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R Heinz

Publications and source records attributed to R Heinz.

At least 37 records · Page 2Linked to original sources
PubMed1996

Expression of G alpha 16, a G-protein alpha subunit specific for hematopoiesis in acute leukemia.

G-proteins are essential in signal transduction pathways. A G-protein alpha subunit termed G alpha 16 was found to be exclusively expressed in hematopoietic cell lines. In cells derived from patients, G alpha 16 expression has been detected in progenitor- and pre-B ALL cells and also in peripheral blood stem cells (PBSC). In this study, we analyzed G alpha 16 expression using a RT-PCR technique by testing elutriated blood cells from normal donors, PBSC from breast cancer patients and bone marrow or peripheral blood cells from acute leukemia patients. Both of two ALL patients and 15/16 AML patients expressed G alpha 16. In elutriation experiments, G alpha 16 expression was found in fractions containing the highest number of precursor cells but was absent in mature T and B cell fractions. In addition, CD34-enriched PBSC were positive for G alpha 16 expression. Further in vitro experiments using the cell line KG1 showed that G alpha 16 expression was not affected by the growth inhibiting hemoregulatory peptide pEEDCK which has a sequence homology present within G alpha 16. Taken together, these data demonstrate that G alpha 16 is expressed in various normal and malignant hematopietic progenitors but not in their differentiated counterparts. G alpha 16 could play a vital role in signal transduction pathways controlling proliferation in early normal and malignant hematopoiesis.

Acute Disease↗
PubMed1995

Fryns syndrome survivors and neurologic outcome.

Fryns syndrome is an autosomal recessive multiple congenital anomaly syndrome characterized by diaphragmatic hernia, unusual facies, and distal limb hypoplasia. It was first reported as a lethal condition. We report on a three-year-old survivor with Fryns syndrome, and provide a review on the outcome of other survivors. Patients who survive the neonatal period represent 14% of reported cases. Characteristics of survivors include less frequent diaphragmatic hernia and milder lung hypoplasia, absence of complex cardiac malformation, and neurologic impairment. Multiple central nervous system abnormalities have been reported in Fryns syndrome, including agenesis of the corpus callosum, Dandy-Walker abnormality, cerebellar heterotopias, cerebellar hypoplasia, enlarged ventricles, and hypoplasia of the olfactory bulbs. Our patient exhibited profound mental retardation. He had malformations of gyration and sulcation, particularly around the central sulcus, and hypoplastic optic tracts beyond the optic chiasm. Understanding of long-term outcome of survivors is important for counseling of families with Fryns syndrome. Careful brain examination is advised; however, a normal radiological brain examination does not preclude developmental delay. The spectrum of individual outcome and of associated anomalies indicates that individual evaluation, including imaging for structural brain malformation, is strongly advised.

Abnormalities, Multiple↗
PubMed1995

Multiple myeloma: high incidence of chromosomal aneuploidy as detected by interphase fluorescence in situ hybridization.

Because metaphase cytogenetic studies in multiple myeloma (MM) are hampered by a low proliferative activity of myeloma cells in vitro, interphase cytogenetics by means of fluorescence in situ hybridization (FISH) should improve the detection of chromosomal abnormalities in MM. We therefore investigated chromosomal aneuploidy in 36 patients with MM using interphase FISH and alpha-satellite DNA probes for chromosomes 1, 3, 7, 8, 11, 12, 16, 17, 18, and X. By FISH, myeloma cells from 32 patients (88.9%) were aneuploid for at least one of the chromosomes examined. In 24 patients (66%), aberrations of > or = 3 chromosomes were observed. Aneuploidy was predominantly characterized by a gain of chromosome numbers, with involvement of chromosomes 3, 7, and 11 occurring in > 50% of patients. Loss of a centromeric signal suggesting monosomy was most frequently observed for chromosomes 17 (22.2% of patients) and X (monosomic in 42.3% of female patients, but loss of chromosome X was never observed in males, P < 0.05). Dual-color FISH studies provided evidence for marked heterogeneity of aneuploid cells in 8 patients (22.8%). Occurrence of chromosomal aneuploidy was independent of stage and pretreatment status. Gain of chromosome 3 was significantly correlated with an IgA paraprotein (P < 0.05). In 12 patients, the direct comparison of metaphase cytogenetics and FISH showed that FISH detected aneuploidy of chromosomes in 9 patients that was missed by metaphase analysis. In conclusion, interphase FISH, by which chromosomal aneuploidy was detected in almost 90% of patients with MM, represents an approach for evaluating the clinical significance of specific chromosomal abnormalities in MM.

