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J Wolf

Publications and source records attributed to J Wolf.

At least 109 records · Page 6Linked to original sources
PubMed1999

Morphologically normal, CD30-negative B-lymphocytes with chromosome aberrations in classical Hodgkin's disease: the progenitor cell of the malignant clone?

A recent study observed that numerical chromosome abnormalities in Hodgkin's disease (HD) are detected not only in morphologically abnormal Hodgkin/Reed-Sternberg cells, but also in a fraction of morphologically normal cells. However, the phenotypic constitution of these genetically abnormal, morphologically normal cells and their relationship to the malignant Hodgkin/Reed-Sternberg cells could not be established in the earlier cases studied, because of the low frequency of these cells. The present study investigated two cases of classical Hodgkin's disease containing a relatively large population of such apparently normal cells with aberrant chromosome copy numbers. The phenotype and their position within the developmental route of the malignant compartment were examined by a combined in situ hybridization and immunocytochemistry approach. Numerical abnormalities for chromosome 1 in one case and for chromosomes X, Y, and 1 in the other case were observed not only in CD30-positive Hodgkin/Reed-Sternberg cells, but also in CD30-negative, morphologically normal cells. It was shown that these genetically aberrant cells expressed the B-cell antigen CD19, thus confirming their B-cell nature. These studies indicate a relationship between the genome aberrations in these genetically abnormal, morphologically normal B-cells and the Hodgkin/Reed-Sternberg cells, suggesting that they are progenitor cells of the malignant cell fraction.

Adult↗
PubMed1999

Combination benefit of PEGylated soluble tumor necrosis factor receptor type I (PEG sTNF-RI) and dexamethasone or indomethacin in adjuvant arthritic rats.

OBJECTIVE: To determine the potential combination benefit receptor of treatment with PEGylated soluble tumor necrosis factor type I (PEG sTNF-RI) and dexamethasone (dex) or indomethacin (indo) in adjuvant arthritic rats. SUBJECTS: 160 male Lewis Rats. TREATMENT: PEG sTNF-RI, dex, indo. METHODS: Rats with adjuvant arthritis were given daily oral dex (0.025 or 0.006 mg/kg) or indo (0.5 or 0.25 mg/kg) day 9-14, alone or in combination with PEG sTNF-RI (sc on days 9, 11, and 13 of arthritis). Efficacy was monitored by volume measurement of ankle joints, final paw weights and histologic evaluation with particular emphasis on bone lesions. RESULTS: Treatment with 1 mg/kg PEG sTNF-RI alone resulted in 27% inhibition of final paw weights, dex alone (0.025 mg/kg) gave 25% inhibition and the combination resulted in 58% inhibition. Histologic evaluation of ankle joints demonstrated 48% inhibition of bone resorption with PEG sTNF-RI alone, 55% inhibition with dex alone and the combination treatment inhibited bone resorption by 100%. Inactive doses of PEG sTNF-RI (0.3 mg/kg) and dex (0.006 mg/kg) when combined resulted in 39% inhibition of paw swelling (AUC) and 39% inhibition of bone resorption. Combination treatment with indomethacin resulted in slight additive effects on inflammation parameters but no additive effects on bone resorption. CONCLUSION: Combination therapy with PEG sTNF-RI and dexamethasone results in additive or synergistic effects depending on the dose. Combination therapy with indomethacin resulted in slight additive effects on paw swelling parameters, but no additive benefit on bone resorption. Data from these studies support the clinical investigation of the use of combination therapy of PEG sTNF-RI and dex or other corticosteroids in rheumatoid arthritis patients.

Animals↗
PubMed1999

S-cone ERGs elicited by a simple technique in normals and in tritanopes.

