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Biomedical subjects

R Morgan

Publications and source records attributed to R Morgan.

At least 181 records · Page 10Linked to original sources
PubMed1992

Cytogenetic and FISH studies of abnormal X chromosomes in a patient with ANLL.

We report a case of idic(X)(q13),r(X)(p22q13), and del(X)(:p11-->cen-->q11:) in a 71-year-old female patient with de novo acute nonlymphocytic leukemia (ANLL), FAB-M4. The abnormal X chromosomes of this patient were identified cytogenetically by G-banding technique and were further confirmed by fluorescence in situ hybridization (FISH) using an alpha-satellite probe to chromosome X centromere. The features of this are compared with other cases reported in the literature.

Aged↗
PubMed1992

Critical loads and steady-state chemistry for streams in the state of Maryland.

The critical loads to streams, steady-state stream chemistry and catchment chemical weathering rate in 73 catchments has been determined in the state of Maryland, USA. It was calculated with the PROFILE model from chemical limits for biological indicators, soil mineralogy, soil texture, annual average temperature, average soil moisture, net long-term uptake of base cations and nitrogen to the vegetation, annual precipitation and runoff and deposition of sulphur and nitrogen precursors of acid deposition. The results show a full range of critical loads from very low values in the sensitive catchments of western Maryland and the Coastal Plain on the Chesapeake Bay, to insensitive catchments in the Fredrick Valley and Ridge and the Piedmont plain. The critical loads will be used as an input to an integrated regional assessment of the quantitative sensitivity of streams to acid rain, and the assessment of regional stream alkalinity response to different abatement strategies. The mapping of steady-state stream chemistry indicates that streams in Maryland are still acidfying under the present deposition load. Land-use seems to play an important role in maintaining neutral pH in many of the streams of Maryland.

Journal Article↗
PubMed1992

Cell-mediated cytolysis of lymphoblastoid cells expressing Marek's disease virus-specific phosphorylated polypeptides.

Cell-mediated immune responses against Marek's disease virus (MDV)-antigens were examined using reticuloendotheliosis virus (REV)-transformed lymphoblastoid cell line CU91 and three cell lines derived from CU91. CU210 was established by establishing a latent MDV infection in CU91. Transfection of CU210 with pNL1, a selectable plasmid or with pNL1 and the cloned BamHI A fragment of MDV DNA resulted in the establishment of CU212 and CU211, respectively. CU211 expressed a MDV-specific phosphorylated polypeptide, while CU210 and CU212 were negative for MDV antigens. Only CU211 was lysed by MDV-specific effector cells. All cell lines were lysed by syngeneic REV-specific effector cells, although high levels of expression of the phosphorylated protein reduced the level of REV-specific lysis.

Animals↗
PubMed1992

Nonorthopedic use of the fracture table.

Use of the fracture table for patient positioning instead of the standard operating room table is advantageous in many nonorthopedic surgical situations. Benefits include circumferential accessibility of bilateral lower extremities, permitting two or more surgical teams to work simultaneously on different anatomical sites. Burns and multiple acute and chronic leg wounds are particularly suitable for this technique.

Adult↗
PubMed1992

Specific nutrient abnormalities in asymptomatic HIV-1 infection.

OBJECTIVE: To determine whether specific nutrient abnormalities occur in earlier stages of HIV-1 infection, thereby preceding the marked wasting and malnutrition that accompany later stages of the infection. DESIGN: A longitudinal investigation to determine biological, psychological and social factors thought to influence the progression and outcome of HIV-1 infection. Nutritional status was assessed using biochemical measurement of nutrient levels, dietary history, anthropometry and clinical examination for the signs and symptoms of nutritional deficiency or excess. SETTING: The study was performed on an outpatient basis at the University of Miami School of Medicine. PARTICIPANTS: One hundred homosexual men, aged between 20 and 55 years, who were asymptomatic other than persistent generalized lymphadenopathy (Centers for Disease Control stage III) and 42 age-matched homosexual men demonstrated to be free of HIV-1 infection at two 6-month intervals. MAIN OUTCOME MEASURES: Biochemical measurement of nutrient status, dietary history, anthropometry, clinical signs or symptoms of nutritional excess or deficiency were obtained for all participants. RESULTS: Despite few differences in mean blood levels of specific nutrients, prevalence of specific nutrient abnormalities was widespread among HIV-1-infected subjects, compared with non-infected male homosexual controls. Overtly and marginally low blood levels of vitamins A (18%), E (27%), riboflavin (26%), B6 (53%), and B12 (23%), together with copper (74%) and zinc (50%) were documented in HIV-1-seropositive subjects. With the exception of riboflavin, zinc, and copper, a similar prevalence of abnormalities among HIV-1-seronegative controls was not observed. CONCLUSION: Specific nutrient abnormalities occur with relative frequency in asymptomatic HIV-1 infection and may contribute to the rate and form of HIV-1 disease progression.

