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Biomedical subjects

D L Murray

Publications and source records attributed to D L Murray.

At least 37 records · Page 2Linked to original sources

Screening maternal serum alpha-fetoprotein levels and human parvovirus antibodies.

The association between gestational infection with human parvovirus (B19) and fetal loss has increased interest in this virus and demand for diagnostic testing. However, serological assays for B19 are not yet widely available. Maternal serum alpha-fetoprotein (MSAFP) testing is commonly used during the second trimester to screen for various fetal defects. We attempted to determine whether an elevated level of MSAFP would be an appropriate indication for B19-specific tests. Over a 26-month period, MSAFP tests were performed at Michigan State University for 21 392 women. Sera remaining after that testing were stored frozen. Of these, 22 cases samples--from women with MSAFP levels greater than 3.0 multiples of the median (MOM) and pregnancies that ended in fetal loss--and 44 matched control samples--from women with MSAFP levels greater than 0.4 and less than 2.2 MOM and live births at term--were tested for B19 antibodies. None of the 66 samples was IgM positive, while 33 (50 per cent) were IgG positive. The presence of IgG was not significantly associated with case or control status (matched odds ratio = 0.77, 95 per cent confidence interval 0.28-2.11). These findings are consistent with other studies indicating prior infection in approximately half of adults and suggest that elevated screening MSAFP levels, in the absence of other evidence of B19 infection, should not prompt B19-specific testing.

Adult↗

Passive transfer of hepatitis antibodies during intravenous administration of immune globulin.

We studied the effect of intravenous immune globulin (IVIG) infusion on the levels of hepatitis B and C antibodies in 10 premature babies. All four tested lots of a commercially purchased IVIG preparation were found to contain substantial amounts of hepatitis B core and hepatitis C antibodies. Our results show that passive transfer of hepatitis B and C virus antibodies occurred after IVIG infusion, and that the levels were dependent on the quantity of IVIG given. When assessing neonates for hepatitis, the factor of receipt of blood products, including IVIG, needs to be considered to interpret laboratory results.

Gestational Age↗

Structure of toxic shock syndrome toxin 1.

The three-dimensional structure of toxic shock syndrome toxin 1 (TSST-1) from Staphylococcus aureus has been determined and refined to an R value of 0.226 for data between 8- and 2.5-A resolution. Overall, the structure of TSST-1 is similar to that of another superantigen, staphylococcal enterotoxin B (SEB). The key differences between these molecules are in the amino termini and in the degree to which a long central helix is covered by surface loops. The region around the carboxyl end of this central helix is proposed to govern the superantigenic properties of TSST-1. An adjacent region along this helix is proposed to be critical in the ability of TSST-1 to induce toxic shock syndrome.

Amino Acid Sequence↗

Toxic shock syndrome toxin-secreting Staphylococcus aureus in Kawasaki syndrome.

Kawasaki syndrome (KS), the main cause of acquired heart disease in children, is associated with the selective expansion of V beta 2+ T cells in peripheral blood. Our study suggests that KS may be caused by a superantigen--a staphylococcal or streptococcal toxin. Bacteria were cultured without knowledge of their origin, from the throat, rectum, axilla, and groin of 16 patients with untreated acute KS and 15 controls. Bacteria producing toxins were isolated from 13 of 16 KS patients but from only 1 of 15 controls (p < 0.0001). Toxic shock syndrome toxin (TSST) secreting Staphylococcus aureus was isolated from 11 of the 13 toxin-positive cultures, and streptococcal pyogenic exotoxin (SPE) B and C were found in the other 2. These toxins are known to stimulate V beta 2+ T cells. All TSST-producing KS isolates were tryptophan auxotrophs indicating they were clonally related. S aureus isolates from acute KS patients were unusual because they produced less lipase, haemolysin, and protease compared to other isolates (p < 0.01). S aureus colonies from KS patients were white, and could be easily mistaken for coagulase-negative staphylococci, whereas colonies of non-KS isolates were gold. These observations suggest that the expansion of V beta 2+ T cells in most patients with KS may be caused by a new clone of TSST-producing S aureus, and, in a minority of patients, SPEB-producing or SPEC-producing streptococci.

