that lies in a region containing a cluster of potassium (K+) channel genes; 5) the episodic ataxia type 1 (EA1) locus on 12p that contains the KCNA1 gene and two other voltage-gated K+ channel genes, KCNA5 and KCNA6; 6) the chorea-acanthocytosis locus on 9q21; 7) the Huntington-like syndrome on 20p; 8) the paroxysmal kinesigenic dyskinesia locus on 16p11.2-q11.2; 9) the benign hereditary chorea locus on 14q; 10) the SCA type 5 locus on chromosome 11; and 11) the chromosome 19 region that contains several ion channels and the CACNA1A gene, a brain-specific P/Q-type calcium channel gene associated with ataxia and hemiplegic migraine. Our results provide further evidence of genetic heterogeneity in autosomal dominant movement disorders and suggest that a novel gene underlies this new condition.

Adolescent↗

PubMed2000

Mapping of a syndrome of X-linked thrombocytopenia with Thalassemia to band Xp11-12: further evidence of genetic heterogeneity of X-linked thrombocytopenia.

X-linked thrombocytopenia with thalassemia (XLTT; Online Mendelian Inheritance in Man [OMIM] accession number 314050) is a rare disorder characterized by thrombocytopenia, platelet dysfunction, splenomegaly, reticulocytosis, and unbalanced hemoglobin chain synthesis. In a 4-generation family, the gene responsible for XLTT was mapped to the X chromosome, short arm, bands 11-12 (band Xp11-12). The maximum lod score possible in this family, 2.39, was obtained for markers DXS8054 and DXS1003, at a recombination fraction of 0. Recombination events observed for XLTT and markers DXS8080 and DXS8023 or DXS991 define a critical region that is less than or equal to 7.65 KcM and contains the gene responsible for the Wiskott-Aldrich syndrome (WAS; OMIM accession number 301000) and its allelic variant X-linked thrombocytopenia (XLT; OMIM accession number 313900). Manifestations of WAS include thrombocytopenia, eczema, and immunodeficiency. In WAS/XLT the platelets are usually small, and bleeding is proportional to the degree of thrombocytopenia. In contrast, in XLTT the platelet morphology is normal, and the bleeding time is disproportionately prolonged. In this study no alteration in the WAS gene was detected by Northern blot or Western blot analysis, flow cytometry, or complimentary DNA dideoxynucleotide fingerprinting or sequencing. As has been reported for WAS and some cases of XLT, almost total inactivation of the XLTT gene-bearing X chromosome was observed in granulocytes and peripheral blood mononuclear cells from 1 asymptomatic obligate carrier. The XLTT carrier previously found to have an elevated alpha:beta hemoglobin chain ratio had a skewed, but not clonal, X-inactivation pattern favoring activity of the abnormal allele. Clinical differences and results of the mutation analyses make it very unlikely that XLTT is another allelic variant of WAS/XLT and strongly suggest that X-linked thrombocytopenia mapping to band Xp11-12 is a genetically heterogeneous disorder.

Blotting, Northern↗

PubMed2000

Deoxyhypusine synthase generates and uses bound NADH in a transient hydride transfer mechanism.

Deoxyhypusine is a modified lysine residue. It is formed posttranslationally in the precursor of eukaryotic initiation factor 5A (eIF5A) by deoxyhypusine synthase, employing spermidine as a butylamine donor. In the initial step of this reaction, deoxyhypusine synthase catalyzes the production of NADH through dehydrogenation of spermidine. Fluorescence measurements of this reaction revealed a -22-nm blue shift in the emission peak of NADH and a approximately 15-fold increase in peak intensity, characteristics of tightly bound NADH that were not seen by simply mixing NADH and enzyme. The fluorescent properties of the bound NADH can be ascribed to a hydrophobic environment and a rigidly held, open conformation of NADH, features in accord with the known crystal structure of the enzyme. Considerable fluorescence resonance energy transfer from tryptophan 327 in the active site to the dihydronicotinamide ring of NADH was seen. Upon addition of the eIF5A precursor, utilization of the enzyme-bound NADH for reduction of the eIF5A-imine intermediate to deoxyhypusine was reflected by a rapid decrease in the NADH fluorescence, indicating a transient hydride transfer mechanism as an integral part of the reaction. The number of NADH molecules bound approached four/enzyme tetramer; not all of the bound NADH was available for reduction of the eIF5A-imine intermediate.

