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Biomedical subjects

P Baker

Publications and source records attributed to P Baker.

At least 127 records · Page 7Linked to original sources
PubMed1989

2'-5' oligoadenylate synthetase and its relationship to HLA and genetic markers of insulin-dependent diabetes mellitus.

Cytokines and their related enzyme pathways may play a part in the development of insulin-dependent diabetes mellitus (IDDM). We have therefore studied the activity of the enzyme 2'-5' oligoadenylate synthetase (which is induced by both interferon and the tumour necrosis factors) in circulating mononuclear cells from 40 subjects with IDDM and 32 healthy control subjects. There was no difference in mean basal enzyme activity between the two groups. A polymorphism of the 2'-5' oligoadenylate synthetase gene, not previously described, was found using the restriction enzyme Bam HI. There was no association of 2'-5' oligoadenylate synthetase genotypes with IDDM, but there was a significant correlation between basal 2'-5' oligoadenylate synthetase activity and 2'-5' oligoadenylate synthetase genotypes. Significantly higher mean basal levels of 2'-5' oligoadenylate synthetase activity were associated with HLA-DQA 4.6 phenotype (determined using the restriction enzyme Taq 1 and a DQA probe) and HLA-DR3 (determined serologically), whereas significantly lower mean levels of enzyme activity were associated with HLA-DQA 5.5 and HLA-DR7, in both IDDM and control subjects. An analysis of variance confirmed that these associations were independent 2'-5' oligoadenylate synthetase genotype. Likewise, a significantly higher mean level of enzyme activity was associated with the heterozygous 1/3 insulin-related genotype in the IDDM subjects only. This study therefore suggests that the possession of certain HLA haplotypes might be associated with differing levels of basal 2'-5' oligoadenylate synthetase activity.

2',5'-Oligoadenylate Synthetase↗
PubMed1989

Kinetics of the aspartyl transpeptidation of daptomycin, a novel lipopeptide antibiotic.

Two degradation products of the lipopeptide antibiotic, daptomycin, were identified and the reaction pathway and kinetics were delineated in aqueous solution at 60 degrees C, pH range 3 to 8 and ionic strength 0.01. The degradation products were 1) a succinimido intermediate (anhydro-daptomycin) formed by attack of side-chain carbonyl on the peptide-bond nitrogen in the asp-gly sequence and 2) a beta-asp daptomycin isomer formed by rehydration of the anhydrodaptomycin succinimide. This aspartyl transpeptidation pathway was found to be reversible. Formation of the anhydrodaptomycin from either daptomycin or beta-asp daptomycin was pH dependent but the pH-rate profiles for anhydrodaptomycin formation were not mechanistically interpretable. The pH-rate profiles for the formation of daptomycin or beta-asp daptomycin from the anhydrodaptomycin were linear with slopes = 1, which is consistent with nucleophilic hydroxide ion attack of the succinimido intermediate at either the alpha-carbonyl, giving rise to the beta-asp daptomycin, or the beta-carbonyl, giving rise to daptomycin.

Aspartic Acid↗
PubMed1988

Platelets mediate neutrophil-dependent immune complex nephritis in the rat.

Neutrophils and platelets are frequently present in glomeruli in immune glomerulonephritis (GN). No role for the platelet in acute neutrophil-mediated renal injury has been defined. We investigated a neutrophil-mediated model of subendothelial immune complex GN in the rat. Rats were platelet-depleted (mean platelet less than 10,000/microliter) with goat anti-platelet IgG before induction of GN by the renal artery perfusion of concanavalin A followed by anti-concanavalin A IgG. Platelet-depletion resulted in a significant reduction in albuminuria (7 +/- 2 vs. 55 +/- 10 mg/24 h) and fractional albumin excretion (0.045 +/- 0.01 vs. 0.410 +/- 0.09) compared with controls. The decrease in albuminuria was not due to differences in blood or glomerular neutrophil counts, complement, renal function, or glomerular antibody binding. Platelet-depleted rats had equivalent subendothelial deposits and glomerular endothelial cell injury but had minimal platelet infiltrates and fibrin deposition compared with controls. These studies demonstrate a role for platelets in mediating acute neutrophil-induced glomerular injury and proteinuria in this model of GN.

