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Biomedical subjects

R Morgan

Publications and source records attributed to R Morgan.

At least 199 records · Page 11Linked to original sources
PubMed1991

Association of vitamin B6 status with parameters of immune function in early HIV-1 infection.

Nutritional deficiencies have been documented to affect immune function. The present study indicates that vitamin B6 deficiency is prevalent in CDC stage III HIV-1-infected subjects, despite adequate dietary vitamin B6 intake. As vitamin B6 deficiency has been previously shown to affect immune function, these relatively asymptomatic HIV-1-infected patients were examined for evidence of a relationship between vitamin B6 deficiency and immune dysregulation. Vitamin B6 status in HIV-1-infected subjects was significantly associated with functional parameters of immunity [multivariate F(3,36) = 3.70, p less than or equal to 0.02]. Additional analyses indicated that overtly deficient participants exhibited significantly decreased lymphocyte responsiveness to the mitogens phytohemagglutinin and pokeweed, and reduced natural killer cell cytotoxicity, compared to subjects with clearly adequate vitamin B6 status (chi 2 = 8.78, df = 3, p less than 0.04). Vitamin B6 status was not related to immune cell subpopulations, e.g., CD4, CD8 cell number, or level of serum immunoglobulins. The results of this study indicate that while vitamin B6 status is not a primary etiological factor in HIV-1-related immunological dysregulation, it appears to be an important cofactor of immune function.

Acquired Immunodeficiency Syndrome↗
PubMed1991

Norepinephrine response in early HIV infection.

Norepinephrine response to a cold pressor test was investigated in 95 homosexual men in a longitudinal study of human immunodeficiency virus (HIV) infection. The baseline data obtained from 76 HIV+ and 19 HIV- subjects are included in this report. After the insertion of a venicatheter and following a 30 min rest, subjects immersed one of their hands in ice water for 2 min, and serial blood samples were obtained for the determination of catecholamine levels. The results show that the norepinephrine response in HIV+ subjects compared to that of HIV- subjects was blunted. Examination of the responses using linear and quadratic orthogonal polynomials suggested that these differences between the two groups were primarily a function of their rate of increase in norepinephrine levels. It was observed also that in HIV+ subjects, norepinephrine level peaked earlier than that in HIV- subjects. The data suggest that autonomic dysfunction is present in the early stages of HIV infection.

Autonomic Nervous System↗
PubMed1990

Structural alterations at the putative retinoblastoma locus in some human leukemias and preleukemia.

Homozygous loss of alleles of the retinoblastoma susceptibility locus (RB1) has been implicated in the onset of many different solid tumors. Heterozygous deletions of chromosome 13q14, the region containing the RB1 locus, have been observed by us in several subvariants of leukemia and preleukemia. We examined four cases of leukemia and one case of preleukemia for homozygous inactivation of the RB1 locus; in at least one case, evidence supports the concept that homozygous loss of both alleles of RB1 was an important step during leukemogenesis.

Adolescent↗
PubMed1990

Cognition in early human immunodeficiency virus infection.

Relatively little is known about cognitive changes in early human immunodeficiency virus (HIV) infection. This study examined cognitive functioning in 46 HIV-positive gay men relative to an age and education equivalent group of 13 HIV-negative gay men. The HIV-positive men were asymptomatic except for lymphadenopathy or T4 counts less than 700. The cognitive battery measured language, memory, visuospatial, information processing speeds, reasoning, attention, and psychomotor processes. The HIV-positive group was significantly slower in processing information and performed significantly less well than the HIV-negative group on certain verbal memory measures. Deviations of 1 as well as 2 SDs from the norm/control group mean on four or more tests were observed in 43% and 22% of the HIV-positive subjects, respectively, compared with 8% and none of the HIV-negative subjects, respectively. The results suggest that cognitive inefficiency occurs in a subsample of individuals during early HIV infection.

Adult↗
PubMed1990

Apparent duplication of inv(3)(q21q26) in one of five cases with inv (3) in myelodysplastic syndromes and acute leukemia.

