[Multidrug resistance in lymphoproliferative syndromes].
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ATP Binding Cassette Transporter, Subfamily B, Mem↗
Biomedical subjects
D Damiani
Publications and source records attributed to D Damiani.
[Multidrug resistance in acute nonlymphoid leukemia].
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ATP Binding Cassette Transporter, Subfamily B, Mem↗
In vitro bone marrow purging of multidrug-resistant cells with a mouse monoclonal antibody directed against Mr 170,000 glycoprotein and a saporin-conjugated anti-mouse antibody.
Selective elimination of multidrug resistance-positive cells (LoVo/Dx) was obtained by using the monoclonal antibody MRK 16, which recognizes a surface epitope of the Mr 170,000 glycoprotein, and a sheep anti-mouse immunoglobulin antibody, conjugated to the ribosome-inactivating protein saporin 6. The killing was greatly decreased or even abolished by adding the monoclonal antibody at a 100-fold concentration. Both the MRK 16 and anti-mouse saporin 6 conjugate did not show any killing activity when they were used separately. In cell suspensions composed of 90% normal bone marrow cells and 10% multidrug resistance-positive cells, the monoclonal antibody MRK 16 followed by the anti-mouse immunotoxin caused the elimination of 99% multidrug resistance-positive cells, as revealed by immunofluorescence and immunocytochemistry as well as by a clonal assay. Human normal hematopoietic precursors (granulomonocytic colony-forming units, erythroid burst-forming units, and multipotent granulomonocytic, erythroid, and megakaryocytic-forming units) were not affected by the MRK 16 plus immunotoxin treatment. This technique might be suitable for ex vivo bone purging in an appropriate clinical setting, such as autologous bone marrow transplantation.
Antibodies, Monoclonal↗
Investigation of the ZFY gene in XX true hermaphroditism and Swyer syndrome.
Four patients with 46,XX true hermaphroditism and one patient with 46,XY pure gonadal dysgenesis (Swyer syndrome) were analyzed with a Y chromosome-derived probe that detects a specific fragment on the short arm of the Y chromosome in the putative testicle-determining region and also a fragment on the short arm of the X chromosome. Normal males and females, an individual with Turner syndrome, and patients with various causes of anomalous gonadal differentiation accompanied by cytogenetically present Y chromosome were used as controls. The Y-specific fragment was not detected in any of the persons with 46,XX true hermaphroditism. However, this fragment was positive in the 46,XY female and in all Y-bearing patients. Cytogenetic and molecular absence of the ZFY sequence in 46,XX true hermaphrodites calls for explanations other than the classic embryogenic theory. The absence of testicular differentiation in the ZFY-positive XY female evidences functionally altered sex determination or, alternatively, defective gonadal receptors.
Adolescent↗
Comparison between the L-DOPA histofluorescence procedure and the indirect immunofluorescence with anti-T6 and -HLA-DR monoclonal antibodies in visualizing Langerhans cells of human epidermis.
In order to assess the reliability of the L-DOPA histofluorescence (HF) procedure in visualizing the Langerhans cells (LC) of human epidermis, serial sections of human normal skin samples have been incubated with L-DOPA and alternatively processed for the L-DOPA HF and the indirect IF with anti-T6 and anti-HLA-DR monoclonal antibodies. Results demonstrated a good correlation of LC labelling; comparison between the number of L-DOPA positive (T6 positive and L-DOPA positive) HLA-DR positive dendritic cells did not show statistically significant differences. Therefore, the L-DOPA HF represents a valuable method for detecting LC in the human normal epidermis.
Adult↗
Treatment of Ph+ chronic myeloid leukemia by gamma interferon.
The clinical, hematologic and cytogenetic effects of human recombinant gamma interferon (IFN) were investigated in 14 patients with Ph+ chronic myeloid leukemia (CML). Gamma-IFN was given at a daily dosage of 0.50 mg (= 10 x 10(6) U)/m2 from the 3rd week of treatment on, but the dosage had to be reduced to 0.25 mg/m2 in 10 cases and to 0.35 mg/m2 in 2 cases, because of the severity and persistence of side effects (mainly fever, fatigue, headache and pain). Only 2 patients tolerated the full dosage. The overall response rate was 64% (1 complete and 8 partial hematologic responses). Only patients in stable chronic phase responded. Two out of two patients in unstable chronic phase and two out of two patients in accelerated phase failed to respond. Eight out of nine responding patients remained in remission throughout the duration of treatment (30 to 35 weeks). No karyotypic conversion was detected. These data show that gamma IFN alone is effective in Ph+ CML, but that side effects can limit substantially the dosage and duration of treatment.
Adult↗
Sensitivity of Ph 1 + CFU-GM to human recombinant interferon alpha and gamma alone and in combination.
