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Biomedical subjects

R Berger

Publications and source records attributed to R Berger.

At least 343 records · Page 19Linked to original sources
PubMed1994

Myelosuppression in HCL: role of hairy cells, T cells and haematopoietic growth factors.

To elucidate mechanisms which may be responsible for the haematopoietic insufficiency in hairy cell leukaemia (HCL), we investigated in an autologous in vitro system the influence of haematopoietic growth factors (CSFs) and the effects of hairy cells (HCs) as well as T cells on the formation of haematopoietic colonies (CFU). Colony forming assays were performed using peripheral blood mononuclear cells (PBMC) of 6 HCL patients. To remove HCs, PBMCs were subjected to complement-mediated lysis, T cells were removed by E-rosette formation. Assays were done with and without recombinant human (rh) interleukin-3 (IL-3) and rh granulocyte-macrophage-colony-stimulating factor (GM-CSF). All 6 patients exhibited a severe reduction of their circulating progenitor cell (CPC) compartment. There was no correlation between the degree of colony reduction and the number of HCs. However, a correlation was found between the numbers of CPCs of HCL patients and healthy donors and the monocyte counts in these groups (r = 0.8573, p < 0.001). The removal of autologous HCs, but also of T cells, resulted in a significant increase in colony formation (BFU-E, CFU-GM, CFU-mix). In none of the experiments, however, did colony numbers come close to the normal range. This was only achieved by supplementation of the culture medium with rh IL-3 and rh GM-CSF. The results suggest that the haematopoietic failure observed in HCL patients is probably due to an inadequate supply of CSFs as well as to an inhibitory activity of HCs and T cells which might exert their effects in a synergistic fashion. There is also evidence that the lack of monocytes plays a role in the development of the haematopoietic insufficiency in HCL.

Adult↗
PubMed1994

Effects of nortriptyline on heart rate variability in panic disorder patients: a preliminary study using power spectral analysis of heart rate.

Previous reports on heart rate variability suggest that, compared to controls, panic disorder patients have a higher relative mid-frequency (MF) (0.07-0.15 Hz) power in standing posture and that they also have a greater increase in standing MF power after the administration of yohimbine. We studied the effects of nortriptyline, a tricyclic antidepressant, on HR variability measures in 13 panic disorder patients before and after successful treatment. There was a highly significant increase in supine and standing HR (p = 0.00001) while there was a significant decrease of standing absolute and relative MF power (p = 0.009 and 0.0001 respectively). This uncontrolled preliminary study suggests a decrease in sympathetic activity related to nortriptyline treatment in addition to its anticholinergic effects.

Adult↗
PubMed1994

Self-induced correction of the genetic defect in tyrosinemia type I.

A mosaic pattern of immunoreactive fumarylacetoacetase (FAH) protein was found in liver tissue in 15 of 18 tyrosinemia type I patients of various ethnic origins. One additional patient had variable levels of FAH enzyme activity in liver tissue. In four patients exhibiting mosaicism of FAH protein, analysis for the tyrosinemia-causing mutations was performed in immunonegative and immunopositive areas of liver tissue by restriction digestion analysis and direct DNA sequencing. In all four patients the immunonegative liver tissue contained the FAH mutations demonstrated in fibroblasts of the patients. In the immunopositive nodules of regenerating liver tissue one of the mutated alleles apparently had reverted to the normal genotype. This genetic correction was observed for three different tyrosinemia-causing mutations. In each case a mutant AT nucleotide pair was reverted to a normal GC pair.

Amino Acid Metabolism, Inborn Errors↗
PubMed1994

Soluble CD23 reliably reflects disease activity in B-cell chronic lymphocytic leukemia.

