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Biomedical subjects

S McKenzie

Publications and source records attributed to S McKenzie.

At least 19 recordsLinked to original sources
PubMed1992

Blastomycosis in patients with the acquired immunodeficiency syndrome.

OBJECTIVE: To describe the clinical, demographic, radiographic, diagnostic, and therapeutic aspects of blastomycosis in patients with the acquired immunodeficiency syndrome (AIDS). DESIGN: A retrospective survey. SETTING: Ten university medical centers and community hospitals, six in geographic areas endemic for Blastomyces dermatitidis, and four outside the endemic area. PATIENTS: We identified 15 patients with blastomycosis and positive serologic test results for human immunodeficiency virus (HIV). MEASUREMENTS: A diagnosis of blastomycosis was based on a positive culture (14 patients) or typical histopathologic features (one patient) for B. dermatitidis in clinical specimens. RESULTS: Twelve of 15 patients had a previous or concomitant AIDS-defining illness at the time of diagnosis of blastomycosis, and only one patient had a CD4 lymphocyte count of greater than 200 cells/mm3. Two patterns of disease emerged: localized pulmonary involvement (seven patients), and disseminated or extrapulmonary blastomycosis (eight patients). Central nervous system involvement was common (40%). Six patients died within 21 days of presentation with blastomycosis, including four patients with disseminated and two with fulminant pulmonary disease. Among the nine patients who survived longer than 1 month, all received amphotericin B as initial antifungal therapy, and most received subsequent therapy with ketoconazole. Only two of these nine patients died with evidence of progressive blastomycosis. CONCLUSIONS: Blastomycosis is a late and frequently fatal infectious complication in a few patients with AIDS. In these patients, overwhelming disseminated disease including involvement of the central nervous system is common, and it is associated with a high early mortality. Initial therapy with amphotericin B is appropriate in patients with AIDS and presumptive blastomycosis.

Acquired Immunodeficiency Syndrome↗
PubMed1992

Phorbol ester-induced hairy cell features on chronic lymphocytic leukemia cells in vitro.

Leukemic cells from eight patients with chronic lymphocytic leukemia were isolated and cultured in the continuous presence of 12-O-tetradecanoylphorbol 13-acetate (TPA) at a concentration of 1.6 x 10(-9) M for 4-10 days. Aliquots of cells were then analyzed at intervals of 24-72 hr for changes in morphology, acid phosphatase staining (AP), and expression of two hairy cell-associated surface antigens, HCL1 (CD22, Leu 14) and HCL3 (CD11c, Leu M5). All cases studied showed typical B-CLL phenotype, and only a small proportion of cells expressed CD22 and CD11c (mean 7% and 4.9%, respectively). TPA treatment induced the coexpression of CD22 (mean 49%) and CD11c (mean 48%) and tartrate-resistant acid phosphatase in seven of eight cases. Morphologically, cells in TPA cultures expressed hairy cell features that were evident in light and electron microscopic studies. Collectively these changes indicate that TPA can induce hairy cell features on CLL cells in vitro, suggesting the later maturational stage of HCL compared with CLL.

Acid Phosphatase↗
PubMed1991

Requirements for the internalization of a murine monoclonal antibody directed against the HER-2/neu gene product c-erbB-2.

A murine monoclonal antibody, TA1, is directed against an epitope on the extracellular domain of the HER-2/neu (c-erbB-2) gene product. Requirements for TA1-induced internalization of c-erbB-2 have been studied using the SKBr3 human breast cancer cell line and several rat fibroblast cell lines that express either wild-type or mutant human c-erbB-2. Internalization of TA1 was monitored by assaying protease-resistant uptake of 125I-labeled TA1, by electron microscopy of gold-labeled TA1, and by inhibition of clonogenic growth of cells incubated with TA1 that had been conjugated with blocked ricin. Similar rates of internalization of TA1 were observed in SKBr3 and in rat fibroblasts that expressed human c-erbB-2. The route of endocytosis was the same as that observed with antibodies against other membrane receptors. Anti-c-erbB-2 and anti-transferrin receptor cointernalized through clathrin-coated pits, coated vesicles, endosomes, and multivesicular bodies. Products of mutant c-erbB-2 that lacked a portion of the tyrosine kinase domain or that lacked most of the cytoplasmic domain were endocytosed in the presence of TA1 as promptly as the wild-type c-erbB-2 product. Slightly more rapid internalization of TA1 was observed in rat cells that expressed c-erbB-2 with a single point mutation in the transmembrane domain. Taken together, our data suggest that neither the intracytoplasmic domain nor receptor phosphorylation is required for antibody-mediated endocytosis of c-erbB-2.

