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Biomedical subjects

M Bonno

Publications and source records attributed to M Bonno.

9 recordsLinked to original sources
PubMed1998

Thrombopoietin level is inversely related to blast count, not platelet number, in Down syndrome neonates with transient myeloproliferative disorder.

Transient myeloproliferative disorder (TMD) in neonates with Down syndrome is characterized by increased megakaryoblastic cells in the peripheral blood. Despite their spontaneous regression in weeks, prognosis is not always favorable because of fatal hepatic fibrosis. In this study, blood thrombopoietin (TPO) levels were measured by ELISA in six TMD patients and the expression of c-Mpl, a ligand for TPO, was examined on the blast cells from four patients by flow cytometer. At the onset, TPO level was undetectable in one patient and significantly lower in five patients than six neonatal controls (mean 0.52 fmol/ml, range 0.30-0.93 vs. 3.70, 1.38-8.33, P < 0.001), although platelet counts were similar (mean 321 x 10(9)/l, range 42-1,040 vs. 253 x 10(9)/l, 124-381). Two patients died of hepatic failure. TPO levels were measured in five patients after regression of the blast cells. With regression of blast cells, TPO levels were remarkably increased in four survived patients. In one patient with hepatic failure, TPO level was poorly elevated and relatively lower compared to the others. TPO levels were inversely correlated with blast numbers (r = -0.85, P < 0.001), but not with platelet counts (r = 0.426). Blast cells from four patients were all positive for c-Mpl. Our findings suggest that megakaryocyte mass is a major regulator of TPO levels and hepatic failure may affect the TPO level because liver is a major source of TPO production.

Cell Count↗
PubMed1998

Eosinophil infiltration and degranulation in normal human tissue.

Localization of eosinophil granule major basic protein by immunofluorescence permits recognition of both eosinophil infiltration and degranulation. Over the past decade and a half, our laboratory has shown that eosinophil infiltration and degranulation occur in many diseased tissues in humans; among normal tissues studied as controls, only the gut showed striking eosinophil infiltration and degranulation. Using an indirect immunofluorescence procedure for the detection of major basic protein, we extended our analyses of normal human tissues to include tissues from essentially all body organs; a total of 117 biopsy/autopsy specimens were analyzed. To determine whether the method of tissue procurement affected the level of eosinophil degranulation in the normal gastrointestinal tract, normal proximal jejunum from six patients was biopsied using either an endoscopic forceps or a scalpel at the time of elective surgery and examined by immunofluorescence. Spleen, lymph node, and thymus tissues showed eosinophil infiltration with scant evidence of degranulation, but the only organ showing both eosinophil infiltration and remarkable degranulation was the gastrointestinal tract. Eosinophil degranulation was significantly increased in specimens obtained by endoscopic forceps compared to those obtained by scalpel (P = 0.021). These results indicate that tissue procurement methods affect the degree of eosinophil degranulation in the gut. Thus, among normal human body organs, both eosinophil infiltration and appreciable degranulation consistently occur only in the gut.

Adult↗
PubMed1997

Successful hematopoietic reconstitution by transplantation of umbilical cord blood cells in a transfusion-dependent child with Diamond-Blackfan anemia.

A 4-year-old boy with Diamond-Blackfan anemia and a history of multiple transfusions underwent umbilical cord blood transplantation from his HLA-identical female sibling born by vaginal delivery at 38 weeks. The patient was prepared with busulfan, cyclophosphamide and antilymphocyte globulin. Methotrexate and cyclosporin A were given for the prophylaxis of GVHD. Regimen-related toxicity was not observed and successful engraftment occurred, including the erythroid series. No evidence of acute or chronic GVHD has been observed for 14 months after transplantation. This is the first case of successful umbilical cord blood transplantation to a patient with Diamond-Blackfan anemia.

Blood Transfusion↗
PubMed1996

Mite-specific induction of interleukin-2 receptor on T lymphocytes from children with mite-sensitive asthma: modified immune response with immunotherapy.

BACKGROUND: The efficacy of immunotherapy is still controversial. To elucidate the mechanisms of immunotherapy, we studied mite-specific induction of IL-2 receptor (IL-2R) expression on T lymphocytes from children with mite-sensitive asthma. METHODS: Peripheral blood mononuclear cells were obtained from 28 children with mite-sensitive asthma: 13 had never received house dust immunotherapy (nonimmunotherapy group), 15 had been receiving house dust immunotherapy at the time of the study (immunotherapy group). After a 6-day culture with or without Dermatophagoides farinae (Df) antigen, the expression of IL-2Rp55 (CD25) and p75 on CD4+ or CD8+ T lymphocytes was measured by flow cytometry. RESULTS: The nonimmunotherapy group showed significant Df-specific CD25 induction on CD4+ T lymphocytes (delta CD4+ CD25+) but little induction on CD8+ T lymphocytes (delta CD8+ CD25+). delta CD4+ CD25+ was correlated with the severity of the disease. In the immunotherapy group delta CD8+ CD25+ was significantly higher than in the nonimmunotherapy group or in normal subjects and correlated with Df-specific IgG4 and cumulative doses of house dust extract, whereas delta CD4+ CD25+ was similar in the nonimmunotherapy and the immunotherapy groups. IL-2Rp75 was not induced either on CD4+ or CD8+ T lymphocytes. CONCLUSIONS: Our data suggest that house dust immunotherapy may have induced Df-specific CD8+ T lymphocytes in patients with mite-sensitive asthma and that the efficacy of immunotherapy may be attributed to the generation of Df-specific CD8+ T lymphocytes.

