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Biomedical subjects

M C Poon

Publications and source records attributed to M C Poon.

At least 19 recordsLinked to original sources
PubMed1992

Allogeneic bone-marrow transplantation without protective isolation in adults with malignant disease.

Bone-marrow transplant (BMT) patients are severely immunocompromised immediately after the procedure and they are commonly nursed in strict protective isolation to reduce the risk of both infection and graft-versus-host disease (GvHD). We have studied a consecutive series of patients to see whether protective isolation is of benefit as prophylaxis against infectious complications of BMT. 50 consecutive patients who had malignant disease and received their first BMT from siblings or unrelated donors were nursed in standard single rooms with visitors instructed to wash their hands. A subset of 20 patients living locally spent a median of 25 days in hospital after BMT; they also spent some time at home on a median of 8 days before engraftment and 3 patients went home on more than 90% of their hospital days. 16 patients (32%) had positive bacterial cultures and/or focal infection. Gram-positive bacteraemia was found in 12 subjects (24%) but there were no gram-negative or deep fungal infections. Grade II or III acute GvHD developed in 17 patients (34%). There were no deaths from infection or acute GvHD. Transplant-related mortality was 6% in the first 100 days and 18% overall with a median follow-up of 22 months. Our mortality data compare favourably with those from institutions with strict isolation procedures. We conclude that BMT may be safely completed in some institutions without either protective isolation or the need to confine patients continuously in hospital.

Acute Disease↗
PubMed1992

Identification of factor IX mutations in haemophilia B: application of polymerase chain reaction and single strand conformation analysis.

The molecular characterization of two haemophilia B defects, Calgary 1 and Calgary 2, was carried out using polymerase chain reaction (PCR) amplification and direct dideoxy sequencing. It had been previously shown that the Calgary 1 mutation affects the 5' TaqI restriction site of exon VIII, whereas Calgary 2 involves the loss of the 3' TaqI site of exon VIII of the factor IX gene. Sequencing data has now revealed that each of these alterations involves a C-to-T transition within a CpG dinucleotide. In each instance an arginine residue is replaced by a stop codon. These cases represent the recurrence of each particular alteration, both of which are predicted to result in the production of a truncated protein lacking a significant part of the catalytic region. A recently developed technique that reveals base substitutions as single-strand conformation polymorphisms (SSCP) was adapted for modelling in the detection of point mutations. Referred to here as single-strand conformation (SSC) analysis, this procedure, used in association with PCR, provided a reliable and sensitive system for molecular diagnosis in each of the cases presented. Computer-generated secondary structure predictions demonstrated a strong correlation with experimental results and the technique was used to screen 11 additional patients in the same region. A change detected by SSC analysis in one patient was localized to 55 base pairs, sequenced, and identified as a conservative amino acid substitution. This patient is now referred to as Calgary 3.

Base Sequence↗
PubMed1992

Hemophilia A carrier detection by restriction fragment length polymorphism analysis and discriminant analysis based on ELISA of factor VIII and vWf.

We performed carrier determination on female subjects from 32 hemophilia A kindreds with a combination of restriction fragment length polymorphism analysis and discriminant analysis of factor VIII antigen and von Willebrand factor antigen analyzed by enzyme-linked immunosorbent assay. Subjects included 25 obligate carriers, 30 at-risk female subjects from 19 kindreds each with two or more male subjects, with hemophilia and 28 at-risk female subjects from 13 kindreds each with a single sporadic case. Deoxyribonucleic acid (DNA) analysis with factor VIII intragenic probes clarified the carrier status of 15 female subjects, and extragenic probes classified an additional 14. Discriminant analysis, which identified 24 of 25 (96%) obligate carriers with carrier probabilities greater than or equal to 0.71 and 37 of 39 (95.0%) normal female subjects with probabilities less than or equal to 0.30, was useful for clarifying the carrier status of the female subjects who were not helped by DNA analysis and those that were classified by extragenic probes alone. Twenty-nine female subjects could not be categorized by restriction fragment length polymorphism analysis because DNA was unavailable from the subject or from key family members, key female subjects were noninformative, or carriership could not be excluded by restriction fragment length polymorphism in kindreds with sporadic cases. We studied 28 of these female subjects by discriminant analysis; 15 had carrier probabilities of greater than or equal to 0.71, 12 less than or equal to 0.30, and 1 = 0.35. All carriers by extragenic probes had carrier probability values greater than or equal to 0.71, whereas all noncarriers had values less than or equal to 0.30. In some families, particularly those in which gonadal mosaicism was a possibility, extensive family studies together with DNA and discriminant analyses were required for clarifying the source of the mutation, and hence the carrier status of the at-risk female subjects. Thus DNA and discriminant analyses complement each other, and when combined with careful pedigree analysis, the power of carrier determination is increased in some families.