PURPOSE: This study was initiated to evaluate whether soluble CD23 (sCD23) reflects disease activity and tumor load in B-cell chronic lymphocytic leukemia (B-CLL) and to determine its prognostic potential for this disease. PATIENTS AND METHODS: The concentration of sCD23 was measured in the serum of 45 B-CLL patients, 50 patients with other lymphoproliferative disorders, and 41 healthy donors (HD). sCD23 serum levels from B-CLL patients were correlated with parameters of disease activity and total tumor mass (TTM) score. In selected cases, sCD23 was measured repeatedly over a 24-month period. Expression, density, and calculated total amount of membrane CD23 on peripheral-blood B-CLL cells, as well as its correlation to sCD23 levels in serum and supernatants, were determined. RESULTS: sCD23 in B-CLL patients serum was highly elevated as compared with other lymphoproliferative disorders, with the exception of immunocytoma (IC). Both advanced Rai stages and active forms of B-CLL were associated with higher levels of sCD23. There was a highly significant reciprocal relationship between sCD23 and lymphocyte count doubling time (LCDT). Serum sCD23 correlated positively with serum deoxythymidine kinase activity and TTM score, but not with absolute lymphocyte counts. The repetitive measurement of serum sCD23 showed the usefulness of this marker in monitoring disease progression in B-CLL. The total amount of membrane CD23 on in vitro-cultured B-CLL cells correlated significantly with sCD23 levels in the supernatant, whereas correlation between serum sCD23 and membrane CD23 on freshly isolated B-CLL cells was absent. CONCLUSION: Our results indicate that sCD23 is a highly sensitive and specific parameter with prognostic potential for B-CLL, which may be used as a tumor marker and may help to assess disease activity.

Biomarkers, Tumor↗
PubMed1994

Survival after in-hospital cardiopulmonary arrest of noncritically ill patients. A prospective study.

BACKGROUND: The rising healthcare costs and the ethical and economic implications of cardiopulmonary resuscitation (CPR) have generated interest in defining criteria to predict the appropriateness of CPR in specific patients. Age has been proposed as one such a criterion. METHODS: As part of a quality assurance program, all instances of CPR (code-500) at our VA Medical Center were prospectively studied over a period of 45 months. Only events in noncritical care hospital areas were included in this analysis. The CPR data were prospectively collected, and follow-up of initial survivors was continued until the end of the study period or until a patient died. RESULTS: Of a total of 422 code-500 events, 387 (92 percent) met our study definition of cardiorespiratory arrest, and 255 of these occurred in a noncritical care area and were included in the study. Our immediate survival was 52 percent (n = 132), survival after intensive care unit (ICU) stay was 22 percent (n = 55), survival to hospital discharge was 11 percent (n = 28), and 4 percent of the patients (n = 10) were alive at the end of follow-up (mean, 22 months). None of the patients discharged alive had a significant new neurologic deficit, and all but one returned to their preadmission environment. The post-CPR hospital charges for each of the surviving patients was estimated at $63,000. Age, the admitting diagnosis, and main comorbidity did not predict long-term survival. The post-CPR Apache II score correlated with a patient surviving the ICU stay, but did not correlate with long-term survival either. CONCLUSIONS: Age alone is not a valid criterion to decide whether a patient is a suitable candidate for CPR, and the principal diagnosis and main comorbidity at the time of admission do not appear to predict long-term survival either. Whether in-hospital CPR in noncritical care areas is cost-effective is an issue that society at large must eventually decide.

Adult↗
PubMed1994

AML-1 gene rearrangement and AML-1-ETO gene expression as molecular markers of acute myeloblastic leukemia with t(8;21).

Rearrangements of the AML-1 gene on chromosome 21 as well as transcriptional expression of AML-1-ETO fusion gene were studied in 35 leukemic patients with t(8;21)(q22;q22). A panel of probes generated from the AML-1 gene regions flanking the breakpoint on chromosome 21 allowed us to detect the rearrangement in 24 out of 29 patients. A specific nested reverse transcriptase/polymerase chain reaction (RT/PCR) was developed to detect the t(8;21), either at diagnosis or as minimal residual disease. PCR amplification products were obtained in ten out of 11 patients investigated, and the sensitivity of the reaction was estimated to be between 1 x 10(4) and 1 x 10(-5) cell. An AML-1 rearrangement was also detected in one patient with 8q- and only one chromosome 21, but without 21q+. This indicated that the molecular rearrangement of the der(8) chromosome is more important than the reciprocal one in the malignant process.

Adolescent↗
PubMed1994

Distinct MLL gene rearrangements associated with successive acute monocytic and lymphoblastic leukemias in the same patient.