Adult↗
PubMed1992

Cognition and immune function in HIV-1 infection.

OBJECTIVES: To determine (1) whether there were differences in cognition between HIV-1-seropositive and HIV-1-seronegative homosexual men and (2), if so, whether these differences could be explained by the degree of immunosuppression [i.e., CD4 cell count and immunoglobulin A (IgA) levels]. DESIGN: A cross-sectional design was used to compare 66 HIV-1-seropositives (Centers for Disease Control stages II and III, n = 56; stages IVA and IVC-2, n = 10) and 37 HIV-1-seronegatives. The HIV-1-seropositives were classified into three immune groups based on their CD4 cell count (x 10(6)/l) and serum IgA level (mg/dl): (1) moderate [(n = 35) CD4 greater than 400, IgA less than 300]; (2) mixed [(n = 22) either CD4 greater than 400 and IgA greater than 300 or CD4 less than 400 and IgA less than 300] and (3) poor [(n = 9) CD4 less than 400, IgA greater than 300]. HIV-1-seronegatives formed the 'good' immune group (CD4 greater than 400 and IgA less than 300). METHODS: The four groups were compared on tests of verbal and visual memory, information-processing speeds, visuospatial skills, language processes, attention, psychomotor reaction time, and mental status. Factors other than HIV-1 sero-status that can influence cognitive performance were tested as covariates. RESULTS: HIV-1-seropositives had slower information-processing speeds and decreased verbal and visual memory, compared with HIV-1-seronegatives. These differences in cognition were not due to differential immunosuppression or to clinical status among the HIV-1-seropositives. CONCLUSIONS: Cognitive alterations occur in HIV-1-infected individuals before AIDS and appear to be independent of clinical status and degree of immunosuppression as measured by CD4 cell count and IgA levels.

Adult↗
PubMed1992

Effects of the human immunodeficiency virus type 1 Tat protein on the expression of inflammatory cytokines.

Increased levels of inflammatory cytokines, including tumor necrosis factor (TNF), interleukin-1 (IL-1), and IL-6, have been detected in specimens from human immunodeficiency virus type 1 (HIV-1)-infected individuals. Here we demonstrate that HIV-1 activates the expression of TNF but not of IL-1 and IL-6 in acutely and chronically infected T cells. The increase in TNF gene expression is due to activation of the TNF promoter by the viral gene product Tat. Transactivation of TNF gene expression requires the product of the first exon of the tat gene and is cell type independent. T cells chronically infected with pol-defective HIV-1 provirus constitutively express both Tat and TNF at levels significantly higher (fivefold) than those seen in control cells, and treatment with phorbol myristate acetate greatly enhances Tat expression and TNF production. As TNF can increase the production of IL-1 and IL-6 and these inflammatory cytokines all enhance HIV-1 gene expression and affect the immune, vascular, and central nervous systems, the activation of TNF by Tat may be part of a complex pathway in which HIV-1 uses viral products and host factors to increase its own expression and infectivity and to induce disease.

Animals↗
PubMed1991

Reversal of multidrug resistance in HL-60 cells by verapamil and liposome-encapsulated doxorubicin.

The means of circumventing multidrug resistance was investigated in HL-60 and HL-60R (a drug resistance variant) cell lines. The HL-60R cell line was developed from the parent line by serial exposure to increasing concentrations of doxorubicin over a 4-month period. This drug resistant cell line expressed P-glycoprotein in its cell surface and is 80-fold more resistant than the parent cell line. Multidrug resistance, as evaluated by a cell cytotoxicity assay using doxorubicin, can be overcome by use of verapamil. Multidrug resistance can also be circumvented when doxorubicin is encapsulated in liposomes. The combination of verapamil and doxorubicin-encapsulated liposomes does enhance circumvention of multidrug resistance beyond the effect of each agent alone, implying a synergistic effect. The lipid composition of the liposomes does affect the rate of drug uptake but not the overall cytotoxic effect of doxorubicin. The synergistic reversal of multidrug resistance by doxorubicin-encapsulated liposomes and verapamil suggests a multifactorial basis for drug resistance in this cell line.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1991

Lymphocytes as cellular vehicles for gene therapy in mouse and man.