PURPOSE: To measure changes in the relative spectral sensitivities of the dark adapted and light adapted ERG and thus to establish the possible contribution of rods to the 'blue cone' ERG elicited by flashes of blue light. BACKGROUND: Short wavelength stimuli in the light-adapted eye evoke small rounded b-waves which have been considered to be S-cone responses. We have recorded such responses from tritanopes, which called the assumptions into question. METHODS: Small ERGs were recorded to blue and green flashes. The stimulus was a Ganzfeld which employed light emitting diodes. ERGs were obtained in both the dark-adapted eye and after light adaptation to intense orange light (peak wavelength 610 nm). The change in sensitivity with light adaptation and the relative spectral sensitivity was determined from the voltage/log light intensity functions, using a 10 microV criterion. RESULTS: (1) peak times and changes in sensitivity did not help distinguish light-adapted rod from possible S-cone responses; (2) analysis of the change in the ratio of blue:green sensitivity from darkness to 4.4 log Td. 610 nm background suggests that in seven normal subjects, 90% or more of the ERG evoked by 440 nm flashes is generated by S-cones; (3) three tritanopes have insignificantly reduced S-cone responses. CONCLUSIONS: (1) clinical techniques used to isolate S-cone ERGs are appropriate; (2) there are at least two types of tritanope and in those we investigated, functional S-cones are probably displaced into the retinal periphery.

Adaptation, Ocular↗
PubMed1999

Successful peripheral blood stem cell mobilization with etoposide (VP-16) in patients with relapsed or resistant lymphoma who failed cyclophosphamide mobilization.

High-dose chemotherapy (HDCT) followed by autologous blood stem cell transplantation is considered the treatment of choice for patients with relapsed or resistant aggressive non-Hodgkin's lymphoma (NHL) or Hodgkin's disease (HD). However, several authors report failure of standard mobilization regimens in 29% to 56% of these patients making the completion of HDCT impossible and as a result, negatively influencing long-term outcome. Thus, effective new regimens for patients failing initial mobilization are needed. Here we report the results of using etoposide as a mobilizing agent in 16 patients with primary resistant or relapsed malignant lymphoma who had failed prior mobilization of peripheral blood stem cells (PBSC) with cyclophosphamide (4 g/m2) followed by G-CSF. The use of etoposide 500 mg/m2 (days 1-4) + G-CSF resulted in the successful collection of adequate numbers of PBSC with a median harvest of 3.6 x 10(6)/kg (range 2.2-12.6) CD34+ cells in all 16 patients. In 7/16 (44%) patients, the target yield of at least 2.0 x 10(6) CD34+ cells was harvested by a single apheresis and the maximum number of separations for all patients was two. No excessive toxicities appeared, allowing all patients to proceed to myeloablative chemotherapy. In addition, median peak values of circulating CD34+ cells were significantly higher after etoposide as compared to cyclophosphamide (49.2/microl vs 4.7/microl; P = 0.0004). These results indicate that etoposide + G-CSF is a highly effective mobilization regimen in patients who have failed cyclophosphamide mobilization.

Adult↗
PubMed1999

Detection of a Hodgkin/Reed-Sternberg cell specific immunoglobulin gene rearrangement in the serum DNA of a patient with Hodgkin's disease.

We analysed multiple serum samples from a patient with mixed cellularity Hodgkin's disease for the Hodgkin/Reed-Sternberg cell clone-specific rearranged Ig gene sequence. The clone-specific sequence could be detected in DNA extracted from a serum sample obtained during clinical relapse but not in serum samples obtained during or after treatment following relapse.

Adult↗
PubMed1999

Factor structure of the Neurobehavioral Cognitive Status Exam (COGNISTAT) in healthy, and psychiatrically and neurologically impaired, elderly adults.

This study reports the results of factor analyses of COGNISTAT (NCSE) in a sample of elderly persons comprised of "healthy" participants with no psychiatric or neurological impairments (n = 153), individuals with psychiatric impairments (n = 70), and those with neurological impairments (n = 80). Our findings support a unitary factor structure for COGNISTAT, though a separate factor of unclear clinical or theoretical significance was suggested.

Adult↗
PubMed1999

Chronic pain management in a health maintenance organization.