A patient with acute monocytic leukemia (AMoL) and t(6;11)(q27;q23) developed acute lymphoblastic leukemia (ALL) and t(4;11)(q21;23), 10 months after complete remission of the AMoL. The MLL gene, normally located at band 11q23, appeared differently rearranged in the cells of these two leukemias, showing a different origin for the two malignant clones. The responsibility of etoposide, used in treatment of the AML, in the occurrence of the ALL is probable in this patient.

Adult↗
PubMed1994

Alterations of the putative tumor suppressor gene p16/MTS1 in human hematological malignancies.

The chromosome band 9p21-22 is frequently rearranged or deleted in a variety of tumors including hematological malignancies. This supports the notion of a tumor suppressor gene in this chromosome region. Indeed, the p16/MTS1 gene encoding a cyclin-dependent kinase (CDK) inhibitor has been shown to be frequently deleted and/or inactivated by nonsense mutations in a number of tumors. We have examined 98 DNA samples from blood, bone marrow cells and lymph node biopsies of patients with leukemia (ALL and AML) or lymphoma (follicular lymphoma and T-cell lymphoma), using Southern blot hybridization and a p16/MTS1-specific probe. Molecular abnormalities, mainly homozygous deletions, were found principally in ALL (8 out of 22 patients), much less frequently in AML (2/32) and lymphoma (2/32). While these data argue in favor of a large involvement of p16/MTS1 in ALL, AML and lymphomas appear to be less frequently implicated.

Adult↗
PubMed1994

Hereditary tyrosinemia type I: a new clinical classification with difference in prognosis on dietary treatment.

Hereditary tyrosinemia type I (McKusick 27670) is a heterogeneous disease with poor prognosis, yet there are few reports of the long-term prognosis. It is therefore difficult to decide on the treatment for individual patients. We have conducted an international survey of patients with tyrosinemia type I and examined the probability of survival on dietary treatment and the causes of death in 108 patients with tyrosinemia type I. The survival after the onset of symptoms varied with the age at onset; the earlier the symptoms developed the poorer the outlook. Liver failure and recurrent bleeding (67%), hepatocellular carcinoma (17%) and the porphyria-like syndrome with respiratory failure (10%) were the most common causes of death. The 1- and 2-yr survival probability after the onset of symptoms in patients in whom symptoms developed before 2 mo, between 2 and 6 mo and after 6 mo were 38%/29%, 74%/74% and 96%/96%, respectively. On the basis of these survival rates, a new classification--which is important with respect to choices in treatment--is proposed: very early (onset of symptoms < 2 mo), early (2 to 6 mo) and late presenting form (> 6 mo).

Cause of Death↗
PubMed1994

Translocation t(11;11)(q13;q23) and HRX gene rearrangement associated with therapy-related leukemia in a child previously treated with VP16.

A child with acute myelomonocytic leukemia, bone marrow eosinophilia and inv(16) received first-line therapy including etoposide (VP-16). Cytopenia and monocytosis appeared 7 months after complete remission while the child was treated with maintenance chemotherapy. Blood abnormalities persisted after discontinuation of treatment. Nine months after complete remission, t(11;11)(q13;q23) and HRX rearrangement were detected. Five months later, overt leukemia of monocytic type occurred. The responsibility of VP-16 therapy in this treatment-related acute myelocytic leukemia is discussed.

Adolescent↗
PubMed1994

Novel splice, missense, and nonsense mutations in the fumarylacetoacetase gene causing tyrosinemia type 1.

In six unrelated patients with hereditary tyrosinemia type 1 (HT1), three different disease-causing mutations were found by DNA sequencing. Two Pakistani patients, with acute and intermediate forms of HT1, were homozygous for a G192-->T mutation in the last nucleotide of exon 2. This caused aberrant splicing with partial intron 2 retention and premature termination. Three Turkish patients with chronic and intermediate forms of HT1 were homozygous for an A698-->T mutation substituting aspartic acid 233 with valine. A Norwegian patient with an intermediate clinical phenotype was heterozygous for G786-->A, introducing a TGA stop codon for Trp262 (W262X). Site-directed mutagenesis and expression in a rabbit reticulocyte lysate system demonstrated that the nonsense and missense mutations abolished fumarylacetoacetase activity and gave reduced amounts of a truncated and a full-length protein, respectively. Simple tests were established to identify the three mutations by restriction digestion of PCR-amplified genomic DNA. Among 30 additional HT1 patients investigated, 2 were found to be homozygous and 1 heterozygous for G192-->T. Two other patients were homozygous and one was heterozygous for W262X.