Hydrogen↗

PubMed2000

Postoperative neoadjuvant chemotherapy before radiotherapy as compared to immediate radiotherapy followed by maintenance chemotherapy in the treatment of medulloblastoma in childhood: results of the German prospective randomized trial HIT '91.

PURPOSE: The German Society of Pediatric Hematology and Oncology (GPOH) conducted a randomized, prospective, multicenter trial (HIT '91) in order to improve the survival of children with medulloblastoma by using postoperative neoadjuvant chemotherapy before radiation therapy as opposed to maintenance chemotherapy after immediate postoperative radiotherapy. METHODS AND MATERIALS: Between 1991 and 1997, 158 patients were enrolled and 137 patients randomized. Seventy-two patients were allocated to receive neoadjuvant chemotherapy before radiotherapy (arm I, investigational). Chemotherapy consisted of ifosfamide, etoposide, intravenous high-dose methotrexate, cisplatin, and cytarabine given in two cycles. In arm II (standard arm), 65 patients were assigned to receive immediate postoperative radiotherapy, with concomitant vincristine followed by 8 cycles of maintenance chemotherapy consisting of cisplatin, CCNU, and vincristine ("Philadelphia protocol"). All patients received radiotherapy to the craniospinal axis (35.2 Gy total dose, 1.6 Gy fractionated dose / 5 times per week followed by a boost to posterior fossa with 20 Gy, 2.0 Gy fractionated dose). RESULTS: During chemotherapy Grade III/IV infections were predominant in arm I (40%). Peripheral neuropathy and ototoxicity were prevailing in arm II (37% and 34%, respectively). Dose modification was necessary in particular in arm II (63%). During radiotherapy acute toxicity was mild in the majority of patients and equally distributed in both arms. Myelosuppression led to a mean prolongation of treatment time of 11.5 days in arm I and 7.5 days in arm II, and interruptions in 35% of patients in arm I. Quality control of radiotherapy revealed correct treatment in more than 88% for dose prescription, more than 88% for coverage of target volume, and 98% for field matching. At a median follow-up of 30 months (range 1.4-62 months), the Kaplan-Meier estimates for relapse-free survival at 3 years for all randomized patients were 0.70+/-0.08; for patients with residual disease: 0.72+/-0.06; without residual disease: 0.68+/-0.09; M0: 0.72+/-0.04; M1: 0.65+/-0.12; and M2/3: 0.30+/-0.15. For all randomized patients without M2/3 disease: 0.65+/-0.05 (arm I) and 0.78+/-0.06 (arm II) (p < 0.03); patients between 3 and 5.9 years: 0.60+/-0.13 and 0.64+/-0.14, respectively, but patients between 6 and 18 years: 0.62+/-0.09 and 0.84+/-0.08, respectively (p < 0.03). In a univariate analysis the only negative prognostic factors were M2/3 disease (p < 0.002) and an age of less than 8 years (p < 0.03). CONCLUSIONS: Maintenance chemotherapy would seem to be more effective in low-risk medulloblastoma, especially in patients older than 6 years of age. Neoadjuvant chemotherapy was accompanied by increased myelotoxicity of the subsequent radiotherapy, causing a higher rate of interruptions and an extended overall treatment time. Delayed and/or protracted radiotherapy may therefore have a negative impact on outcome. M2/3 disease was associated with a poor survival in both arms, suggesting the need for a more intensive treatment. Young age and M2/3 stage were negative prognostic factors in medulloblastoma, but residual or M1 disease was not, suggesting a new stratification system for risk subgroups. High quality of radiotherapy may be a major contributing factor for the overall outcome.

Adolescent↗

PubMed2000

Interstitial fluid pressure is increased in renal cell carcinoma xenografts.

The purpose of this study was to test the hypothesis that renal cell carcinoma (RCC) exhibits an increased intratumoral interstitial fluid pressure (IT-IFP). Therefore, resected tumors from human primary (n = 23) or metastatic RCC (n = 3) were xenografted in SCID mice. The IFP of single tumor nodules (n = 65) and normal mouse tissue (n = 195) was measured by means of the "wick-in-needle" technique. Data demonstrate that the mean IT-IFP at neoplasia was 35 times greater than in normal tissue, and decreased precipitously at the tumor boundary. IT-IFP values tended to increase with the grade of malignancy of the tumor cells and tumor size. The mean IT-IFP of xenografts derived from primary RCC was twice as high as that from metastatic RCC tissue. These findings indicate a biophysical barrier to drug delivery in RCC; this may, in concert with cellular-based drug resistance mechanisms, be an additional explanation for resistance of the tumor to certain blood-borne anticancer therapies.