The in vitro effect of human recombinant interferon alpha (IFN) alone and in combination were studied on granulomonocytic colony forming units (CFU-GM) from the peripheral blood of 10 Ph 1+ chronic myeloid leukemia (CML) patients and from the marrow of 5 normal or non-leukemic subjects. alpha- and gamma-IFN alone determined a slight inhibition on colony growth with a preferential effect on "pure" macrophagic colonies. At maximum concentration (10(4) U/ml) leukemic colony inhibition was 46 +/- 34% for alpha IFN and 43 +/- 19% for gamma IFN. Culture growth with alpha + gamma IFN in combination were significantly inhibited (up to 96 +/- 4%) with a concentration-related effect. Similar results were obtained with normal CFU-GM. The synergism that was found in vitro is probably relevant for the in vivo therapeutic effects of these compounds in CML and suggest that the combination is worth testing in vivo.
Drug Therapy, Combination↗
Interferon gamma in chronic myeloid leukemia: dose and side effects.
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Drug Administration Schedule↗
Cell kinetic effect of low dose arabinosyl cytosine.
Low dose arabinosyl cytosine (ARA-C) is effective for treatment of acute non-lymphocytic leukaemia (ANLL). The mechanism of action is not clearly understood and it was suggested that low doses of the drug could induce leukaemic cells to differentiate. We investigated the effect of low dose ARA-C (20 mg/m2/d, divided into two doses s.c. at 12 h intervals, x 20 d) on the cell cycle distribution of leukaemic cells in four cases of ANLL. By comparison, four other cases of ANLL were studied during treatment with standard dose ARA-C (200 mg/m2/d as a continuous i.v. infusion x 7 d). Both treatments induced an accumulation of leukaemic cells in post G1 phases, at a variable extent and rate. During treatment by low dose ARA-C, the mitotic index (MI) fell slowly to zero in two patients who achieved a complete remission (CR), while it fell but recovered during treatment in the patients who did not achieve a CR. The MI fell rapidly to zero in the four cases treated by standard dose, who achieved a CR. These data are consistent with the known cytotoxic activity of ARA-C, via inhibition and slowing of DNA synthesis leading to defective cell proliferation and to cell death.
Acute Disease↗
[Side effects of d-penicillamine in the treatment of rheumatoid arthritis].
In the present study, the side effects of d-Penicillamine therapy in 54 patients with rheumatoid arthritis are analyzed. The therapeutic efficacy of the drug is emphasized; but in the meantime, the necessity is also stressed that the choice of this antirheumatic agent must imply the knowledge of the possible complications caused by its use and of the clinical features and laboratory data which would be useful for their early detection.
Adult↗
[Reinforced resins or composites].
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Composite Resins↗
Proliferating cell nuclear antigen immunoreaction in adrenal tumors.
AIMS AND BACKGROUND: We studied, retrospectively, 33 cases of adrenal tumors of children at the Pediatric Endocrinology Unit, Children's Institute, São Paulo State University Medical School, from 1975 to 1993. All patients had at least 2 years of follow-up with a few exceptions. METHODS: Clinical follow-up data were correlated with histopathologic review, laboratory data and cell kinetic evaluation (based on detection of proliferating cell nuclear antigens). RESULTS: With one exception, all the patients had presented signs of androgen production and had high levels of dehydro-epiandrosterone-sulfate. Tumor weight evaluation represented a good parameter of neoplasm evolution: of 19 cases weighing less than 250 g, 17 had no evidence of disease after surgery, and 2 had an unfavorable prognosis. Of 14 cases weighing more than 250 g, only 1 had no evidence of disease and 13 had an unfavorable evolution. CONCLUSIONS: Proliferating cell nuclear antigen (PCNA) was not helpful to evaluate adrenal neoplasm evolution: our study did not show any correlation between PCNA score and prognosis.
Adrenal Gland Neoplasms↗
Serum lactate dehydrogenase fails to predict response to treatment and survival in acute non-lymphocytic leukemia.
Total serum lactate dehydrogenase (LDH) activity was measured in 514 adult patients with de novo acute non-lymphocytic leukemia (ANLL) prior to any treatment and was compared with several disease features, with response to induction treatment, and with relapse-free survival. LDH was higher in the M4 and M5 FAB cytological subtypes and was positively correlated with the white blood cell count (WBC). The proportion of remissions, of deaths during induction, and of failure, and the duration of relapse-free survival, were clearly unrelated to LDH activity, in the whole series as well as in different age groups (below 40 years, and 40 to 60 years) and in any FAB cytological subtype. Multivariate analysis showed that only WBC and sex (female better than male) were marginally related with relapse-free survival. These data provide conclusive evidence that LDH does not help in defining the prognosis of adult ANLL, either because enzyme activity fails to reflect the number and proliferation rate of leukemic cells efficiently, or because with current standard treatment these features are of borderline importance, in contrast with acute lymphocytic leukemia and malignant lymphomas.