Alternative Splicing↗
PubMed1994

[Intra- and postoperative nerve lesions and their treatment].

Injuries to the central or peripheral nerves caused by medical intervention are called iatrogenic nerve lesions. The caudal relationship between medical intervention and iatrogenic nerve injuries is frequently not very clear. Careful pre- and post-operative examination of the patient, however, will in most instances reveal a nerve lesion in a timely manner. Iatrogenic nerve lesions in the clinical cases available to us were predominantly due to indirect influences, such as pressure, insertion of a retractor or heat; we discovered that only in a few cases a nerve was partially or completely severed or damaged by the material used for osteosynthesis. The pre- and postoperative clinical neurological and electrophysiological examinations of our patients were performed by a neurologist. Nerve-repair was achieved by neurolysis in 19 cases; a primary or secondary suture was performed in three cases. A nerve graft was used in five cases to regain continuity. Those patients (nearly 75%) who underwent restitutive surgery within an six-month period after iatrogenic injury in the primary operation were treated successfully. These results suggest that timely treatment is decisive for good outcome.

Adolescent↗
PubMed1994

A novel gene, AF-1p, fused to HRX in t(1;11)(p32;q23), is not related to AF-4, AF-9 nor ENL.

Most of the translocations affecting the chromosome band 11q23, frequently seen in human acute leukemias, involve a restricted area of the HRX gene. We have characterized two t(1;11)(p32;q11) translocations which fuse the HRX gene to a novel gene, AF-1p on chromosome 1p32, in two myeloid leukemias. The der (11) chromosome expresses the 1368 N-terminal amino acids of HRX, including the AT-hook, snRNP and methyltransferase similarities, fused to almost all the AF-1p product. The predicted wild type AF-1p product is a 98 kDa acidic protein which does not exhibit similarity to the AF-4, AF-9 and ENL gene products. It is highly similar to the murine eps 15 gene product, which encodes a cytoplasmic phosphoprotein. Our data indicate that AF-1p defines another class of genes fused to HRX in 11q23 abnormalities.

Adaptor Proteins, Signal Transducing↗
PubMed1994

Hunting 11q23 deletions with fluorescence in situ hybridization (FISH).

Seven patients with acute leukemia and translocation involving band 11q23 have been studied by fluorescence in situ hybridization (FISH) using YAC probes spanning the HRX gene. While hybridization signal was split by translocation between the rearranged 11 and the partner chromosomes in five patients, only one signal on the derivative 11 was observed in two patients, one with t(9;11)(p21-22;q23) and the other with t(6;11)(q27;q23). Having shown that HRX was rearranged in these two cases, the distal part of 11q23 was investigated using other YACs containing markers for this region. This showed that a 600-700 kb deletion, distal to the HRX breakpoint cluster region, had occurred in the two cases. This study supports the notion that the 5' end of HRX is the important part in the chimeric genes resulting from 11q23 translocations and suggests that deletions of the 3' part are not uncommon.

Adult↗
PubMed1994

Translocation t(8;21)(q22;q22): cytogenetics and molecular biology.

The t(8;21)(q22;q22) translocation, usually present with a subtype of acute myeloblastic leukemia with maturation in young patients, is associated with other chromosome abnormalities in about 75% of the cases. These secondary changes are mainly loss of sex chromosome (X in 41% of females and Y in 61% of males). The genes rearranged by t(8;21), named AML-1 on 21 and ETO on 8, were recently identified. AML-1 shows homology with the Drosophila segmentation gene runt and ETO with cyclin D2. The chromosomal breakpoints are clustered within introns of the two genes and t(8;21) results in a fusion gene that makes possible the detection of translocation by polymerase chain reaction (RT-PCR).

Chromosomes, Human, Pair 21↗