Animals↗

PubMed2000

Genomic analysis of the vitellogenin locus in rainbow trout (Oncorhynchus mykiss) reveals a complex history of gene amplification and retroposon activity.

Vitellogenins (Vtg) are the major yolk proteins in most oviparous organisms. They are encoded by a small number of genes--between one and four depending on the species. Characterization of the Vtg region in the genome of the rainbow trout reveals unusual features, however, in that this locus contains twenty complete genes and ten pseudogenes per haploid genome. The Vtg genes differ from each other by insertion, deletion and rearrangement events, although, at the sequence level, they show a high degree of similarity. Fluorescent in situ hybridization (FISH), pulsed-field gel electrophoresis (PFGE) and Southern analysis indicate that all gene copies are contained in a single 1,500-kb region, and that most of the genes form tandem arrays separated by a conserved 4.5-kb intergenic region. The presence of large reiterated fragments indicates that this region has been subjected to several amplification events. The presence of a retroposon element (called 19) in Vtg intron 9 appears to be responsible for the silencing of at least nine of the ten pseudogenes. Two other incomplete retrotransposons (one LTR- and one LINE-type) and sequences derived from a HIV-like retrovirus are inserted into the conserved intergenic region, very close to the transcription start site. Their presence in all Vtg 5'-flanking regions suggests a possible role in gene amplification at this locus.

Animals↗

PubMed2000

Second malignancies in melanoma patients in Thuringia.

OBJECTIVE: The incidence of melanoma is increasing. Melanoma patients are at risk for the development of second neoplasias. Data for the new German Bundesländer are not available, but would be suitable to define frequency, site and type of secondary malignancies and conclusions for follow-up of melanoma patients. DESIGN: Retrospective study at the Melanoma Outpatient Clinic of the Department of Dermatology and Allergology at the University of Jena (Germany) for patients seen between June 1966 and June 1999. To investigate the impact of second malignancies on survival a case-comparison study of mortality was performed. The log-rank test and chi2-test were used to investigate statistical significance. There were 554 patients with malignant melanoma, 237 male and 317 female, with an age at time of diagnosis between 17.0 and 90.1 years (mean 53.7 years). The mean follow-up was 5.6 years. RESULTS: Sixty-one patients (11.0%) developed a second tumour. The total number of tumours was 83. Forty-five patients developed one, 16 developed > or = 2 second tumours. Basal cell carcinoma (BBC) was the most frequent neoplasia (17 patients, 22 tumours; mean age 64.9 years). A second melanoma was found in 15 patients, while two developed a third melanoma. The mean tumour thickness was 0.81 mm (in second or third melanomas) compared with 1.92 mm of primary melanomas. Seven female patients developed breast cancer (eight cancers; mean age 57.3 years). The other second tumours included skin cancer (eight), gastrointestinal tract tumours (four), genital cancers (19), brain tumours (two), lung cancer (two) and other tumours (six). The difference in survival of patients with second tumours was not statistically significant from age-, sex- and melanoma thickness-matched controls. CONCLUSIONS: Second malignancies were seen in 11.0% of melanoma patients. Most important are second skin tumours such as second melanomas and BCC, recommending follow-up by the dermatologist. In a group of patients with regular follow-up examinations, no negative impact of second tumours (BCC, melanoma, breast cancer) on overall survival could be detected.

Adolescent↗

PubMed2000

Anesthetic management of severe chronic cardiopulmonary failure during endovascular embolization of a PICA aneurysm: a case report.

The authors present a case in which a 64-year-old female patient suffering from severe cardiopulmonary dysfunction underwent endovascular embolization of an aneurysm of the posterior inferior cerebellar artery (PICA). The anesthetic management consisted of so-called dynamic akinetic sedation and controlled hemodynamics (DASCH) using intravenous propofol and dopamine infusions and invasive blood pressure monitoring. The details of the perioperative patient management are described. The patient made a successful recovery.

Anesthesia↗