Adolescent↗
Primary hyperparathyroidism in children: patient report and review of the literature.
Although primary hyperparathyroidism has rarely been described in pediatric patients, prompt diagnosis can avoid severe CNS and metabolic consequences. The aim of this paper is to report a 6 year-old girl whose first symptoms began at eight days of age with cyanosis, hypotonia, and upward gaze deviation. At 4 months, she was admitted due to neurologic disorders and recurrent infection, but the definite diagnosis was made only six years later. Her serum calcium levels are among the highest ever reported in the medical literature, reaching 25.5 mg/dl (6.36 mmol/l). Hypercalcemia, very high levels of parathormone (1550 ng/l--normal range 10-65) and bone deformities posed no problem to diagnosis when she first came to our attention. Nephrocalcinosis and impaired renal function were detected and this child had to be treated with diuretics (furosemide) and hydration that were able to lower her serum calcium levels. Imaging studies including 99mTc-sestamibi scan were not diagnostic. At surgery, the four parathyroid glands were mildly enlarged, with primary hyperplasia. The four glands were removed, cryopreserved, and 14 fragments (1 mm each) were autotransplanted to the braquioradial muscle of the left forearm. After a first phase of hypocalcemia (hungry-bone syndrome), treated with calcium and calcitriol, the calcium levels stabilized. The question is whether she will experience some degree of recovery from her neurological problems, since her severely high calcium levels have been maintained for such a long time.
Age of Onset↗
Pituitary macroadenoma and Cushing's disease in pediatric patients: patient report and review of the literature.
Cushing's syndrome in pediatric patients has been rarely reported and most of the cases are due to adrenal tumors. When the etiology is an ACTH-secreting pituitary adenoma, most often it is a microadenoma. We report on a 9 year-old girl with an ACTH-secreting macroadenoma, whose surgical removal through transsphenoidal approach was extremely difficult due to invasion of the cavernous sinus as well as adjacent structures. After two surgical approaches and stereotactic radiotherapy, she still suffers from the deleterious effects of hypercortisolism, especially marked osteoporosis with vertebral collapse, which interferes with her walking and causes excruciating pain. Two months after the radiotherapy, we still had doubts about the prognosis regarding the persistence of the hypercortisolism. From six months on, her general health started improving, she lost weight, the backache disappeared and her cortisol level returned to normal.
Adenoma↗
Ullrich-Turner syndrome: relevance of searching for Y chromosome fragments.
Forty consecutive patients with Ullrich-Turner syndrome (UTS) were followed-up and investigated for the presence of Y chromosome fragments in their genomes. We used the polymerase chain reaction (PCR) to detect SRY (sex-determining region on the Y chromosome) and the sequence-tagged sites (STS) sY57, sY59, sY85, sY94, sY124 and sY157--which correspond to regions 3C (sY57 and 59), 5C, 5G, 5P, and 6F, respectively, of the Y chromosome--searching for Y fragments that could bear the putative locus (loci) for gonadoblastoma (GBY). It has been shown that the presence of GBY greatly increases the risk of dysgenic gonads to undergo malignant transformation. Among our 40 patients, we found Y-derived sequences--including SRY and the region spanning from sY57 to sY94--in two. These two patients had a marker chromosome detected by conventional cytogenetic analysis (45,X/46,X + mar). Their gonads were excised and found to be streaks. In one of the patients, we found foci of primitive sex cords (amidst the gonadal stroma), oviducts and Wolffian remnants. Fluorescence in situ hybridization (FISH) did not show Y chromosome material in her gonad-derived fibroblasts. The other girl had hyperplastic Leydig cells in the gonadal stroma, oviducts and Wolffian remnants, with signs of epididymal differentiation. PCR assays performed on DNA extracted from paraffin-embedded gonadal tissue were negative for SRY sequences in both patients. These findings show that all UTS patients should be examined for Y chromosome material, and that positive cases should have their dysgenic gonads excised due to the high risk of malignancy.
Base Sequence↗
Persistence of Müllerian remnants in complete androgen insensitivity syndrome.
One of the unusual findings in androgen insensitivity syndrome (AIS) is the persistence of Mullerian derivatives. Several hypotheses have been advanced to explain such persistence: the coincidental occurrence of mutations affecting the androgen receptor (AR) and the synthesis and/or action of anti-Müllerian hormone (AMH); the loss of AMH paracrine action due to early testicular descent; the exposure to drugs such as diethylstilbestrol. We describe a patient with complete AIS for whom surgical and laboratory findings rule out all these hypotheses. She has a missense mutation on the AR gene but no mutations were detected on the genes coding for AMH and AMH receptor. The gonads were found very close to the Mullerian structures (enough to exert a paracrine action), gonadal tissue stained positively for AMH, and yet Mullerian derivatives were present and well developed. These findings indicate the possibility of interactions between the androgen receptor and AMH action.
Adolescent↗