Rearrangements affecting the long arm of chromosome 3 have been linked to abnormalities of platelet production and morphology in hematologic disorders. We present five patients with myelodysplastic syndromes or acute leukemia in whom inv(3)(q21q26) was seen. One of the patients showed an inversion of both homologs involving precisely the same breakpoints, suggesting apparent duplication of the abnormal chromosome 3 and loss of the normal homolog. To our knowledge this is the first report detailing such a condition.

Acute Disease↗
PubMed1990

Characterization of the breakpoint of a t(14;14)(q11.2;q32) from the leukemic cells of a patient with T-cell acute lymphoblastic leukemia.

The leukemic cells and derivative cell line from a 74-year-old male with T-cell acute lymphoblastic leukemia showed chromosomal abnormalities including a t(14;14)(q11.2;q32). This translocation is characteristic of a variety of T-cell malignancies, particularly T-cell prolymphocytic leukemia and the clonal proliferations of peripheral T cells in patients with ataxia-telangiectasia. Using DNA probes that spanned the T-cell receptor alpha chain (TCRA) joining (J) locus, the DNA rearrangement caused by the translocation was identified, cloned, and sequenced. The breakpoint shows site-specific juxtaposition of a TCRA joining segment and DNA from a region of 14q32 centromeric to the immunoglobulin heavy chain locus. Comparison of restriction map and nucleotide sequence from this translocation with other related chromosomal breakpoints suggests a dispersion of breakpoints throughout the 14q32 region.

Amino Acid Sequence↗
PubMed1990

The Apo(a) gene: structure/function relationships and the possible link with thrombotic atheromatous disease.

The last 25 years have witnessed an exponential increase of interest in the lipoprotein Lp(a). The structure of the gene encoding for its unique apo protein, Apo(a) has been determined resulting in possible structure/function relationships which may explain the close association between elevated levels of Lp(a) and atheromatous vascular disease. These findings may have profound therapeutic implications for the future treatment of the hyperlipidaemias and hypercholesterolaemia in particular.

Apolipoproteins A↗
PubMed1990

Immunologic abnormalities in chronic fatigue syndrome.

The chronic fatigue syndrome (CFS), formerly known as chronic Epstein-Barr virus syndrome, is a clinical state of some complexity and uncertain etiology. In order to characterize in a comprehensive manner the status of laboratory markers associated with cellular immune function in patients with this syndrome, 30 patients with clinically defined CFS were studied. All of the subjects were found to have multiple abnormalities in these markers. The most consistent immunological abnormality detected among these patients, when compared with normal controls, was low natural killer (NK) cell cytotoxicity. The number of NK cells, as defined by reactivity with monoclonal antibody NKH.1 (CD56), was elevated, but the killing of K562 tumor cells per CD56 cell was significantly diminished. Lymphoproliferative responses after stimulation with phytohemagglutinin and pokeweed mitogen were decreased in most patients when compared with those in normal controls, as was the production of gamma interferon following mitogen stimulation. Lymphocyte phenotypic marker analysis of peripheral blood lymphocytes showed that there were significant differences between patients with CFS and controls. There was an increase in the percentage of suppressor-cytotoxic T lymphocytes, CD8, and a proportionally larger increase in the number of CD8 cells expressing the class II activation marker. Most patients had an elevated number of CD2 cells which expressed the activation marker CDw26. The numbers of CD4 cells and the helper subset of CD4+CD29+ cells in patients with CFS were not different from those in controls. There was, however, a significant decrease in the suppressor inducer subset of CD4+ CD45RA+ cells. The number of B cells, CD20 and CD21, were elevated, as were the numbers of a subset of B cells which coexpressed CD20 and CD5. The patterns of immune marker abnormalities observed was compatible with a chronic viral reactivation syndrome.

Adult↗
PubMed1990

Allelic variants at insulin-receptor and insulin gene loci and susceptibility to NIDDM in Welsh population.

