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Biomedical subjects

G Heil

Publications and source records attributed to G Heil.

At least 91 records · Page 5Linked to original sources
PubMed1988

Establishment of two Epstein-Barr virus negative Burkitt cell lines from a patient with AIDS and B-cell lymphoma.

To analyze the pathogenesis of B-cell lymphomas in patients with acquired immunodeficiency syndrome (AIDS), we studied two cell lines, Es I and Es III, established from one such lymphoma for the presence of sequences of the Epstein-Barr virus (EBV) and the human immunodeficiency virus [HIV; lymphadenopathy-associated virus (LAV/HTLV-III)] as well as for the presence of cytogenetic abnormalities and monoclonal rearrangements of immunoglobulin and T-cell receptor genes. Both cell lines expressed the same IgM, kappa phenotype as the original lymphoma. The karyotype of Es I was 46, XY, t(8;14), 2 p+, inv (6p), 17p-, and the cells of Es III had an additional i(7q). Immunoglobulin gene studies demonstrated the identical monoclonal rearrangements in both cell lines. Neither EBV nor HIV sequences were detectable in the malignant B cells at the genomic level, leading to the conclusion that mechanisms other than transformation by EBV or HIV may have contributed to the B-cell lymphoma in this patient and possibly also to the generally increased frequency in patients with AIDS.

Acquired Immunodeficiency Syndrome↗
PubMed1988

Ambiguous phenotypes and genotypes in 16 children with acute leukemia as characterized by multiparameter analysis.

Ambiguous phenotypes and genotypes were observed in 16 children with acute leukemia. Surface marker, cytogenetic, molecular genetic, and DNA flow cytometric analyses as well as standard morphologic and cytochemical studies were used to divide the patients into three groups. The first group comprised five children with acute leukemia whose blast cells were morphologically lymphoid, while immunophenotyping disclosed simultaneous expression of early pre-B cell and myeloid features. Molecular genetic studies showed evidence of heavy-chain immunoglobulin (Ig) gene rearrangements in all patients. Cytogenetic data, available in three of these children, revealed t(4;11). In five of the 16 patients, morphologic and surface marker analyses indicated the coexistence of two separate cell populations, one with myeloid and the other with early pre-B cell features. Further evidence of B cell commitment in these patients was provided by demonstration of Ig heavy-chain gene rearrangements in all five patients. Surprisingly, one of the five patients showed oligoclonal Ig heavy-chain as well as monoclonal gene rearrangement for the beta chain of the T cell receptor (beta-TCR). The last group consisted of four cases with otherwise typical acute lymphoblastic leukemia (ALL), early pre-B cell phenotype, and coexpression of myeloid or T cell-associated antigens, and two children with unequivocal acute myeloid leukemia (AML) and coexpression of T cell antigens. Gene rearrangement of Ig heavy-chain could be demonstrated in five of six patients, additional Ig light-chain gene rearrangement in two children with ALL, and bigenotypic features (Ig heavy-chain and beta-TCR gene rearrangement) in one patient. In none of the 16 patients did flow cytometry disclose clonal abnormalities of leukemic cell DNA content. Based on these findings, we suggest that malignant transformation in the first and second group of patients took place at a stage ontogenetically close to the pluripotent stem cell, whereas ambiguous phenotypes in the third group resulted from aberrant gene expression or insufficient reagent specificity.

Acute Disease↗
PubMed1988

Prognostic factors in a multicenter study for treatment of acute lymphoblastic leukemia in adults.

In a prospective multicenter study, 368 acute lymphoblastic leukemia (ALL) patients aged 15 to 65 years were treated with an intensified induction and reinduction regimen; 272 (73.9%) achieved complete remission (CR). The median remission duration (MRD) is 24.3 months, and the probability of being in continuous CR (CCR) at greater than 5 years is .37. The median survival for all 368 patients is 27.5 months, and the probability of being alive at 5 years is .39. For the 272 patients in remission the median survival is 58.4 months, and the probability of being alive at 5 years is .49. A lower CR rate was seen for patients with bleeding at diagnosis or with splenomegaly/hepatosplenomegaly. The prognostic factors unfavorable for remission duration were time to CR greater than 4 weeks v less than 4 weeks (P = .0002), age greater than 35 years v less than 35 years (P = .0008), leukocyte count greater than 30,000/microL v less than 30,000/microL (P = .0112), and null ALL v common ALL (c-ALL)/T cell ALL (T-ALL) (P = .05). The remission duration correlated strongly (P = .0001) with the number of these independent prognostic factors. In patients with none of these adverse factors the MRD has not yet been reached, with one adverse factor the MRD is 21.9 months, and with two or three adverse factors the MRD is only 9.6 months. For the immunologic subtype T-ALL, the probability of being in CCR at greater than 5 years is .55; for c-ALL, .34; and for null ALL, .24. According to these results, patients were stratified into a low-risk group with a CCR rate of .62 and a high-risk group with a CCR rate of .28, with the latter now allocated to either further chemotherapy or bone marrow transplantation in first remission.

