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D L Mann

Publications and source records attributed to D L Mann.

At least 289 records · Page 16Linked to original sources

Comparison of soluble human and mouse transplantation antigens.

The molecular and chemical characteristics of membrane components bearing the major transplantation antigen systems in mouse (H-2) and man (HL-A) were compared and found to be strikingly similar. Kinetics of papain solubilization from cell membranes, gel filtration, and electrophoretic patterns of the alloantigenic components were found to be nearly identical. Comparable size heterogeneity of the solubilized materials was also demonstrated. Some differences in amino acid and carbohydrate content of the purified H-2 and HL-A alloantigenic materials were found. The general pattern of distribution of the amino acid residues, however, appears to be quite similar and indicate compositional relatedness in these materials. These physical and chemical similarities in the characteristics of molecules bearing the transplantation antigens are in accord with biologic studies indicating a comparable functional immunologic role for the mouse H-2 and human HL-A antigen systems. These studies support the view that the genes determining these major transplantation antigen systems may have evolved from a common precursor.

Amino Acids↗

Basic mechanisms of disease progression in the failing heart: the role of excessive adrenergic drive.

This review examines experimental evidence that suggests that excessive adrenergic stimulation of the heart may actually contribute to the untoward natural history of congestive heart failure. The basic mechanisms for catecholamine-mediated cardiac toxicity are discussed, as well as relatively new evidence that catecholamine-mediated toxicity is the result of beta-adrenoceptor-mediated cyclic adenosine monophosphate-dependent calcium overload of the cardiac myocyte. The studies reviewed herein provide a plausible biological rationale for the use of beta-adrenergic blocking agents in patients with heart failure.

Animals↗

Derivative fluorescence spectral analysis of polycyclic aromatic hydrocarbon-DNA adducts in human placenta.

Metabolic activation in humans of chemical carcinogens found in the environment results in the formation of carcinogen-DNA adducts in vivo. Some polycyclic aromatic hydrocarbon-DNA adducts in human DNA can be hydrolyzed under mildly acidic conditions to yield tetrahydrotetrol derivatives which may then be detected by synchronous fluorescence spectroscopy. In an analysis of human placental DNA, second derivative spectroscopy alone was unable to resolve the synchronous fluorescent signature for r-7,t-8,t-9,c-10-tetrahydroxy-7,8,9,10-tetrahydrobenzo[alpha]pyrene from a crude extract, because a complex array of other fluorescent materials was also present. Purification of the sample by a combination of chromatographic procedures including immunoaffinity chromatography and HPLC has now been shown to yield r-7,t-8,t-9,c-10-tetrahydroxy-7,8,9,10-tetrahydrobenzo[alpha]pyrene residues from human DNA that are spectroscopically pure at the second derivative level. Immunoaffinity columns were prepared with rabbit antiserum raised against DNA that had been modified with (+/-)-r-7,t-8-dihydroxy-t-9,10-epoxy-7,8,9,10-tetrahydrobenzo[alpha]pyre ne. This antiserum has now been shown to recognize DNA samples that have been modified with six different polycyclic aromatic hydrocarbon diol epoxides and is probably only specific for a broad spectrum of polycyclic aromatic hydrocarbon-DNA adducts. Adducts were eluted from the immunoaffinity columns, hydrolyzed with acid, and extracted into isoamyl alcohol, before being subjected to high-performance liquid chromatography. These experiments reveal important limitations of second derivative fluorescence spectroscopy as a tool in the analysis of complex environmental mixtures. Furthermore, they extensively define the ability of anti-benzo[alpha]pyrenediol epoxide-DNA antibodies to recognize different types of polycyclic aromatic hydrocarbon-DNA adducts.

Biotransformation↗

Cell lines producing human T-cell lymphoma virus show altered HLA expression.

Human T-cell leukaemia/lymphoma virus (HTLV) can be identified in fresh and cultured T-lymphocytes from patients with adult T-cell malignancies. HLA typing of the peripheral blood lymphocytes and cultured cell lines from the patient from which the virus was originally isolated suggested the expression of additional HLA-A and -B locus antigens on the HTLV positive cultured T-cells that were not present on the EBV transformed B-cell line or on the peripheral blood lymphocytes. Peripheral blood lymphocytes (PBLs) and T-cell lines established from patients and cord blood lymphocytes, infected with virus by co-culture with T-cell lines, were typed for HLA antigens with alloantisera and in addition tested for reactivity with a monoclonal antibody (4D12) which recognizes a polymorphic HLA class-I antigen. In all HTLV positive cells, with demonstrable provirus replication, altered HLA alloantigen expression was observed. This may be explained by the observations reported in the accompanying paper which shows homology between the envelope gene region of HTLV and the region of an HLA-B locus gene which codes for the extracellular portion of a class I histocompatibility antigen.