Animals↗
PubMed1988

Morphologic correlates of glomerular oxidant injury induced by the myeloperoxidase-hydrogen peroxide-halide system of the neutrophil.

Neutrophilic polymorphonuclear leukocytes can mediate glomerulonephritis by releasing reactive oxygen species such as H2O2. We have previously demonstrated that H2O2-mediated glomerular injury can be potentiated by reaction with polymorphonuclear leukocyte myeloperoxidase (MPO). When MPO was perfused into renal arteries of rats, it bound to the glomerular capillary wall due to its cationic charge. Subsequent perfusion with nontoxic concentrations of H2O2 and halides resulted in acute glomerular injury, halogenation of the glomerular basement membrane, and proteinuria. The studies reported here document the morphologic changes that accompany MPO-mediated glomerular injury. Acutely, there is severe injury to the endothelium with cell swelling and lysis. Within 10 minutes, a marked platelet influx occurs. Platelets frequently occlude capillary lumens and bind to areas of denuded glomerular basement membrane where platelet degranulation results. By 4 days, the platelet infiltration has ceased, and a reparative phase develops characterized by marked proliferation of resident endothelial cells and possibly mesangial cells. By 21 days postperfusion, the glomerular lesion had largely resolved. In contrast, control rats perfused with MPO alone, H2O2 alone, or buffered saline alone demonstrate minimal glomerular injury at all times studied. MPO-mediated glomerular disease results in endothelial and mesangial cell injury, activation of platelets, and a subsequent proliferative response. These morphologic changes resemble those seen in several forms of inflammatory and proliferative glomerulonephritis in man.

Animals↗
PubMed1987

Transplantation of cultured autologous epidermis to a patient with burns.

Explant-derived cultured autologous epidermis was used as a graft in a 41-year-old female patient with burns, the first subject in a clinical trial of the technique. A small full-thickness biopsy specimen which was taken on Day 2 of the hospital admission was used to initiate epidermal cultures, four of which were grafted onto the patient's back and right leg 29 and 35 days later. Three of these epidermal cultures engrafted successfully, in spite of infection with Pseudomonas aeruginosa, which resulted in the loss of some of the conventional, split-thickness meshed autografts that were applied concurrently. The fourth graft, which may have been oriented incorrectly onto the graft bed, was largely unsuccessful, and only small islets of epithelial cells remained after 10 days. The successful grafts produced full-thickness, epidermal coverage with a good cosmetic result and little evidence of contraction during a six-months' follow-up.

Adult↗
PubMed1987

Expression, purification and characterization of recombinant murine granulocyte-macrophage colony-stimulating factor and bovine interleukin-2 from yeast.

Expression and secretion of two lymphokines, murine granulocyte-macrophage colony-stimulating factor (MuGM-CSF) and bovine interleukin-2 (BoIL-2), to levels of 50-60 mg per liter were achieved by placing these cDNAs in a Saccharomyces cerevisiae expression vector that utilized the yeast alcohol dehydrogenase-2 promoter and alpha-factor leader peptide. These lymphokines were purified to homogeneity by direct application of the crude yeast medium to reversed-phase high-performance liquid chromatography. Despite the fact that both lymphokines contain at least one N-glycosylation site and have identical N-terminal residues (Ala-Pro-Thr), recombinant (R) GM-CSF was found to be heterogeneously glycosylated by yeast while RBoIL-2 was secreted without glycosylation. Additionally, approximately 40% of the RGM-CSF was found to be proteolytically cleaved after the second amino acid residue, while RBoIL-2 was found to be intact.