A cohort of 132 well-documented White Welsh non-insulin-dependent diabetic (NIDDM) subjects were genotyped for 5 restriction-fragment-length polymorphisms (RFLPs) at the insulin-receptor gene (IRG) locus and a polymorphic locus 5' to the insulin gene. There was no significant difference in RFLP frequencies between the NIDDM subjects and a group of 87 matched White control subjects. Paired haplotype analysis of the IRG RFLPs suggested a difference between NIDDM and control groups for the endonuclease combinations Bgl II-Rsa I and Bgl II-Xba I. Analysis of implied haplotypes defined by the endonucleases Bgl II, Rsa I, and Xba I revealed one haplotype to be more prevalent in the NIDDM group; whereas, another haplotype was associated with the control group (P less than 0.02). Subset analysis within the NIDDM cohort compared the metabolic response of NIDDM subjects with the differing IRG haplotypes to a standard meal tolerance test. Both groups showed equivalent basal and postprandial glucose excursions, but one group revealed a significantly exaggerated plasma insulin response compared with the other (P less than 0.05). This may reflect the influence of genetic variation at the IRG locus on insulin sensitivity in patients with NIDDM.

Adult↗
PubMed1990

Distention promotes platelet and leukocyte adhesion and reduces short-term patency in pig arteriovenous bypass grafts.

A pig model of autologous saphenous vein to common carotid artery bypass grafting was developed. An end-to-end anastomotic technique led to lower middle graft and distal turbulence. Saphenous veins were surgically prepared with or without distention at 600 mm Hg, implanted into the arterial circulation, and removed 2 hours later. Medial integrity was then assessed by adenosine triphosphate/adenosine diphosphate concentration ratio, and endothelial integrity, leukocyte and platelet adhesion by scanning electron microscopy. In grafts made with undistended vein adenosine triphosphate/adenosine diphosphate concentration ratio was not significantly lower (3.0 +/- 0.1, n = 32) than in freshly isolated vein (3.3 +/- 0.1, n = 26), endothelial cover was 98% +/- 1%, n = 6, and there was little platelet or leukocyte adhesion. In distended grafts adenosine triphosphate/adenosine diphosphate concentration ratio was reduced to 2.2 +/- 0.2 (n = 7, p less than 0.005), endothelial cover was reduced to 38% +/- 14% (n = 6, p less than 0.001), and there was extensive platelet and leukocyte adhesion to exposed subendothelium. In separate experiments graft patency measured at 1 to 5 weeks was significantly greater (96%, n = 25) when undistended vein was used than when distended vein was used (64%, n = 25, p less than 0.005). The data show that distention leads to medial and endothelial damage and that this is associated with increased platelet and leukocyte adhesion and with reduced early patency.

Adenosine Diphosphate↗
PubMed1989

Trisomy 14: a new entity within acute nonlymphocytic leukemia.

Three cases of acute nonlymphocytic leukemia with trisomy 14 as the sole chromosome abnormality are presented and it is suggested that this type of trisomy, either as an extra chromosome or an isochromosome, is phenotypically equivalent. The findings are presented in relation to other cases previously reported.

Aged↗
PubMed1989

Lack of involvement of the c-fms and N-myc genes by chromosomal translocation t(2;5)(p23;q35) common to malignancies with features of so-called malignant histiocytosis.

We report the molecular, cytogenetic, and immunologic characterization of three hematologic malignancies that contained characteristic t(2;5) chromosomal translocations. The clinicopathologic features in all three cases fit the disease spectrum of so-called malignant histiocytosis (MH). All cases expressed activation antigens including Ki-1 (CD 30), but no lineage-restricted pattern of cellular antigen expression was observed. Cell lines SUP-M2 and SU-DHL-1 established from two of the cases showed rearranged beta T-cell receptor (beta TCR) genes nonproductive of full-length beta TCR mRNA and therefore not helpful in unequivocal establishment of lineage derivation. The common cytogenetic feature was a reciprocal translocation between chromosomes 2 and 5, involving bands 2p23 and 5q35 near the reported chromosomal locations of the N-myc and c-fms genes, respectively. Normal-sized and truncated c-fms RNAs were observed in both cell lines, whereas no N-myc transcripts were detected. Sequence analysis of the truncated fms RNA showed that it consisted of the 3' half of the c-fms mRNA, but its derivation was not the result of a structural alteration of the c-fms gene. Our studies show that the t(2;5) does not involve the N-myc and c-fms protooncogenes and that this cytogenetic abnormality may be characteristic of a subset of primitive malignancies with an indeterminate lineage but with clinicopathologic features of so-called MH.