Adolescent↗
PubMed1987

In vitro differentiation of a null-acute leukemia: T-lymphoid surface antigen expression associated with rearrangement in T-cell receptor beta chain variable genes.

We describe a human acute unclassified leukemia with a unique t(4;17) translocation that coexpresses T-lymphoid and myeloid surface antigens after in vitro culture in the presence of the tumor promoter, TPA. Under these conditions, the joining regions of the immunoglobulin heavy chain and T-cell receptor gamma and beta chain complexes remained in germ line configuration. A T-cell receptor beta chain variable gene probe, however, revealed the presence of rearrangements in the V beta M3-2 gene region after bilineage differentiation. These results may be pertinent to the interrelationship of T-cell receptor gene rearrangements and the control of T-cell antigen surface expression.

Acute Disease↗
PubMed1987

Human acute unclassified leukemia with a unique t(4;17) chromosomal translocation expresses T lymphoid and myeloid surface antigens after in vitro culture.

Bilineage differentiation along both the T lymphoid and the myeloid lineage while in in vivo diffusion chamber (DC) and in vitro suspension culture was observed in a case of acute unclassified leukemia (null-AL) and t(4;17). Prior to culture, the blast cells were TdT and la positive but did not express any lineage-specific antigenic markers. Furthermore, the immunoglobulin heavy chain and T cell receptor beta-chain genes were in germline configuration. Cytogenetically, all metaphases had the unique translocation t(4;17) (q25;q23) prior to and after culture, supporting the leukemic origin of the cells. During both DC culture and suspension culture with and without tetradecanoyl-phorbol-acetate (TPA), a substantial increase in the absolute and relative number of cells expressing both myeloid and T lymphoid antigenic markers occurred. Double-fluorescence analysis demonstrated the expression of antigenic markers of both lineages on the same population of cells, and electron microscopy revealed the induction of myeloperoxidase after both DC and suspension culture. Immunoglobulin heavy chain and T cell receptor beta-chain genes remained in germline configuration after treatment with TPA, when analyzed with JH and CT beta probes, respectively. These findings indicate that this case represents a null-AL with dual-lineage capabilities, which has probably arisen from the malignant transformation of a bipotential stem cell of lymphoid and myeloid progeny.

Antigens, Neoplasm↗
PubMed1986

Deficient IFN alpha production in hairy cell leukemia.

Since the application of low doses of IFN-alpha is necessary to maintain remissions in Hairy Cell Leukemia (HCL) it is of interest whether peripheral blood mononuclear cells (MNC) of HCL patients can be induced in vitro to produce IFN-alpha. 9 patients suffering from advanced HCL were included in the study. The diagnoses were confirmed by characteristic findings in peripheral blood and bone marrow biopsies. For IFN treatment we initially used natural IFN-alpha (Bioferon) and switched later to recombinant IFN-alpha2 (Boehringer). MNC of 5 patients before IFN therapy and of 6 patients during IFN therapy (2-47 weeks) were induced by phytohemagglutinin (PHA), Corynebacterium parvum (C.p.), and sendai virus (SV). PHA is known to induce IFN-gamma. Both, C.p. and SV induced IFN-alpha but no IFN-gamma in MNC of healthy controls and of IFN treated breast cancer patients. In HCL patients normal antiviral activities could be induced by PHA. Zero or only low antiviral activities could be induced in MNC from 9 patients tested on 22 occasions. It is concluded that MNC from patients with advanced HCL can be induced to produce IFN-gamma but no IFN-alpha. Since IFN-alpha but not IFN-gamma is produced by monocytes it is likely that reduced numbers of monocytes which were found in our HCL patients before and during IFN treatment account for the described deficiency of IFN-alpha production.

Breast Neoplasms↗
PubMed1986

Conversion of acute undifferentiated leukemia phenotypes: analysis of clonal development.