OBJECTIVE: The purpose of this study is to investigate the management of chronic pain in a large health maintenance organization using cognitive-behavioral techniques and a blinded control group. DESIGN: Subjects were randomized into two groups. All participants completed a self-administered baseline questionnaire and were mailed a self-administered 6-month follow-up questionnaire. SETTING: This study examines chronic pain management in a large, established health maintenance organization. PATIENTS: Patients were members of a health maintenance organization, had pain for at least 6 months, and had failed all known treatment regimens. INTERVENTIONS: The treatment group participated in a 16-hour, 8-week class teaching cognitive-behavioral techniques, the relaxation response, meditation, and stress management. The minimal treatment group received a home-study manual. OUTCOME MEASURES: Behavioral outcomes, function, and pain severity and also patient satisfaction were measured. RESULTS: Both the treatment and minimal treatment groups exhibited improvement in pain severity, negative mood, pain affect, and pain interference with the patient's life. CONCLUSION: Gains were achieved in pain severity, negative mood, pain affect, self-control, and pain interference with the patient's life. Other behavioral variables and activity did not improve. Except in self-control, pain affect, and distracting responses from their significant others, the blinded minimal treatment group demonstrated similar findings. Patient satisfaction with treatment strongly favored the treatment group with over 78% of the treatment participants satisfied with the care provided.

Adult↗
PubMed1999

Cecal volvulus in pregnancy.

Colonic volvulus is an important entity to consider in any pregnant patient with abdominal pain. X-ray and colonoscopy can be useful to obtain the earliest diagnosis, leading to surgical intervention if necessary. Limited use of x-rays with shielding of the fetus is of minimal risk and useful for early diagnosis of volvulus. Colonoscopy may confirm or exclude the diagnosis of colonic volvulus, detect mucosal ischemia, and avoid the requirement for emergency surgery by reducing the volvulus in cases in which ischemia is not present. If surgery is necessary for a cecal volvulus, cecostomy is a viable option because of a low rate of morbidity and subsequent volvulus recurrence.

Adult↗
PubMed1999

Expression of epstein-barr virus nuclear antigen 1 is associated with enhanced expression of CD25 in the Hodgkin cell line L428.

Epstein-Barr virus is associated with several human malignancies including Burkitt's lymphoma, nasopharyngeal carcinoma, and Hodgkin's disease (HD). To examine the effect of Epstein-Barr virus nuclear antigen 1 (EBNA-1) in the pathogenesis of HD, we transfected the gene into the HD cell line L428. EBNA-1 expression was associated with significantly enhanced CD25 expression (interleukin 2 [IL-2]-receptor alpha chain) in transient and stably transfected L428 cells but did not affect the expression of IL-2 receptor beta and gamma chains. There was no up-regulation of the B-cell activation molecules CD23, CD30, CD39, CD40, CD44, CD71, and CD54 (intercellular adhesion molecule 1) or enhanced production of IL-6, IL-10, lymphotoxin alpha, and the soluble form of CD25. Stable EBNA-1-expressing L428 cells were nontumorigenic in SCID mice but showed enhanced lymphoma development in nonobese diabetic-SCID mice compared to mock-transfected cells.

Animals↗
PubMed1999

Dexa-BEAM is not effective in patients with relapsed or resistant aggressive high-grade non-Hodgkin's lymphoma.

The aim of the present study was to evaluate the feasibility and response of the Dexa-BEAM regimen as a salvage therapy followed by high-dose chemotherapy (HDCT) with peripheral blood stem cell transplantation (PBCST) in responding patients with high-grade relapsed or resistant aggressive non-Hodgkin's lymphoma (NHL). Sixteen pretreated patients (mean age 44, range 26-59) with relapsed (8) or resistant (8) NHL were treated with 1-4 cycles of Dexa-BEAM (dexamethasone, BCNU, etoposide, cytarabine, melphalan) in order to attain maximal response. Patients achieving complete response (CR) or partial response (PR) received HDCT with PBSCT. The conditioning regimen used was BEAM. Three patients achieved CR and one patient PR, resulting in an overall response rate of 25%. Three of four responding patients underwent high-dose chemotherapy and were successfully transplanted with autologous blood stem cells. Progressive disease developed in one patient after transplantation. Myelosuppression (WHO grade III- grade IV), the major side effect, was observed in all courses of Dexa-BEAM. Myelosuppression-related infection WHO grade IV occurred in four patients. The protocol was not well tolerated in this heavily pretreated group of patients with four severe myelosuppression-related infections WHO grade IV and one treatment-related death. The overall response rate in this study is not comparable to other salvage regimens published and led to the discontinuation of the trial. In conclusion Dexa-BEAM was only effective in a minority of patients with refractory or relapsed aggressive NHL and was not useful as a cytoreductive regimen prior to HDCT.