Animals↗
PubMed1987

Participation of the myeloperoxidase-H2O2-halide system in immune complex nephritis.

Neutrophils (PMNs) mediate injury in experimental glomerulonephritis (GN) in part via the release of reactive oxygen species, particularly hydrogen peroxide (H2O2). Recent kidney perfusion studies demonstrate that H2O2 can cause glomerular injury by reaction with halides in the presence of the PMN cationic enzyme myeloperoxidase (MPO) to form oxidants which can oxidize and halogenate tissue. We sought evidence for participation of the MPO system in a model of PMN-mediated immune complex (IC) GN. A PMN-dependent model of GN was developed in rats by perfusing the renal artery with concanavalin A followed by anticoncanavalin A antibody. PMN depletion abolished glomerular PMN infiltration and significantly reduced proteinuria (35 +/- 7 mg/day vs. 113 +/- 10, P less than 0.001). Rats that received Na125I (5.0 microCi) three and six hours following disease induction had more 125I incorporation in glomeruli and GBM at 48 hours than similarly treated rats that were PMN depleted (1200 cpm vs. 88 cpm, P less than 0.01). Glomerular iodination could not be demonstrated in a PMN-independent model of nephrotoxic nephritis induced with noncomplement fixing anti-GBM antibody. These data indicate that this model of PMN-mediated IC GN is associated with activation of the MPO-H2O2-halide system, which may participate in mediating glomerular injury.

Animals↗
PubMed1987

The prognosis of hypertension according to age at onset.

Data from a program for hypertension screening and follow-up were used to study the relationship between age at onset of hypertension and the risk of cardiovascular complications. The risk for hypertensive subjects, compared with normotensive subjects of similar age, declined significantly as age of onset increased from 40 to 69 years. This pattern was not explained by differences in initial severity of hypertension, control of hypertension, obesity, smoking, or alcohol consumption. A sex-specific analysis showed that the pattern was confined to male subjects, but it is argued that it might be seen in female subjects if data for women of more advanced age were available. Further lines of investigation of this interesting phenomenon are proposed.

Adult↗
PubMed1985

Severe compression neuropathy following sudden onset of parkinsonian immobility.

Prolonged immobility with adoption of unusual fixed body postures may lead to compression neuropathy. Although parkinsonism has not been considered to predispose to nerve compression, we report three patients with Parkinson's disease and on-off motor fluctuations who developed severe compression neuropathy following a sudden onset off period. The stereotyped posture assumed by parkinsonian patients during an off period appears to make them especially prone to injury of the radial nerve in the upper arm and the brachial plexus.

Aged↗
PubMed1985

A serum independent medium effective in all aspects of hybridoma technology and immunological applications.

KC 2000 TM is a serum-free medium designed and developed for use in all phases of hybridoma technology providing maximum growth and antibody production. This unique medium provides consistent results as its performance is not affected by variation found in serum. In addition, the use of KC 2000 TM reduces the risk of contamination of cultures by mycoplasma and viruses which may be present in low concentrations in serum. Antibody production and assays are performed in KC 2000 TM without high concentrations of interfering proteins. Only those proteins necessary to produce maximum performance in all hybridoma applications are present (250 micrograms protein/ml). Extensive testing has shown that this serum-free medium yields maximum results in all aspects of hybridoma technology, including the generation of antibody secreting hybridomas, as well as their subcloning. With a single exception, all cell lines tested could be transferred directly from medium containing serum into KC 2000 TM. Consistent growth and antibody production was maintained during subsequent passaging of these cells. These results show that KC 2000 TM is unique among serum-free media as it is the only serum-free medium that can be successfully utilized in the selection of HAT-resistant hybrid cell clones after use of a single type of medium throughout the entire process of development and maintenance of hybridoma cell lines.

Animals↗
PubMed1985

Effect of alterations in glomerular charge on deposition of cationic and anionic antibodies to fixed glomerular antigens in the rat.