The cellular origin of acute undifferentiated leukemia (AUL) is still a matter of controversy. We report on two cases in which the diagnosis of AUL was established according to restricted criteria. Blast cells of both patients showed phenotypic conversion during the course of disease. In one case, within 24 days from starting treatment, the leukemic phenotype changed from AUL to acute myelomonocytic leukemia (FAB L1, TdT+ to FAB M4, TdT-). The initial phenotype of this acute leukemia was characterized by the co-expression of both B-lymphoid and myeloid markers on the same cell. Moreover, analysis of esterase isoenzyme pattern showed the whole spectrum of isoenzymes typically seen in myelomonocytic leukemias already at diagnosis, yet blast cells additionally contained all three isoenzymes of beta-hexosaminidase typically seen in AUL. However, examination of immunoglobulin (Ig) heavy chain gene rearrangement initially and after conversion revealed an identical monoclonal configuration of Ig heavy chain sequences in both samples. The second AUL patient relapsed after allogeneic bone marrow transplantation with common ALL-antigen (CALLA) positive acute leukemia. Subsequent Southern blot analysis showed a novel rearranged Ig fragment compared to the analysis before transplantation indicating that the leukemic clones prior to and after transplantation were not identical. No chromosomal abnormalities were observed in both cases. These data support the view that AUL cells originate from a pluripotent stem cell that is capable to differentiate in the myelomonocytic lineage (patient 1), and confirm the value of Ig gene analysis as marker for cellular clonality.

Adult↗
PubMed1986

TAD-induction therapy for 175 adults with acute myeloid leukemia, followed by consolidation and maintenance therapy. The joint study of Ulm and Tübingen.

175 patients with acute myeloid leukemia were treated between February 1980 and March 1985 with a TAD-induction therapy, three intensified consolidation cycles (COAP, COAP, AD), and a two-year mild maintenance therapy. The median age of the patients was 44 years, range 15-68 years. 62.3% of all patients attained complete remission and 13.7% partial remission. The median duration of remission was 10 months and the median survival time of patients in complete remission was 20 months. Patients older than 50 years had a higher early death rate (17.6) than younger patients (8.9%), but no difference was found in remission rates or in the median duration of remission and of survival. These results are in line with those of comparable studies.

Adolescent↗
PubMed1986

Age adapted induction and intensified consolidation therapy in acute myelogenous leukemia.

52 patients entered a study for remission induction and intensified consolidation in AML. Group I (age less than or equal to 50 years) received a combination of DNR, ara-C and VP16-213 for induction and early consolidation and HDara-C/DNR for late consolidation. Of 34 evaluable patients (25 first diagnosis, 9 first relapse), 27 achieved CR. 13 patients received 1-2 courses of HDara-C/DNR. Toxic symptoms of HDara-C/DNR were severe myelosuppression, infections, skin reactions, diarrhea and hepatotoxicity. CNS toxicity was not observed. 2 patients died from infection. The duration of granulocytopenia (less than 500/microliter) was 7-43 days (range) and of thrombocytopenia (less than 25,000/microliter) 5-34 days (range). Patients of group II (age greater than 50 years) received a modified regimen with reduced toxicity. Their number is too small for evaluation as yet.

Aclarubicin↗
PubMed1986

Acute undifferentiated leukemia: implications for cellular origin and clonality suggested by analysis of surface markers and immunoglobulin gene rearrangement.

Although B cell leukemias and, recently, T cell leukemias can be identified both by surface marker and molecular analysis, there remains a population of acute undifferentiated leukemias (AUL) that cannot be allocated definitively to a single cell lineage. AUL was diagnosed in nine patients according to stringent criteria. We combined both immunologic and molecular approaches to analyze further the ambiguous origin of AUL cells. Southern blot analysis revealed rearranged Ig heavy-chain genes in seven patients and indicated a biclonal or oligoclonal leukemic cell population in three of them, including one case of AUL with translocation (4;11). Analysis of cell surface markers showed expression of at least one early B cell-associated antigen (BA-1, BA-2, B4, UL-38) in six of these seven patients, with coexpression of a myeloid antigen (VIM-2) in three patients. Leukemic cells of two other patients neither exhibited Ig chain gene rearrangements nor expressed B cell-associated antigens. T cell receptor beta-chain genes showed germline configuration in all nine cases. Our results demonstrate heterogeneity among AUL patients based on molecular and surface marker analyses and suggest that most AUL blast cells are derived from a precursor cell that shares phenotypic and genotypic characteristics of early B cells with certain surface antigens of myeloid cells, in some cases of AUL more than one abnormal cell clone or subclone may exist, and the cellular origin, at least of some AULs exhibiting t(4;11), may be truly B cell lineage committed.