Adult↗
PubMed1999

Treatment of advanced Hodgkin's lymphoma: standard and experimental approaches.

The introduction of polychemotherapy and improved radiation techniques has transformed Hodgkin's lymphoma from an incurable disease to a malignancy with one of the highest cure rates. Milestones were the development of the MOPP (mechlorethamine, vincristine, procarbazine, and prednisone) and ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine) regimens. Radiotherapy is commonly used, although its precise role has not been defined for patients with advanced-stage disease. More recently, dose-intensified schedules such as Stanford V (doxorubicin, vinblastine, mechlorethamine, vincristine, bleomycin, etoposide, and prednisone) were shown to be effective in this group of patients. In particular, the BEACOPP regimen (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone), in both standard and escalated doses, has produced impressive results in a randomized three-arm study when compared with COPP (cyclophosphamide, vincristine, procarbazine, and prednisone)/ABVD. The significantly higher rates of complete remission (CR) and freedom from treatment failure (FFTF) suggest that the new BEACOPP regimen improves efficacy, but definitive conclusions require further years of follow-up evaluation. Interestingly, BEACOPP abrogates the impact of the newly described seven-factor prognostic scoring system that was reported for patients treated with MOPP/ABVD or similar regimens. The prognostic index includes factors such as serum albumin, hemoglobin, male sex, stage IV disease, age more than 45 years, white blood cell count, and lymphocyte count. Whereas patients with Hodgkin's lymphoma have a good prognosis on first diagnosis, those with relapsed or refractory disease face a poor outcome.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1998

Visual processing levels revealed by response latencies to changes in different visual attributes.

Visual latencies, and their variation with stimulus attributes, can provide information about the level in the visual system at which different attributes of the image are analysed, and decisions about them made. A change in the colour, structure or movement of a visual stimulus brings about a highly reproducible transient constriction of the pupil that probably depends on visual cortical mechanisms. We measured this transient response to changes in several attributes of visual stimuli, and also measured manual reaction times to the same stimulus changes. Through analysis of latencies, we hoped to establish whether changes in different stimulus attributes were processed by mechanisms at the same or different levels in the visual pathway. Pupil responses to a change in spatial structure or colour are almost identical, but both are ca. 40 ms slower than those to a change in light flux, which are thought to depend largely on subcortical pathways. Manual reaction times to a change in spatial structure or colour, or to the onset of coherent movement, differ reliably, and all are longer than the reaction time to a change in light flux. On average, observers take 184 ms to detect a change in light flux, 6 ms more to detect the onset of a grating, 30 ms more to detect a change in colour, and 37 ms more to detect the onset of coherent motion. The pattern of latency variation for pupil responses and reaction times suggests that the mechanisms that trigger the responses lie at different levels in cortex. Given our present knowledge of visual cortical organization, the long reaction time to the change in motion is surprising. The range of reaction times across different stimuli is consistent with decisions about the onset of a grating being made in V1 and decisions about the change in colour or change in motion being made in V4.

Adult↗
PubMed1998

Stable nontumorigenic phenotype of somatic cell hybrids between malignant Burkitt's lymphoma cells and autologous EBV-immortalized B cells despite induction of chromosomal breakage and loss.

Fusion of the highly tumorigenic Burkitt's lymphoma (BL) cell line BL60-P7 with the nontumorigenic autologous EBV-immortalized lymphoblastoid cell line (LCL) IARC 277 results in suppression of the tumorigenic phenotype of the parental cell line BL60-P7 after s.c. inoculation into T cell-deficient nude mice. We analyzed whether, after long-term cultivation of these lymphoma hybrid cells, expression of tumorigenicity could be observed and correlated to the loss of particular chromosomes or chromosomal fragments, akin to numerous nonlymphoid hybrid cell models described previously. Two years after fusion, in vitro proliferation of some BL x LCL hybrid cells accelerated, and they partially lost LCL-typical aggregation. However, no major changes in the expression pattern of B cell-associated surface antigens and the EBV latent membrane protein LMP 1 were observed. Cytogenetic evaluation of these cells revealed spontaneous loss of chromosomes. Karyotyping of long-term cultivated hybrid cells demonstrated the occurrence of disomy for each chromosome in at least one metaphase analyzed. Therefore, if suppression of tumorigenicity in these hybrid cells would have been the result of the presence of a single LCL-derived chromosome, there should have been a high probability of its loss, leading to tumorigenic segregants. Surprisingly, the tumorigenic phenotype remained suppressed in nude mice. To induce chromosomal breakage and maldistribution, in addition to spontaneous chromosomal loss, the hybrid cell lines were irradiated at various doses. Again, none of the hybrid cell clones treated in this manner became tumorigenic in nude mice. Immunohistological analysis of the regressing hybrid cell tumors revealed that the hybrid cells had retained their LCL-like differentiation phenotype in vivo. In addition, infiltration with mononuclear cells of murine origin was observed in these regressing hybrid grafts. We conclude that suppression of the tumorigenic Burkitt's lymphoma phenotype in these hybrid cells cannot be attributed to a function encoded by a distinct chromosome or chromosomal fragment. Rather, the unexpected stable nontumorigenic phenotype reflects a LCL-specific activated B-cell phenotype of these hybrids, most probably induced by the expression of numerous copies of episomal latent EBV proteins.