Reduction of the negative charge of the glomerular capillary wall alters its charge- and size-selective properties. To investigate the effect of alteration in glomerular charge properties on antibody localization, we prepared cationic and anionic fractions of antibodies to subepithelial and glomerular basement membrane (GBM) antigens, and compared their deposition in normal rats and rats treated with protamine sulfate or aminonucleoside of puromycin to reduce capillary wall charge. IgG antibodies were eluted from kidneys of rats with active Heymann's nephritis (AICN), passive Heymann's nephritis (PHN), or anti-GBM nephritis (NTN), separated into cationic and anionic fractions, and radiolabeled with iodine 125 or iodine 131. Relative antibody content of each fraction was determined by incubation with an excess of glomerular antigen. Varying amounts of cationic and anionic IgG eluted from kidneys of rats with AICN or PHN were injected into 24 normal or protamine sulfate-treated rats. Glomerular binding of all antibodies was highly correlated with IgG delivery to the kidney. The ratio of cationic to anionic antibody deposited in the glomeruli of normal rats after 4 hours was 1.08 +/- 0.07 for AICN eluate and 0.37 +/- 0.04 for PHN eluate. The ratios were not significantly different in animals pretreated with protamine sulfate (1.15 +/- 0.06 and 0.44 +/- 0.06, respectively; P greater than 0.05). Varying amounts of cationic and anionic IgG eluted from kidneys of rats with NTN were injected into 10 normal rats and four rats treated with aminonucleoside of puromycin. Glomerular binding of antibody was again highly correlated with IgG delivery to the kidney. The ratio of cationic to anionic antibody deposited in the glomeruli of normal rats after 1 hour was 1.03 +/- 0.06, and was not significantly altered in rats treated with aminonucleoside of puromycin (1.05 +/- 0.03, P greater than 0.5). Proteinuria in PHN rats was also unaffected by treatment with protamine sulfate for 5 days (controls: 68 +/- 21 mg/day; protamine sulfate-treated: 65 +/- 14 mg/day; n = 25, P greater than 0.08). These results demonstrate that treatment to reduce glomerular polyanion does not significantly alter the ratio of cationic to anionic antibodies to fixed glomerular antigens that deposit in the glomerulus, or reduce proteinuria caused by deposition of antibody to a fixed subepithelial antigen.

Animals↗
PubMed1981

Antiphosphocholine antibodies found in normal mouse serum are protective against intravenous infection with type 3 streptococcus pneumoniae.

The antiphosphocholine (PC) antibody in normal mouse sera (NMS) provides protection against intravenous infection with encapsulated strain WU2 of type 3 Streptococcus pneumoniae. Mice unable to make anti-PC antibody, as a result of suppression with anti-T-15 idiotype or inheritance of the xid gene of CAB/N mice, are highly susceptible to infection with strain WU2. Mice inheriting the xid gene can be protected with NMS from immunologically normal mice or with IgM hybridoma anti-PC antibody. The protective effect of NMS can be removed with PC-containing immunoabsorbents.

Animals↗
PubMed1981

Twelve months' experience with continuous ambulatory and intermittent peritoneal dialysis.

After a one-year experience with a continuous ambulatory and long-term intermittent peritoneal dialysis (CAPD and IPD, respectively) program in a Veterans Administration hospital, both forms of dialysis provided excellent biochemical control of the patients' conditions. The major drawback to peritoneal dialysis as opposed to hemodialysis is the high rate of rehospitalization resulting from peritonitis or problems related to the peritoneal catheter. The incidence of peritonitis was one episode per 4.1 patient months in CAPD and one episode per 7.3 patient months in IPD. Recurrent episodes of peritonitis in a given patient were associated with a decrease in the serum albumin level. Blood values for BUN, creatinine, serum electrolytes, calcium, and phosphorus, however, were not altered. To date, CAPD appears to be an effective alternative form of dialytic therapy.

Adult↗