The application of bone marrow gene therapy has been stalled by the inability to achieve stable high-level gene transfer and expression in the totipotent stem cells. We show that retroviral vectors can stably introduce genes into antigen-specific murine and human T lymphocytes in culture. Murine helper T cells were transduced with the retroviral vector SAX to express both neomycin-resistance and human adenosine deaminase genes. These cells were expanded in culture and selected for expression of neomycin resistance with G418. The gene insertion, selection, and culture expansion did not alter antigen specificity or growth characteristics of the T cells in vitro. To determine if cultured T cells might be used for gene therapy, their persistence and continued expression of the introduced genes was evaluated in nude mice transplanted with the SAX-transduced T cells. G418-resistant cells could be readily recovered from the spleens of recipients of transduced T cells for several months. In addition, recovered cells continued to produce human adenosine deaminase. Based on these observations, we studied cultured human tumor-infiltrating lymphocytes as a candidate cell for a trial of gene transfer in man. Exponential cultures of interleukin-2-stimulated tumor-infiltrating lymphocytes were efficiently transduced with the neomycin-resistance gene using the retroviral vector N2. Gene insertion and subsequent G418 selection did not substantially alter the growth characteristics, interleukin 2 dependence, membrane phenotype, or cytotoxicity profile of the transduced T cells. These studies provided a portion of the experimental evidence supporting the feasibility of the presently ongoing clinical trials of lymphocyte gene therapy in cancer as well as in patients with adenosine deaminase deficiency.

Animals↗
PubMed1991

Phase II study of 4'-deoxydoxorubicin (esorubicin) in advanced or metastatic adenocarcinoma of the stomach.

4'-deoxydoxorubicin (DxDx) was administered to 17 patients with locally advanced or metastatic gastric adenocarcinoma. Treatment cycles were repeated every 21 days. 15 eligible patients with a Karnofsky performance status of 50% or better (median: 70%) received at least one course of treatment; a median of 2 courses of DxDx was delivered (range 1 to 13). The median dose per treatment course was 26 mg/m2 (range 8.5 mg/m2 to 53 mg/m2). 69% of patients required dose reduction following the first course of therapy due to grade 3 or 4 myelosuppression, primarily neutropenia. The principal side effects included anemia, mild gastrointestinal toxicities, and alopecia; one patient experienced a 10% decrease in cardiac ejection fraction without clinical cardiac toxicity. Of the 15 patients assessable for response and toxicities, 1 patient had a partial response lasting 2.5 months. The median survival from the time of the first treatment was 3.3 months. We conclude that DxDx has only limited activity in the treatment of advanced gastric adenocarcinoma.

Adenocarcinoma↗
PubMed1991

Cytogenetic findings in typical and atypical meningioma.

Comparative pathological and karyotypic findings of a typical and an atypical meningioma in two different patients are presented. The chromosomal abnormalities observed appeared unique for the histopathological subtype of the tumor. Cytogenetic analysis of atypical meningioma has not previously been reported.

Adult↗
PubMed1991

t(16;21)(p11.2;q22): a recurrent primary rearrangement in ANLL.

We have identified three patients with acute nonlymphocytic leukemia (ANLL), subtypes M2, M4, and M7, who had a t(16;21)(p11.2;q22) in the affected cells. There are six previously reported cases of ANLL with the same t(16;21). The t(6;21) should therefore be included as another primary rearrangement in ANLL. Follow-up of these cases, though still limited, suggests a poor prognosis, as most patients have achieved a clinical remission but only for a short duration.

Adult↗
PubMed1991

Translocation (3;21) characterizes crises in myeloid stem cell disorders.