Adult↗
PubMed1989

SUP-HD1: a new Hodgkin's disease-derived cell line with lymphoid features produces interferon-gamma.

A new cell line, SUP-HD1, was established from the pleural effusion of a patient with nodular sclerosing Hodgkin's disease (NSHD). The SUP-HD1 cells had the characteristic morphology of Reed-Sternberg cells and contained acid phosphatase and nonspecific esterase. The cells lacked the Epstein-Barr virus (EBV) genome and reacted with monoclonal antibodies (MoAbs) against CD15 (Leu-M1), CD25 (Tac), CD71 (OKT9), Ki67, and HLA-Dr. However, the SUP-HD1 cells were nonreactive with MoAbs that specifically identify T lymphocytes, B lymphocytes, and macrophage/myeloid cells. Karyotype analysis of the cell line showed clonal abnormalities involving 1p13, 7p15, 8q22, and 11q23, chromosomal locations, at which breakpoints have been reported in HD. Southern blot analysis demonstrated rearrangement of the immunoglobulin heavy chain and kappa light chain genes as well as the gene for the beta chain of the T-cell receptor (TCR). Transcriptional analysis showed expression of RNAs for kappa light chain, interferon-gamma (IFN-gamma), and interleukin-2 receptor (IL-2R) but not IL-2. The SUP-HD1 cells lacked cytoplasmic and surface immunoglobulin heavy chain, but a small amount of cytoplasmic kappa light chain was detected. The presence of nuclear factor kappa B (NF kappa B), a B-lymphocyte-associated transcription factor, was demonstrated in stimulated and unstimulated cells. In addition, the SUP-HD1 cell line, produced IFN-gamma, a T-lymphocyte-associated lymphokine. Based on these data, the SUP-HD1 cells appear to be aberrant lymphocytes with characteristics of both activated B and T lymphocytes. Elaboration of lymphokines such as IFN-gamma by the malignant cells may represent one explanation for the unique clinical and pathologic features of HD.

Adult↗
PubMed1989

Mutations of the ras protooncogenes in chronic myelogenous leukemia: a high frequency of ras mutations in bcr/abl rearrangement-negative chronic myelogenous leukemia.

Seventy cases of chronic myelogenous leukemia (CML) were analyzed for the presence of ras mutations using polymerase chain reaction (PCR), oligonucleotide hybridization, and direct PCR sequencing. All cases had preceding cytogenetic and bcr rearrangement studies. Aberrant ras genes were detected in none of 39 patients with Philadelphia (Ph) chromosome or bcr/abl rearrangement positive chronic-phase CML and in only 1 of 18 patients in blast crisis, suggesting that ras mutations have little or no role in initiation or progression of common CML. Seven of 13, or 54% of patients with bcr/abl rearrangement negative chronic phase CML (atypical CML) harbored mutations in ras, however. This high incidence of ras mutations, together with the absence of bcr/abl rearrangement, provides evidence that atypical CML is an entity that is molecularly distinct from common CML. Moreover, the clinical characteristics and the high frequency of ras mutations suggest that atypical CML may constitute a subset of the myelodysplastic syndrome and may be best classified as a variant of chronic myelomonocytic leukemia (CMML).

Base Sequence↗
PubMed1989

Long-term growth of malignant thymocytes in vitro.

We report a new methodology for the long-term growth of malignant T-lymphoblasts from patients with T-cell acute lymphoblastic leukemia (T-ALL) and T-cell lymphoblastic lymphoma (T-LL). When malignant cells were cultured in the presence of insulin-like growth factor I under hypoxic conditions, cellular proliferation occurred that resulted in the establishment of immortal cell lines from ten of 12 patient tumors. Authenticity of each cell line was verified by a direct comparison of the immunophenotype, karyotype, and immunogenotype with the patient's tumor cells. This improved method of cell culture permits frequent establishment of cell lines from patients with T-ALL/T-LL, thereby aiding in analysis of thymocyte transformation and neoplasia.

Adolescent↗