Animals↗
PubMed1998

[Pathogenesis and therapy of Hodgkin lymphoma].

Although the pathogenesis of Hodgkin's disease is not clear, molecular analyses reveal characteristic features. EBV infection can be demonstrated in more than 50% of cases at the DNA or protein level. Recently, immunoglobulin gene rearrangements were found in single Hodgkin and Reed-Sternberg cells. Sequence analyses revealed that the rearranged Ig genes have frequently somatic mutations, which indicate that the cells are derived from the germinal center. These rearrangements may be used as defined markers to detect residual disease after chemotherapy. Modern polychemotherapy regimen and radiotherapy are very effective, and 60-90% of patients, depending on stage of the disease and risk factors, can be cured. Salvage therapy for relapsed patients including high-dose chemotherapy with autologous stem cell support frequently results in remission although duration is frequently short. New immunotherapy strategies with immunotoxins or bispecific antibodies are currently analysed in clinical studies.

Combined Modality Therapy↗
PubMed1998

An N-end rule destabilization mutant reveals pre-Golgi requirements for Sec7p in yeast membrane traffic.

Sec7 protein (Sec7p) is required for membrane traffic in the yeast secretory pathway. Because Sec7p regulates more than one stage in the pathway, it has been difficult to assign the most proximal requirement for Sec7p action. We have engineered a novel mutant whose Sec7p levels are regulated by growth conditions and by selective protein destabilization according to the N-end rule. Sec7p depletion causes cell growth arrest and accumulation of transport proteins with post-translational modifications indicative of Sec7p dependence for ER-to-Golgi traffic, in addition to the already characterized Golgi requirements. Immuno-EM of sec7 revealed exaggeration of ER and Golgi membranes with protein accumulation in these exaggerated structures, suggesting that these regions may represent staging areas for cargo sorting and vesicle assembly.

Biological Transport, Active↗
PubMed1998

Age-dependent neurotransmitter plasticity of ciliary ganglion neurons.

We have examined neurotransmitter plasticity in postmitotic cholinergic neurons isolated from 6.5- to 11-day-old embryonic quail ciliary ganglia. Purified neurons were labeled with DiI, transplanted into the trunk of young chick embryos, and assayed for catecholamine content and [3H]thymidine uptake 4 to 5 days later. For ciliary neurons derived from 6.5- to 8-day-old embryos, as many as 25% (average of 9% overall) expressed catecholamines in the host sympathetic ganglia, migratory stream, aortic plexuses, and adrenal medulla. In contrast, neurons from >8-day-old ganglia did not acquire or produce detectable catecholamines, indicating a limited time period over which phenotypic conversion can occur in vivo. As a control, ciliary neurons were also injected into the head mesenchyme of young embryos; no catecholamine expression was observed. Interestingly, after transplantation some DiI-labeled postmitotic ciliary neurons took up [3H]thymidine with or without phenotypic change. These results suggest that phenotypic plasticity in ciliary neurons is age-dependent, is location-dependent, and may involve resumption of DNA replication, a characteristic feature of some differentiating adrenergic sympathetic neurons. Apoptosis of a few proliferating transplanted cells may be induced independently or in association with transmitter change.

Adrenal Medulla↗