Antibodies, Monoclonal↗
PubMed1986

[Indomethacin in the treatment of ureteral colic caused by calculi].

Experiences are reported in the therapy of recurrent colics caused by ureteroliths. In 41 patients an initial treatment with indomethacin suppositories was performed which led to a removal of the colics in 37 patients. A comparative group of 46 patients was conventionally treated by means of an injection therapy of analgin/papaverin. In order to achieve painlessness, on a average 10 to 15 injections were necessary during the hospital treatment. The importance of the indomethacin therapy described lies in the possible self-application by the patient as well as in the avoidance of recurrent colics, frequent consultations of emergency physicians and hospitalisations.

Adolescent↗
PubMed1985

[High-dose cytosine arabinoside in the treatment of recurrent or acute refractory myeloid leukemias].

10 adult patients (age 27-62 years) with refractory or relapsed acute nonlymphocytic leukemia were treated with high dose cytosine arabinoside (HDAraC: 3 g/m2 q 12 h by IV infusion, d 1-6) either alone (7 patients) or with additional treatment, consisting of bone marrow transplantation (1 patient), m-AMSA (1pt.) and VP16 (1 patient). All patients had received conventional dose AraC (CDAraC); 8 patients were resistant to CDAraC, having failed 1 or more courses of CDAraC just before treatment with HDAraC. Recovery of granulocyte count (0,5 X 10(9)L) occurred at a median of 26 d (23-27 d) after initial therapy, and recovery of platelet counts (50 X 10(9)/L) at a median of 24 d (22-27 d). 6 patients became severely septic, 3 of them requiring granulocyte transfusions. Consequently, sophisticated blood banking facilities and supportive care are required. The non-myeloid toxicities associated with HDAraC were not severe. Vomiting (9/10), erythematous skin rash (4/10), conjunctivitis and photophobia (2/10) were found most commonly. CNS-toxicity, pulmonary toxicity or drug fever were not observed. 4 patients achieved a complete remission and 1 a partial remission. 2 patients failed to respond and 3 patients died during the period of pancytopenia. Thus, HDAraC is effective treatment for refractory or relapsed ANLL, even in cases of apparent resistance to CDAraC.

Adult↗
PubMed1984

Genetic resistance to Leukosis virus infection: effects on mortality and egg production in Leghorn hens.

The influence of genotypic differences in resistance to infection from Lymphoid Leukosis (LL) on mortality and egg production was studied in three pairs of sublines. One subline of each pair had been selected for resistance and the other for susceptibility to infection. At 10 months of age, almost no hens with neutralising antibodies against LL were found in the resistant sublines, while in each susceptible subline more than 40% of the hens had LL antibodies. At 21 months of age, very few hens of the resistant sublines had group-specific (gs) antigen in their eggs. Susceptible sublines differed considerably in this respect, from 81% gs antigen-positive hens in one subline to 9% or no positive hens in the others. On the whole, the susceptible sublines had 6% higher mortality during the laying period (8 months) but the size of the difference was influenced by vaccination against Marek's disease (MD) and varied considerably between pairs of sublines. Significant interactions between strain and genotype of resistance to LL infection were observed for mortality from "other causes" in hens vaccinated against MD, as well as for mortality from "Leukosis" and from "MD" in non-vaccinated hens. The average rate of lay from 1 to 8 months was 8% lower in susceptible hens. In the subline with the highest frequency of eggs containing LL group-specific antigen in the albumen, the reduction of laying rate was twice as large as in the other susceptible sublines.

Animals↗
PubMed1982

[Intravital diagnosis of left-atrial tumors--a clinical problem].

It is reported on a myxoma of the left atrium in a 44-year-old female. A diagnosing of the tumors intra vitam was not successful, the patient died under the signs of the severe apoplectic insult. Autoptically the myxoma with multiple arterial embolisation was proved. The author deals with the difficulties of diagnosing in life-time, the clinical main symptoms of atrial tumours and differential-diagnostic viewpoints are mentioned. As a matter of principle a successful diagnosis and therapy in this disease are nowadays possible, the importance of thinking of that fact in adequate symptomatology is emphasized.

Adult↗