Adolescent↗
PubMed1994

Pregnancy-associated major basic protein: deposition of protein and expression of mRNA at the maternal-fetal junction in early and late gestation.

Pregnancy-associated major basic protein (pMBP) has previously been isolated from human placenta and localized to the X cell. Here we used immunofluorescence staining and in situ hybridization to determine the distribution of pMBP and pMBP mRNA throughout the maternal-fetal junction in both early gestation tissues and at term. In early gestation tissues, pMBP was present only at the placental insertion site. Specifically, pMBP was present in (a) the decidua basalis (in the extracellular space, in interstitial pools and inside endometrial glands) and (b) intracellularly within extravillous interstitial trophoblasts in the decidua, in the myometrium and surrounding but not within luminal cells of spiral arteries. At term, the placental bed showed intense extracellular pMBP staining with little intracellular pMBP. In situ hybridization showed the presence of pMBP mRNA in both the early and late gestational tissues. pMBP mRNA was present in cells in the decidua, at the decidual-myometrial junction and in cell islands. Quantitative image analysis showed statistically significant hybridization signals with the pMBP antisense probe as compared to the control/sense probe. These results indicate that pMBP mRNA is expressed and pMBP is extensively deposited at the maternal-fetal junction in early pregnancy and at term.

Adult↗
PubMed1994

Localization of pregnancy-associated plasma protein-A and colocalization of pregnancy-associated plasma protein-A messenger ribonucleic acid and eosinophil granule major basic protein messenger ribonucleic acid in placenta.

BACKGROUND: The human eosinophil granule major basic protein (MBP), a 13.8 kilodalton cationic polypeptide constituting the core of the eosinophil granule, is cytotoxic to parasites and numerous mammalian cells. Concentrations of a molecule immunochemically similar to eosinophil granule MBP are present in maternal plasma, and MBP mRNA has been localized to placental X cells by in situ hybridization. Eosinophil granule MBP is initially translated as a nontoxic precursor (proMBP), containing a 9.9 kilodalton acidic pro-portion that is believed to neutralize MBP toxicity. Recent analyses of sera from pregnant women have revealed that pregnancy-associated plasma protein-A (PAPP-A), previously thought to be a homotetramer of PAPP-A subunits, is actually composed of PAPP-A subunits bound by disulfide bonds to equimolar amounts of proMBP molecules to form a complex, PAPP-A/proMBP. In addition, the PAPP-A subunit nucleotide and deduced amino acid sequence have been determined from cloned cDNA. The PAPP-A monomer found in plasma contains 1547 amino acid residues. EXPERIMENTAL DESIGN: Because of the new evidence that PAPP-A is complexed with proMBP, previous studies on the localization of PAPP-A using antibodies to PAPP-A must be questioned. To determine the localization of the PAPP-A subunit, immunofluorescence was performed on normal placental tissues using proMBP absorbed anti-PAPP-A antibody. Furthermore, the expression of PAPP-A mRNA was investigated by in situ hybridization. RESULTS: Immunofluorescence staining with proMBP absorbed anti-PAPP-A antibody showed that PAPP-A is localized to placental septa, anchoring villi, and the syncytia of chorionic villi, whereas MBP is localized only to septa and anchoring villi. By in situ hybridization, PAPP-A mRNA is detected in placental X cells and syncytiotrophoblasts, but MBP mRNA is localized only to placental X cells. CONCLUSIONS: The presence of PAPP-A mRNA and PAPP-A subunit protein in placental X cells and syncytiotrophoblasts indicates that both X cells and syncytiotrophoblasts synthesize the PAPP-A subunit, whereas only X cells synthesize proMBP.

Blood Proteins↗
PubMed1994

Expression of eosinophil-granule major basic protein messenger ribonucleic acid in placental X cells.

BACKGROUND: The human eosinophil-granule major basic protein (MBP) is a 13.8-kilodalton cationic polypeptide constituting the core of the eosinophil granule. MBP is cytotoxic to parasites and numerous mammalian cells and is a potent secretagogue for platelets, basophils, mast cells, and neutrophils. Concentrations of a molecule immunochemically similar to eosinophil granule MBP are present in maternal plasma, and MBP has been localized by immunofluorescence to placental X cells. EXPERIMENTAL DESIGN: To determine whether X cells produce MBP, the expression of MBP messenger RNA (mRNA) was investigated in placentas by Northern blot analyses and by in situ hybridization with 35S-labeled RNA probes. RESULTS: Northern blot analyses of RNA from placental septa and villi showed the existence of a 1.0-kb RNA band that hybridized with the MBP anti-sense probe; no MBP mRNA was detected in whole blood of normal or pregnant women or in cord blood. Analyses of placentas by in situ hybridization showed MBP mRNA in X cells of placental septa and anchoring villi, but not in other cellular elements such as syncytiotrophoblasts, cytotrophoblasts, villous stromal cells, and fetal endothelial cells. RNase pretreatment abolished X-cell hybridization signals; treatment of sections with an excess of nonradiolabeled anti-sense RNA also blocked binding of the 35S-labeled anti-sense RNA probe. Additional evidence supporting the production of MBP by X cells was obtained using a combination of in situ hybridization and immunofluorescence, which showed colocalization of MBP and its mRNA. CONCLUSIONS: The presence of MBP mRNA and MBP protein in placental X cells indicates that X cells synthesize this biologically active molecule.

Blood Proteins↗