Three patients, one with Philadelphia (Ph) chromosome positive chronic myelocytic leukemia (CML) and two with primary acquired myelodysplastic syndromes (MDS), have been identified to have a t(3;21)(q26;q22). In the patient with CML, the t(3;21) was detected only in the blast phase. The t(3;21) as the sole abnormality appeared at presentation of MDS [refractory anemia with excess blasts (RAEB)] in one patient and remained as such when progression to RAEB in transformation (RAEB-t) occurred. The other patient with MDS had the t(3;21), in addition to other changes, during the progression of the disease. Thus, t(3;21) may characterize myeloid crises of clonal hematopoietic stem cell disorders (HSCD) and indicates a poor prognosis. As a primary cytogenetic event it may be also involved in the genesis of myelodysplasia with subsequent leukemic transformation.

Aged↗
PubMed1991

Nonradioactive in situ hybridization. A rapid approach for the identification of marker chromosomes: study of a case of acute leukemia with a Yq specific DNA probe.

Nonradioactive in situ hybridization provides a rapid method for detecting specific nucleic acid sequences. In this study of a patient with acute leukemia, we applied in situ hybridization for identification of a marker chromosome and determination of the number of copies of this marker in interphase nuclei using a biotinylated Yq-specific DNA probe (pY3.4). We show that nonradioactive interphase in situ hybridization can be a useful method for karyotypic analysis in addition to routine cytogenetic techniques in neoplastic disorders.

Acute Disease↗
PubMed1991

Expression of the multidrug resistance gene product (P-glycoprotein) in myelodysplasia is associated with a stem cell phenotype.

Previous studies have indicated relative resistance to chemotherapy in the myelodysplastic syndromes (MDS) and associated acute leukaemia. To determine if multidrug resistance may contribute to chemoresistance in these disorders, we studied bone marrow specimens for P-glycoprotein expression (P-GP) by immunocytochemical staining with monoclonal antibodies reactive with cytoplasmic (C219) or surface epitopes (MRK16) of P-GP. Forty-five case specimens from 43 patients were studied, including 32 cases of primary MDS, seven cases of acute myeloid leukaemia (AML) following MDS, and six therapy-related haematological disorders. Cytogenetic analysis was available on 36 specimens. Two staining patterns were detected: (1) cytoplasm and plasma membrane, and (2) staining restricted primarily to the nuclear-cytoplasmic junction. P-GP was detected in seven (22%) cases of primary MDS, four (57%) cases of AML evolving from MDS, and five (83%) cases of therapy-related haematological disorders. Expression of P-GP was restricted to blasts and leukaemic monocytes, and was otherwise absent from terminally differentiated blood cells. Analysis of the relation between P-GP expression and reactivity with the human progenitor cell antigen CD34, revealed a highly significant association (P = 0.001). P-GP reactivity was distributed equally among normal and abnormal karyotypes and did not correlate with specific cytogenetic abnormalities. These findings indicate that multidrug resistance in MDS and karyotypically-related haematological disorders is closely linked to a stem cell phenotype and may contribute to chemoresistance in these disorders.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1991

Molecular scanning of insulin-responsive glucose transporter (GLUT4) gene in NIDDM subjects.

We investigated the prevalence of mutations in the gene encoding the major insulin-responsive facilitative glucose transporter (GLUT4) in patients with non-insulin-dependent diabetes mellitus (NIDDM). All 11 exons of the GLUT4 gene from 30 British white subjects with NIDDM were amplified using the polymerase chain reaction and screened for nucleotide sequence variation using the single-stranded conformation polymorphism (SSCP) method. No variation between the study subjects was detected in exons 1-3, 4b-8, and 10. Variant SSCP patterns were detected in exons 4a and 9. SSCP variation in exon 4a was revealed by direct nucleotide sequencing to be due to a common silent polymorphism (AAC----AAT at Asn130). One NIDDM patient demonstrated a variant SSCP pattern in exon 9. This was caused by a point mutation (GTC----ATC) at codon 383, which leads to the conservative substitution of isoleucine for valine in the putative fifth extracellular loop of the transporter. Allele-specific oligonucleotide hybridization was used to examine the frequency of this mutation in 240 Welsh white subjects (160 with NIDDM and 80 controls). The Val----Ile383 mutation was found in the heterozygous state in two diabetic subjects and no control subjects. We conclude that mutations of the GLUT4 coding sequence are very uncommon in this population of subjects with typical NIDDM. Determining whether the Ile383 GLUT4 variant present in 3 diabetic subjects contributes in any way to their disease will require further study.

Alleles↗