DNA↗
PubMed1991

Severe combined immune deficiency presenting with cyclic hematopoiesis.

At age 2 months a male infant presented with a cyclic clinical syndrome every 14-21 days that included pharyngeal aphthous ulcers, high fever, lymphadenopathy, pallor, and malaise. Serial blood studies indicated cycling of all blood cell elements, compatible with a diagnosis of cyclic hematopoiesis (CH). He also manifested a progressively severe immune deficiency, not described before in human CH. When first studied at age 5 months, he was hypogammaglobulinaemic with normal B lymphocyte numbers. By 6.5 months, he was agammaglobulinaemic. At age 8 months, he developed severe pneumocystis carinii pneumonia, and studies showed a state of severe combined immune deficiency. The patient received a bone marrow transplant from his HLA-identical sister with no preconditioning therapy. Subsequently, normal immune function developed and the cyclic hematopoiesis resolved. The majority of lymphocytes is of donor origin. Persistence of erythrocytes and neutrophils of recipient origin suggests that the hematopoietic stem cells were not abnormal. We speculate that this patient had a primary deficiency of a differentiation factor affecting maturation of lymphoid and myeloid progenitor cells.

Blood Cell Count↗
PubMed1991

Red blood cell alloimmunization complicating plasma transfusion.

Well-known adverse effects of plasma transfusion include viral transmission, allergic complications, and rare anaphylactic reactions. In making clinical decisions to transfuse plasma, a seldom-considered complication is that of red blood cell (RBC) alloimmunization. The authors report a patient in whom strong IgM and IgG anti-E and weak IgG anti-JKa RBC antibodies developed 15 days after infusion of two units of fresh-frozen plasma for volume expansion. These antibodies are potentially hemolytic. This case underscores the importance of considering risks of plasma infusion. Plasma should not be used casually, especially for indications for which alternate therapies, such as crystalloid and colloid solutions, are available.

Aged↗
PubMed1991

Morphologic, phenotypic, and cytotoxic analyses of C57BL/6 murine non-parenchymal liver cells: new evidence associating murine liver large granular lymphocytes with monocyte precursors and implications for tumor immunotherapy.

Non-parenchymal liver cells (NPCs) have been implicated in murine host resistance to hepatic metastases. We have examined the relative cell number, morphology, phenotype, and cytotoxic potential of Percoll fractionated C57BL/6 murine liver NPCs. Low density (Percoll fractions 2 and 3) cells showed a large granular lymphocyte morphology and made up 76% of all NPCs recoverable, while high density (fractions 5 and 6) showed a small lymphocyte morphology and made up 10% of all NPCs. Low density cells demonstrated the following phenotype: 14% of the cells demonstrated the Thy 1.2 marker; 12%, the Lyt-2 marker; 67%, the L3T4 marker; 74%, the asialo GM1 marker; 30%, the 49H.8 marker; and 65%, the F4/80 marker. The high density cells expressed the same markers on 71%, 21%, 33%, 68%, 37%, and 19% of their cell surface, respectively. There were no differences phenotypically between high density NPCs and splenocytes except for the F4/80 expression (fractions 5 and 6 NPCs, F4/80 expression 19%, fresh splenocytes 60%). Dual color analysis of L3T4+ NPCs documented that fractions 2 and 3 cells also expressed the F4/80 marker on 85% of their cell surface and the Thy 1.2 marker on 11% of their cell surface. The high density fractions 5 and 6 L3T4+ cells expressed the F4/80 marker on 16% of their cell surface, and the Thy 1.2 marker on 89% of their cell surface. Cytotoxicity against YAC-1 [a natural killer (NK) sensitive target], MCA-102 (a NK resistant target), and WEHI-164 (a natural cytotoxicity target) were similar for fractions 2 and 3, and 5 and 6 cells. Based upon the expression of the F4/80 marker on L3T4+ cells that are Thy 1.2 negative and appear to be similar to LGLs morphologically (fractions 2 and 3 NPCs), we propose that these cells are monocyte precursors while fractions 5 and 6 cells are small lymphocytes. These findings with liver LGLs support the need for the evaluation of monocyte directed biological response modifiers in therapeutic models of murine hepatic metastases.