Adult↗
PubMed1995

Early detection of minimal residual disease by reverse transcriptase polymerase chain reaction predicts relapse in acute promyelocytic leukemia.

The PML/RAR alpha fusion RNA can be detected in acute promyelocytic leukemia (APL), cytogenetically characterized by the translocation t(15;17). Our study included ten newly diagnosed patients with APL who were investigated during the course of their diseases using reverse transcription polymerase chain reaction (RT-PCR). At diagnosis, aberrant fragments with a size heterogeneity due to alternative spliced products were detected in all patients, we observed breakpoints within bcr3 (short type) in two patients and bcr1 and 2 breakpoints (long type) in eight patients. Treatment consisted of all-trans retinoic acid (ATRA) in all patients; six patients received simultaneous cytostatic therapy during remission induction. At the time of complete hematological remission (CR), only two patients showed a negative RT-PCR result; eight of the ten patients were still PCR positive when nested primers were used. Subsequently, eight patients received consolidation chemotherapy and became PCR negative. Seven of eight patients are in continuous complete remission (median remission duration: 21 months, range: 11+ -26+ months). One patient of the chemotherapy group became PCR positive after 4 months in complete remission and relapsed after 6 months. The remaining two patients who were treated only with ATRA relapsed, received induction chemotherapy, and are in second and third complete remission, respectively. In conclusion. PCR negativity can be achieved only by chemotherapeutic consolidation; patients treated with ATRA alone remain PCR positive. Relapse is always preceded by a positive PCR result. Surprisingly, also patients without measurable PML/RAR alpha-mRNA in sequential analyses after cytostatic treatment became PCR positive and experienced relapse.

Adult↗
PubMed1995

Phorbol-12,13-dibutyrate improves the quality of cytogenetic preparation in lymphoid malignancies.

In cytogenetic preparation of lymphoid malignancies we investigated the quantitative and qualitative impact of phorbol-12,-13-dibutyrate (P) and of this tumor promoter in combination with the calcium ionophore A23187 (PA). Using parallel cultures of unstimulated and stimulated preparations, the effect was examined in 13 patients with malignant lymphomas and six patients with acute lymphoblastic leukemias (ALL). Focusing on high-quality analyzable metaphases, the best results were found in seven of 13 cases with lymphomas and five of six patients with ALL in the cultures supplemented with phorbol-12,13-dibutyrate. The yield of metaphases of good quality regarding length, spreading, and banding of chromosomes was regularly better in P-stimulated 24-hour culture (p < 0.05), followed by 48-hour cultures stimulated with P alone. Addition of the calcium-ionophore was of no further benefit. The yield of the unstimulated direct harvest was rather poor in nearly all patients investigated. Because no mutagenic effect of P was observed, the use of this mitogen may offer interesting perspectives in cytogenetic analysis of lymphoid malignancies and perhaps also in other tumors with low mitotic indexes.

Calcimycin↗
PubMed1995

B lymphocytes with latent EBV infection appearing in long-term bone marrow cultures (HLTBMCs) from haematological patients induce lysis of stromal microenvironment.