Antigens, Surface↗

SR compartment calcium and cell apoptosis in SERCA overexpression.

The relationship between SR Ca2+ ATPase (SERCA) activities, cell calcium level, SR calcium store and cell cycle events is not clearly understood. We studied SERCA overexpression in Cos cells using an adenovirus vector. Twofold increases in SERCA mRNA and in protein were correlated with a 2.3-fold and a 1.6-fold paralleled increase in SR calcium pump activity (R = 0.97 and R = 0.99 respectively). Dose-related apoptotic cell death was associated with SERCA overexpression (R = 0.92). When serum was reduced to 4%, cell apoptosis further increased from 20.7 +/- 4.8% to 47.5 +/- 12.9% (M+/-SD; P<0.05; n=3). Flow cytometry identified cell cycle arrest at the G2/M phase. The interleukin-1 converting enzyme (ICE) inhibitor z-VAD-fmk reduced apoptosis for low-, medium- and high-expressing constructs, whereas the CPP-32 inhibitor z-DEVD-fmk had no effect. Flow cytometry using Fluo-3 and Fura-Red revealed a 1.5-fold higher basal calcium and a 10-fold SR calcium overload. ICE inhibitor z-VAD-fmk did not alter calcium loading. An epitope-tagged SERCA mutant, which has no intrinsic Ca2+-pump activities, had a much smaller effect on the SR calcium. These findings suggest that SERCA2A overexpression has an intrinsic role in altering cell-cycle progression, augmenting cellular and SR calcium loading, and precipitating ICE protease-mediated apoptosis; this represents as a novel model for primary SR calcium overload and associated cell apoptosis.

Amino Acid Chloromethyl Ketones↗

Cytokines in heart failure: pathogenetic mechanisms and potential treatment.

Recent studies have shown that patients with heart failure overexpress a class of biologically active molecules, generically referred to as pro-inflammatory cytokines. This article will review recent clinical and experimental material that suggests that pro-inflammatory cytokines such as tumor necrosis factor-alpha (TNF-alpha), interleukin-1 (IL-1), and interleukin-6 (IL-6) may play a role in the pathogenesis of congestive heart failure. In addition, we will review recent studies that suggest that antagonizing cytokines may represent a novel target for heart failure therapy.

Animals↗

Liquid chromatographic analysis of vitamin B6 in soy-based infant formula.

A liquid chromatographic (LC) method is described for determination of total vitamin B6 in soy-based infant formula. Total vitamin B6 is quantitated by using ion-pair LC after precolumn transformation of phosphorylated and free vitamers into pyridoxol. The limit of detection is 0.3 ng and the limit of quantitation is 1.0 ng on-column (injection volume = 100 microL). Linear response ranged from 39 to 616 ng/mL (r2 = 0.99986). Analysis of a soy-based infant formula control fortified at 6 different concentration levels gave recoveries that averaged 104%. Assay of SRM 1846 gave results within the certified range (8.6 +/- 0.086 mg/kg versus the certified value of 8.4 +/- 1.0 mg/kg). The method provides a rapid and specific assay for the analysis of total vitamin B6 in fortified soy-based infant formula.

Calibration↗

Histocompatibility antigen combinations in rheumatoid arthritis.

The frequencies of HLA-A, -B, -C, DR and MT lymphocyte alloantigens in clinical and serologic subsets of rheumatoid arthritis (RA) were determined in 65 Caucasian patients with definite or classical disease and compared to frequencies observed in normal individuals. The elevation in frequency of several antigens controlled by different genes in the major histocompatibility complex (MHC) suggested that combinations of antigens may be associated with RA. Significant associations were found for HLA-A1-DR4 and A1-MT2 (p less than 0.001), Bw40-DR4 (p less than 0.002) and Cw3-DR4 (p less than 0.001). The results indicate that combinations of genes in the MHC are influential in predisposing to RA.

Arthritis, Rheumatoid↗

Human lymphocyte antigens characterizing psoriatic arthritis and its subtypes.

We performed human lymphocyte alloantigen determinations in patients with psoriatic arthritis (PsPA) who were clinically classified into arthritic subtypes and disease severity. The total PsPA group demonstrated elevations of HLA-BW38, CW6, DR4 when compared with controls (p less than 0.001). Severe arthritics have increased DR4 frequency when compared with less severe arthritics (p less than 0.02). Those with mild disease have increased A3, B7 frequency which was absent in patients with moderate or severe arthritis. Rheumatoid-like PsPA patients have increased DR4, B40 frequencies; those with spondylitis, B27, CW1. PsPA is associated with many genes in the major histocompatibility complex. Distinct groups of patients with PsPA as determined by type and severity are identifiable by the presence of specific human lymphocyte antigens.

Adolescent↗