Animals↗
PubMed1991

Results of a randomized trial comparing idarubicin and cytosine arabinoside with daunorubicin and cytosine arabinoside in adult patients with newly diagnosed acute myelogenous leukemia.

4'-Demethoxydaunorubicin (idarubicin [IDR]) is a new anthracycline that differs from its parent compound by the deletion of a methoxy group at position 4 of the chromophore ring. This minor structural modification results in a more lipophilic compound with a unique metabolite that has a prolonged plasma half-life as well as in vitro and in vivo antileukemia activity. To determine its activity in acute myelogenous leukemia (AML), 130 consecutive adult patients between the ages of 16 and 60 with newly diagnosed disease were randomized in a single institution study to receive either IDR in combination with cytosine arabinoside (Ara-C) or standard therapy with daunorubicin (DNR) and Ara-C. The trial was analyzed using the O'Brien-Fleming multiple testing design that allowed for periodic inspection of the data at specific patient accession points. After accrual of 60 patients per arm, analysis showed that patients who received IDR/Ara-C had a superior response compared with those who received standard therapy: 48 of 60 patients (80%) achieved complete remission on the former arm compared with 35 of 60 patients on the latter (58%, P = .005). Logistic regression analysis of factors associated with complete response indicated that treatment with IDR/Ara-C offered a significant advantage to patients who presented with a high initial white blood cell count compared with treatment with DNR/Ara-C. The degree of marrow aplasia was approximately the same on each arm as was nonhematologic toxicity. Overall survival for patients on the IDR/Ara-C arm was 19.5 months compared with 13.5 months on the DNR/Ara-C arm (P = .025) at a median follow-up of 2.5 years. We conclude that IDR/Ara-C can effectively replace standard therapy with DNR/Ara-C in adult patients less than age 60 with newly diagnosed AML.

Adult↗
PubMed1991

Case report: fatal pulmonary toxoplasmosis following chemotherapy.

A 41-year-old woman with acute myelomonocytic leukemia in remission died of a rapidly progressive necrotizing pneumonia while in the recovery phase following consolidation chemotherapy. Autopsy revealed disseminated toxoplasmosis. Although this syndrome has been well described to present as a neurologic complication in certain immunocompromised patients, it is rare in acute leukemia, and non-neurologic presentations are even more unusual. This case emphasizes the need to be suspicious of toxoplasmosis in immunocompromised patients even in the absence of neurologic signs or symptoms.

Adult↗
PubMed1991

Troublesome crying in infants: effect of advice to reduce stimulation.

The observation that babies with troublesome crying improve quickly in hospital suggested that, if true, a common, quickly reversible, factor may operate. Histories from parents of such babies suggest that much work goes into trying to console them. It is hypothesised that this may lead to excessive stimulation and the improvement seen in hospital reflects a reduction in stimulation. Two studies were undertaken. (1) Carers were asked to agree to randomisation of their infants to hospital or home management. Those at home were advised to reduce stimulation. A 10 point questionnaire was used to describe distress in mothers of subjects and age matched controls. (2) A randomised controlled study compared advice to reduce stimulation with an empathic interview using a +5 to -5 scale to chart change. In the first study too few subjects agreed to randomisation and thus a rigorous study to validate the observation could not proceed. There was good evidence, however, that crying improved. Results from the home group justified the second study. The median distress score for subjects was 7/10 and for controls 3/10 (p less than 0.001). In the second study at seven days, 18/22 subjects given advice scored +2 or better on the change chart for crying, compared with 7/20 of those who did not receive advice (p less than 0.01). After the latter received advice 79% improved (95% confidence interval 61 to 97%). For babies under 12 weeks, the customary upper limit for a diagnosis of colic, 14/15 subjects advised improved compared with 6/12 who were not advised (p less than 0.02). These studies have shown that infants with troublesome crying admitted to hospital seem to improve quickly as do those whose carers are advised to reduce stimulation.