Human long-term bone marrow cultures (HLTBMCs) are a valuable in vitro model for studying the role of the haemopoietic microenvironment. Here we report the spontaneous appearance of EBV-positive B cells in 6/40 HLTBMCs from patients with various haematological diseases after 3-5 months of culture. After subcultivation of these cells, a novel type of cell line could be characterized, which displayed surface markers and morphological features typical for EBV transformed B-cell lines. As the deproteinized and ultrafiltrated culture supernatants of these cell lines were found to contain an agent with stroma toxic properties, they were termed SSB lines (stroma-toxic-agent-secreting B-cell lines). This agent also exhibited a colony-inhibitory activity on in vitro myelopoiesis and erythropoiesis. These properties are typical for the two polyamines spermine and spermidine which were detected at elevated levels in the culture supernatants of SSB lines. The hypothesis that latent presence of EBV in bone marrow may induce an increased synthesis of spermine and spermidine, which are known to be associated with malignant haematological diseases and bone marrow aplasia, is discussed.

B-Lymphocytes↗
PubMed1995

Ifosfamide, mitoxantrone and etoposide (VIM) as salvage therapy of low toxicity in non-Hodgkin's lymphoma.

Patients with non-Hodgkin's lymphoma (NHL) who fail to respond to first-line treatment or relapse after having shown complete or partial remission have a poor prognosis, especially in high-grade NHL. Several salvage regimens show considerable toxicity and a poor long-term outcome. In this retrospective study we analyzed data of 55 patients (34 men and 21 women) with a median age of 66 years (range: 18-89). The combination chemotherapy (VIM) consisted of VP-16 (etoposide) 65 mg/m2, ifosfamide 650 mg/m2 and mitoxantrone 3 mg/m2 and was administered on 3 consecutive days along with mesna as uroprotection. Patients were treated for refractory disease or relapse and did not qualify for high-dose chemotherapy and ABMT. Stages according to the An Arbor classification were: stage I/16, II/4, III/8 and IV/37 patients. Thirty-three patients suffered from high-grade and 22 from low-grade NHL. Toxicity (WHO recommendations) was very mild. High-grade NHL showed a better response rate (18/33, 46%) than low-grade NHL (7/22, 36%). Overall response was 41% (12 CR and 11 PR) with a median duration of 36 months (range: 6-57 months). The combination therapy investigated exhibits mild toxicity even in extensively pretreated or elderly patients. The overall response rate of 41% might be improved by increased dosage and growth factor support.

Adolescent↗
PubMed1995

[Experiences with anti-Rhesus-D therapy in pretreated patients with idiopathic thrombocytopenia].

OBJECTIVE: We tested the effect of anti Rhesus D [anti Rh(D)]-specific IgG in heavily pretreated patients with idiopathic thrombocytopenic purpura (ITP). DESIGN: Retrospective single case studies. SETTING: Clinical department of hematology. PATIENTS: 6 consecutive patients with heavily pretreated therapy-refractory ITP. INTERVENTIONS: 5 patients received one cycle of Anti Rh(D) in doses between 1,200 and 6,000 micrograms in 1 patient 2 consecutive cycles were applied. Treatment effect, durability, and side effects were monitored. RESULTS: Patients after splenectomy and/or immunosuppressive therapy did not respond. Response was short-lived in 2 other patients, one long-term remission could be achieved. Responders showed slight decreases in hemoglobin indicating mild hemolysis. Other major side effects were not observed and the therapy was well tolerated. CONCLUSIONS: Our results suggest that therapy with Anti Rh(D) is safe and comparably inexpensive. No clear dose/effect correlation was found in our investigation. Only patients with platelet sequestration into the spleen might respond to Anti Rh(D) therapy.

Adult↗
PubMed1995

Analysis of peripheral blood progenitor cells demonstrates limitations of minimal residual disease diagnosis in a case of acute promyelocytic leukemia.

Detection of minimal residual disease (MRD) by analysis of the PML-RAR alpha fusion transcript using the RT-PCR method is routinely carried out on peripheral blood and bone marrow of patients with APL (AML, FAB:M3). Therapy aims to achieve repeated negative results in these patients thus confirming clinical complete remission. We report a case of APL in second complete remission in which no leukemic cells had been detected in BM and PB for 20 months, and in which PBPC-pheresis was carried out for future transplantation. In two of five pheresis PML-RAR alpha fusion transcripts were detected. This shows that the residual leukemic population may only reach detection level after enrichment by PBPC-pheresis.

Adult↗
PubMed1995

Detection of cerebrospinal fluid metastasis: CT myelography or MR?