Animals↗
PubMed1991

Detection of two abnormal hemoglobins, Hb Manitoba and Hb G-Coushatta, during analysis of glycohemoglobin (A1c) by high-performance liquid chromatography.

This report concerns the detection of two abnormal hemoglobins (Hb), Hb Manitoba and Hb G Coushatta, during analysis for glycohemoglobin (Hb A1c). Blood samples from two diabetic patients, analyzed for Hb A1c by HPLC, were found to contain additional Hb peaks. The presence of an abnormal Hb was confirmed in both instances by hemoglobinopathy studies. Structural studies determined the two Hb variants to be Hb Manitoba (alpha 2 102 Ser----Arg beta 2) and Hb G-Coushatta (alpha 2 beta 2 22 Glu----Ala). The significance of the presence of an abnormal Hb in Hb A1c analysis is discussed.

Amino Acid Sequence↗
PubMed1991

Hemorrhagic disorder due to an isoniazid-associated acquired factor XIII inhibitor in a patient with Waldenström's macroglobulinemia.

A case is described of a 75-year-old woman with a history of pulmonary tuberculosis and Waldenström's macroglobulinemia who developed an inhibitor of coagulation factor XIII while taking isoniazid. The patient presented with a subcutaneous hematoma of the abdominal wall that extended from the xiphoid process to the symphysis pubis and measured 20 cm in diameter. Results of routine coagulation studies were normal with the exception of an increased solubility of the patient's plasma clot in 5M urea consistent with a deficiency of factor XIII activity. Persistence of the deficiency following a 1:2 dilution of the patient's plasma in normal plasma indicated the presence of an inhibitor. A sample of the patient's plasma was depleted of IgG by streptococcal protein G adsorption. The IgG-depleted plasma did not inhibit factor XIII activity, indicating that the inhibitory activity was not attributable to the underlying IgM paraprotein. The patient's purified IgG, on the other hand, inhibited factor XIII activity and the inhibitory activity could be neutralized by anti-IgG antibody. The patient's IgG also inhibited factor XIII-mediated incorporation of fluorescent monodansylcadaverine into casein. Binding of the patient's IgG to factor XIII concentrate was demonstrated by enzyme-linked immunosorbent assay and the IgG that bound to the factor XIII was demonstrated to be polyclonal. Isoniazid was discontinued after the patient was admitted to the hospital. Cryoprecipitate infusion controlled bleeding and reduced the inhibitor titer by 50%. Treatment with cyclophosphamide and prednisone, followed by extracorporeal immunoadsorption over a staphylococcal protein A column, did not reduce the inhibitor titer further. Plasma exchange therapy reduced the inhibitor titer to undetectable levels but failed to restore factor XIII activity. Infusions of factor XIII concentrate reproducibly restored factor XIII activity and were not associated with an anamnestic rise in the inhibitor titer. This represents the seventh reported case of an acquired inhibitor to factor XIII associated with the ingestion of isoniazid.

Aged↗
PubMed1990

Analysis of liver lymphoid cell subsets pre- and post-in vivo administration of human recombinant interleukin 2 in a C57BL/6 murine system.

The systemic administration of high dose recombinant interleukin 2 (RIL-2) can mediate significant reductions in the number of hepatic metastases in a murine system. This effect is sensitive to host irradiation. Both large granular (LGLs) and small (SLs) lymphocytes have been implicated as the cells mediating the antitumor effect. Utilizing selective Percoll fractionation of liver nonparenchymal lymphoid cells, we have attempted to determine the cell types involved in tumor immunotherapy of murine liver metastases during RIL-2 administration. At a RIL-2 dose of 25,000 units given i.p. three times a day, the total number of lymphoid cells seen in murine livers reached a peak on day 6 after the onset of RIL-2 therapy, lasting until day 10 and ranging from 25 to 29 times baseline values. Both LGLs and SLs were identified and SLs made up over one-half the cells present in murine livers. Phenotypic analysis of LGLs and SLs revealed that during exposure to RIL-2, bands 5 + 6 SLs expressed the Thy-1.2, Lyt-2, and Lyt-1 antigens to a greater degree than LGLs. LGLs exposed to RIL-2 demonstrated a decrease in the expression of the asialo GM1 antigen during exposure to RIL-2; however, the 49H.8 antigen normally expressed on natural killer cells and not on circulating T-cells was found only on LGLs. The role of murine liver LGLs and SLs needs to be further characterized.