Crying↗
PubMed1990

Interstitial brachytherapy for malignant brain tumors: preliminary results.

The authors report their experience with interstitial brachytherapy in 46 patients with malignant brain tumors. Twenty-three patients received implants after external radiation for newly diagnosed malignant astrocytoma, as part of a randomized study (Group I). Eighteen patients received implants for recurrent malignant astrocytoma (Group II) and 3 for recurrent solitary cerebral metastasis from adenocarcinoma of the lung (Group III). Two additional patients received implants as part of their initial therapy for a radiation-induced malignant astrocytoma and a malignant fibrous histiocytoma. In all patients high-activity iodine-125 sources were implanted temporarily by a stereotactic technique. To date 50 patients have been entered in the randomized study with a maximum follow-up of 31 months. The small numbers and short follow-up preclude any conclusions regarding the efficacy of brachytherapy used as part of initial therapy. The median survival to date in the 23 patients in this group who received implants is 60 weeks. The median survival to date for the 18 patients who received implants for recurrent malignant astrocytoma is 44 weeks postimplant. Two of the three patients who received implants for recurrent solitary metastasis are alive at 41 and 49 weeks postimplant; a third died at 39 weeks postimplant. Significant complications attributable to interstitial brachytherapy have been observed in 10 of 46 patients (21.7%). A second operation for clinical and radiological deterioration was performed in 12 patients (26.1%) 8 to 105 weeks after brachytherapy. The authors conclude that interstitial brachytherapy is beneficial for selected patients with recurrent malignant astrocytoma and solitary recurrent metastasis.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1990

The Bain, ADE, and Enclosed Magill breathing systems. A comparative study during controlled ventilation.

The Enclosed Magill, Humphrey ADE and the Bain breathing systems are all used for controlled ventilation of the lungs. This study compares the three systems in vitro with a lung model and in clinical practice. No difference was observed, with ventilatory variables commonly used in clinical practice, between the Bain and the ADE, while significantly lower end-tidal carbon dioxide values were observed with the Enclosed Magill (about 7%). Lower fresh gas flows can be used under these circumstances to maintain normocapnia with the Enclosed Magill than either the Bain or the Humphrey ADE.

Adult↗
PubMed1990

Expression of Mycobacterium tuberculosis and Mycobacterium leprae proteins by vaccinia virus.

Eight Mycobacterium tuberculosis and M. leprae genes were inserted into the vaccinia virus genome by in vivo recombination. The resulting virus recombinants were shown to express five different M. tuberculosis proteins (71, 65, 35, 19, and 12 kDa) and three M. leprae proteins (65 and 18 kDa and a biotin-binding protein) by Western immunoblot analysis, radioimmunoprecipitation, or black-plaque assay. When injected into BALB/c mice, the recombinants expressing the M. tuberculosis 71-, 65-, or 35-kDa protein and the M. leprae 65-kDa protein or the biotin-binding protein elicited antibodies against the appropriate M. tuberculosis or M. leprae protein. These vaccinia virus recombinants are being tested for the ability to elicit immune protection against M. tuberculosis or M. leprae challenge in animal model systems. The recombinants are also useful in generating target cells for assays aimed at elucidating the cellular immune responses to mycobacterial proteins in leprosy and tuberculosis. Furthermore, the M. tuberculosis 65-kDa protein and four of the other mycobacterial proteins share homology with known eucaryotic and procaryotic stress proteins, some of which may play a role in autoimmunity.