PURPOSE: To determine the sensitivity of contrast MR versus myelography followed by CT in the detection of cerebrospinal fluid metastases in children with primary central nervous system tumors. METHODS: Thirty-three patients who had primary central nervous system malignancies had spinal MR with gadolinium within 2 weeks of a myelogram followed by CT. MR technique included T1-weighted image sequences of the entire spine with and without gadolinium. CT scans were routinely performed at T-12 to L-2, L-4 to S-1, and foramen magnum to C-2. All studies were reviewed blindly; the number, character, and location of all metastases was recorded and the results of the two studies compared. Cerebrospinal fluid cytologic findings were recorded for each patient, and compared with the results of the imaging studies. RESULTS: Seven of the 33 patients had metastases detected; metastases were seen on both MR and myelography followed by CT. However, MR showed 24 lesions and myelography followed by CT showed only 15. When a lesion was seen on both MR and myelography followed by CT, the MR was usually more convincing. Superficial lesions seen on MR sometimes would be missed on myelography followed by CT. Both MR and myelography followed by CT were quite sensitive in the detection of small lesions (2 to 3 mm) when present on spinal nerve roots. Whereas MR showed multiple lesions not seen on myelography followed by CT, CT failed to show any metastases not seen on MR. Imaging studies showed metastases in 3 patients who had normal cytologic findings. CONCLUSIONS: MR shows significantly more cerebrospinal fluid metastases than myelography followed by CT.

Adolescent↗
PubMed1994

Differential utilization of alternate initiation sites in a plant defense gene responding to environmental stimuli.

The upstream regulatory region of an efficiently expressed phenylalanine ammonia-lyase (PAL5) gene from tomato (Lycopersicon esculentum) was characterized by DNA sequencing and S1-nuclease-protection studies. Two transcription initiation sites giving rise to a long and a short transcript were identified, each corresponding to a different putative TATA sequence element with multiple conserved upstream regulatory motifs. When tomato plants were challenged with three different environmental stimuli, wounding, light and Verticillium infection, this gene was observed to utilize the alternate initiation sites differentially, in a tissue-dependent and stimulus-dependent manner. In general, basal levels of the shorter transcript were very low but preferentially and strongly stimulated by the environmental factors. In contrast, the longer transcript was less affected, essentially representing a constitutive expression of this gene. The results suggest that the multiple regulatory sites in the PAL5 gene promoter provide for both an essential constitutive expression of phenylalanine ammonia-lyase as well as an appropriate response to different environmental stresses.

Amino Acid Sequence↗
PubMed1994

Peripheral T-cell non-Hodgkin's lymphomas of low malignancy: prospective study of 25 patients with pleomorphic small cell lymphoma, lymphoepitheloid cell (Lennert's) lymphoma and T-zone lymphoma. The Kiel Lymphoma Study Group.

Peripheral T-cell lymphomas comprise a heterogenous group of low- and high-grade malignancies differing in their histopathological appearance and also in clinical and prognostic aspects. We prospectively studied 25 patients with low-grade peripheral T-cell lymphomas: pleomorphic, small cell lymphoma (PSC) (n = 9), lymphoepitheloid (Lennert's) lymphoma (LEL) (n = 12) and T-zone lymphoma (TZL) (n = 4). The median patient age was 55 years (range 19-75 years); the male to female ratio was 1.5. 13 patients (52%) had limited stages (I+II), 12 patients (48%) had advanced disease (stage III+IV). 21 patients received the COPBLAM/IMVP-16 regimen. Two patients received more intensive treatments; two received less intensive therapy. Complete remissions were achieved in 16/25 patients (64%). The median observation time of surviving patients was 30 months (range 5-72 months). The actuarial overall survival and event-free survival at 2 years of 21 patients receiving COPBLAM/IMVP-16 were 69% and 35%, respectively. Intensive chemotherapy led to complete remissions in about 60% of the patients and to long-term disease-free survival for one-third. The observed clinical courses illustrate the aggressive nature of PSC, LEL and TZL.

Adult↗