Animals↗
PubMed1990

Treatment of an aggressive non-Hodgkin's lymphoma during pregnancy with MACOP-B chemotherapy.

Non-Hodgkin's lymphoma occurring during pregnancy is a rare event. A young woman at 18 weeks gestation with twins presented with a B-cell immunoblastic lymphoma. Combination chemotherapy with methotrexate, doxorubicin, cyclophosphamide, vincristine, prednisone, and bleomycin (MACOP-B) was instituted after limited staging. There was excellent response and the 12 weekly chemotherapy protocol was completed in 13 weeks. Twin male infants were born at 28 weeks gestation by cesarean section for premature labor. There was no evidence of any congenital malformations or hematologic suppressions. We believe this to be the first report of aggressive weekly chemotherapy during pregnancy; this approach to treatment in aggressive non-Hodgkin's lymphoma is both efficacious and safe.

Adult↗
PubMed1986

T lymphocytes from hemophiliacs proliferate after exposure to factor VIII product.

Chronic exposure of hemophiliacs to allogeneic proteins via factor VIII concentrate for control of bleeding could lead to a state of chronic antigen stimulation. Immune function from eight hemophiliacs requiring large amounts of factor VIII concentrate was assessed. It was found that 5 of 8 had a positive blastogenic response to low concentrations of factor VIII in a 7-day thymidine uptake assay. Separation of lymphocyte subpopulations indicated that the reactivity was contained in the T cell-enriched fraction. There was no blast transformation noted secondary to the factor VIII product in 20 controls tested in a 7-day assay nor was there any mitogenic effect of the factor VIII in a 3-day assay. In fact, high concentrations of factor VIII impaired that T lymphocytes from hemophiliacs are antigenically primed to some constituent in the lyophilized factor VIII concentrate.

Adult↗
PubMed1986

Natural killer cell activity from hemophiliacs exhibits differential responses to various forms of interferon.

Patients with hemophilia are at risk for the development of acquired immunodeficiency syndrome (AIDS). Patients with AIDS have recurrent infections and/or malignancy and altered immune response, including decreased T lymphocyte counts, decreased T helper lymphocytes, defective T cell blastogenesis, hypergammaglobulinemia, defective natural killer (NK) activity and impaired response of NK to interferon-beta (IFN-beta). It is feasible that chronic antigen stimulation with subsequent release of interferon could be related to the impaired NK reactivity to IFN-beta of patients with AIDS. Because hemophiliacs are subjected to chronic antigen stimulation secondary to the administration of foreign protein, the reactivity of NK cells from patients with hemophilia to IFN-alpha, IFN-beta and IFN-gamma was studied. Eight patients with hemophilia requiring high levels of clotting factor replacement were assessed. Three patients were antibody positive to HTLV-III. All had normal baseline NK cell function. In the first set of experiments, all patients responded normally to in vitro IFN-alpha by increasing NK activity, but four patients had significant failure and two had mild impairment in NK response to IFN-beta. This latter observation was particularly evident at very low concentrations of IFN. In repeated experiments, seven of eight had impaired NK response to IFN-beta and IFN-gamma but normal response to IFN-alpha. Only one patient's NK cells responded better to IFN-gamma. There was no obvious correlation of these findings to antibody status to HTLV-III. Chronic antigen stimulation and the modulation of interferon receptors are discussed as possible mechanisms that could produce these findings.

Adult↗
PubMed1979

Multiple myeloma masquerading as chromophobe adenoma.

A 62-year-old woman presenting with intracranial lesion eroding the sella with compression of optic chiasma was found to have plasmacytoma of the pituitary area. At the time of initial surgery, the patient had no biochemical, immunologic or marrow findings of multiple myeloma. The intracranial tumor was interpreted initially as chromophobe adenoma on light microscopy, but the diagnosis of plasmacytoma was established by electron microscopic examination of the tumor. The case illustrates the usefulness of electron microscopy as a diagnostic tool.

Adenoma, Chromophobe↗