Animals↗
PubMed1989

Detection of major histocompatibility complex class I-restricted, HIV-specific cytotoxic T lymphocytes in the blood of infected hemophiliacs.

Major histocompatibility (MHC)-restricted, human immunodeficiency virus type one (HIV-1)-specific, cytotoxic T lymphocytes (CTLs) were detected in the peripheral blood mononuclear cells (PBMCs) of HIV-1-infected individuals. Using a system of autologous B and T lymphoblastoid cell lines infected with recombinant vaccinia vectors (VVs) expressing HIV-1 gene products, we were able to detect HIV-1-specific cytolytic responses in the PBMCs of 88% of HIV-1-seropositive hemophiliac patients in the absence of in vitro stimulation. These cytolytic responses were directed against both HIV-1 envelope and gag gene products. The responses were resistant to natural killer (NK) cell depletion and were inhibited by monoclonal antibodies (MoAbs) to the T cell receptor, CD8 surface antigens, and MHC class I antigens, suggesting a classical MHC class I restricted, virus-specific CTL response.

Antibodies, Monoclonal↗
PubMed1989

Antigenic specificity of antibody-dependent cell-mediated cytotoxicity directed against human immunodeficiency virus in antibody-positive sera.

Antibody-dependent cell-mediated cytotoxicity (ADCC) specific for human immunodeficiency virus (HIV) has been described for HIV-infected individuals. To determine the antigenic specificity of this immune response and to define its relationship to the disease state, an ADCC assay was developed using Epstein-Barr virus-transformed lymphoblastoid cell line targets infected with vaccinia virus vectors expressing HIV proteins. The vaccinia virus vectors induced appropriate HIV proteins (envelope glycoproteins gp160, gp120, and gp41 or gag proteins p55, p40, p24, and p17) in infected lymphoblastoid cell lines as demonstrated by radioimmunoprecipitation and syncytia formation with c8166 cells. Killer cell-mediated, HIV-specific ADCC was found in sera from HIV-seropositive but not HIV-seronegative hemophiliacs. This HIV-specific response was directed against envelope glycoprotein but was completely absent against target cells expressing the HIV gag proteins. The ADCC directed against gp160 was present at serum dilutions up to 1/316,000. There was no correlation between serum ADCC titer and the stage of HIV-related illness as determined by T-helper-cell numbers. These experiments clearly implicated gp160 as the target antigen of HIV-specific ADCC activity following natural infection. Vaccines which stimulate antibodies directed against gp160, which are capable of mediating ADCC against infected cells, could be important for protection against infection by cell-associated virus.

Antibody-Dependent Cell Cytotoxicity↗
PubMed1989

Oligoclonal immunoglobulins in HIV infection.

We tested 150 patients infected with human immunodeficiency virus (HIV) for the presence of oligoclonal bands in serum, prompted by reports that these abnormal proteins may have prognostic significance. Sixty HIV-negative individuals from "at-risk" groups were tested along with 80 HIV-negative, healthy blood donors for the presence of these bands. All sera were tested by isoelectric focusing, because it is more sensitive for this purpose than more-conventional electrophoretic techniques. In the HIV-positive group, 61% of the sera had oligoclonal bands; in the HIV-negative "at-risk" group, 36% had bands. No bands were detectable in sera from the healthy blood-donor group. Some patients were also followed for differing periods throughout their infection, and changes in their oligoclonal banding patterns could not be correlated with disease progression. The fact that oligoclonal bands were found to be present without HIV infection in a substantial number of individuals from within the "at-risk" groups leads us to conclude that the presence of oligoclonal bands in HIV infection is of limited prognostic significance.

HIV Seropositivity↗
PubMed1989

Analysis of the individual and combined reactivities of monoclonal antibodies H25, H366, and MY9 with normal progenitor cells and blast cells from patients with acute myeloblastic leukemia.

Recently we reported that two monoclonal antibodies (MoAbs), H25 and H366, which react with human natural killer cells and monocytes, also react with normal in vitro colony-forming cells including granulocyte-monocyte colony-forming units (CFU-GM), erythroid burst-forming units (BFU-E), and erythroid colony-forming units and with leukemic blasts in preliminary testing of cells from patients with myeloid leukemias and T cell acute lymphocytic leukemia. In the present studies we examined the reactivities of MoAbs H25, H366, and MY9 (singly or combined) with the total leukemic cell population and the leukemic clonogenic cells (L-CFC) from 28 patients with acute myeloblastic leukemia. Using cytofluorography, we found the extent of expression of antigen H25 comparable to MY9 in the majority of patients, and both were more highly expressed than antigen H366. Incubation with H25 and H366 MoAbs simultaneously did not increase the number of positive cells over that seen when stained with H25 alone; however, the amount of antibody fluorescence intensity (FI) was increased. Leukemic cells simultaneously stained with MoAbs H25, H366, and MY9 displayed the highest number of positive cells and FI. Using magnetic beads coated with sheep anti-mouse IgG for depleting antibody-binding cells, greater than or equal to 90% of L-CFC were depleted by a combination of H25 and H366 MoAbs in 76% of AML cases tested as compared to 41% of the cases with MoAb MY9. Using a MoAb cocktail of H25, H366, and MY9, greater than or equal to 90% of L-CFC were depleted in 94% of cases tested, and greater than or equal to 99% of L-CFC were removed in 76% of the cases. Using the same depletion methods for normal bone marrow cells, a combination of anti-H25 and anti-H366 removed 90%, 98%, and 84% of CFU-GM, BFU-E, and multipotent colony-forming units (CFU-GEM), respectively, whereas the cocktail of H25, H366, and MY9 MoAbs removed 98%, 99.5%, and 97% of CFU-GM, BFU-E, and CFU-GEM, respectively. Incubation of H25 and H366-depleted bone marrow cells for 2 weeks in the presence of irradiated adherent cell layers from long-term marrow cultures generated CFU-GM and some BFU-E, as did H25, H366, and MY9-depleted marrow cells, although to a much lesser extent. Based on the overall data, combinations of H25, H366, and MY9 MoAbs and immunomagnetic beads conceivably might have therapeutic potential for ex vivo elimination of leukemic cells from AML remission marrows prior to autologous transplantation.

Adult↗
PubMed1989

Monoclonal antibody M195: a diagnostic marker for acute myelogenous leukemia.

Monoclonal antibody (mAb) M195 is a mouse IgG2a reactive with a myelomonocytic differentiation antigen found on early myeloid cells and monocytes. The reactivity of M195 with fresh hematopoietic neoplasms in the blood or bone marrow from 227 patients at Memorial Hospital was determined by flow cytometry. M195 was positive on 67% of 61 myeloblastic leukemias. Seventy percent of Tdt-negative ANLL and 30% of Tdt-positive ANLL were positive; 100% of CMMOL and 100% of CML in myeloblastic crisis or accelerated phase were positive. In contrast, M195 was positive on only 8% of 51 lymphoblastic leukemias and 1% of 70 other nonmyeloid samples. M195 binding did not correlate well with FAB classification of ANLL. The pattern of reactivity of M195 was similar but not identical to that of MY9 (CD33) on the same cases (83% concordance). Cross-blocking of M195 binding by MY9 and L4F3 (CD33) was demonstrated. M195 may bind to a different epitope on the same protein antigen. The presence of both MY9 and M195 positivity on a leukemia sample had a 98% specificity of diagnosing ANLL, which was greater than MY9 alone (88%) or M195 alone (92%). Assays of granulocytic-monocytic and erythroid colony-forming units showed M195 to be present on these hematopoietic progenitors. This pattern of reactivity of M195, together with its lack of reactivity with mature granulocytic elements or with adult tissues, make it a candidate for therapy of ANLL in vivo.

Animals↗