Bacterial Proteins↗

Serologic markers of viral hepatitis A, B, C, and D in patients with hemophilia.

Forty-one patients with hemophilia A were studied for the prevalence of serological markers for hepatitis A, hepatitis B, hepatitis C (non-A and non-B hepatitis), and delta hepatitis (hepatitis D). Ten of 41 (24.4%) patients demonstrated hepatitis A antibody and 31 of 41 (75.6%) patients had a serologic marker for previous hepatitis B infection; four of these 31 patients (13%) also demonstrated antibody to delta agent (hepatitis D). Thirty-seven of 41 (90.2%) patients demonstrated antibody for hepatitis C. Nine of 31 (29%) patients with a hepatitis B marker (no hepatitis B vaccinees) were negative for anti-HBc but positive for anti-HBs; all of these nine patients were HIV antibody positive, although they had no overt immunodeficiency. Twenty-six of 41 (63.5%) patients were HIV antibody positive. Of HIV antibody positive patients, 27%, 88%, and 100% demonstrated evidence of a previous hepatitis A, hepatitis B, or hepatitis C, respectively. Of HIV antibody negative patients; 20%, 53%, and 73% of the patients demonstrated evidence of a previous hepatitis A, hepatitis B, or hepatitis C infections, respectively. The difference between HIV antibody positive and HIV antibody negative groups was not significant for hepatitis A but was significant for hepatitis B (P < 0.001) and hepatitis C (P < .001). Of the 31 patients with a hepatitis B serologic marker, all had antibody to hepatitis C. Of 10 patients, without a hepatitis B serologic marker, only 6 (60%) had antibody to hepatitis C.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Growth and analysis of crystal forms of toxic shock syndrome toxin 1.

Native toxic shock syndrome toxin 1 (TSST-1) purified from Staphylococcus aureus has been crystallized in four different forms. The highest resolution data (2.05 A) was collected from orthorhombic crystals belonging to the space group C222(1). The unit cell dimensions are a = 108.7 A, b = 177.5 A, c = 97.6 A. Rotation function analysis of this form indicates that there is trimer of toxin molecules in the asymmetric unit with a local 3-fold axis parallel to the crystallographic c axis. Crystals of a double mutant of TSST-1 have been grown which has a single molecule in the asymmetric unit and diffract to 1.9 A. The space group is P2(1) with unit cell parameters of a = 44.4 A, b = 34.0 A, c = 55.2 A, beta = 93.0 degrees.

Bacterial Toxins↗

The relationship between aqueous humor flow and anterior chamber protein concentration in rabbits.

PURPOSE: Protein concentration in the anterior chamber of noninflamed eyes is determined by three factors: the rate of protein entry into the aqueous humor (AH), the removal rate by bulk flow of AH, and the anterior chamber volume. On the basis of observations by previous investigators and the authors' computational modeling, it was hypothesized that a direct reciprocal relationship exists between aqueous flare and AH flow. This relationship was studied in pigmented rabbits, under several conditions, to determine the validity of the hypothesis that changes in aqueous flare intensity reflect variations in AH flow rate. METHODS: Aqueous flare and AH flow were measured in rabbits entrained to a 12 hr light: 12 hr dark cycle, starting at 6 AM, which subsequently was phase-shifted 6 hr earlier to allow measurements over the light-to-dark transition period. AH flow rates were determined fluorophotometrically using the clearance method after corneal deposition of fluorescein. A Kowa FC1000 cell/flare meter was used to measure aqueous flare. Predictions of anterior chamber protein concentration were made using a computer model of plasma-derived protein diffusion into AH. The response to changes primarily of AH flow were evaluated by concurrently determining flare and flow before and after administration of intravenous acetazolamide. RESULTS: Aqueous flare decreased 40% during constant light and 47% over the light-dark transition in a parallel, monophasic manner. AH flow did not change significantly under either condition. In contrast, acetazolamide-induced changes in AH flow resulted in reciprocal changes in flare that could be simulated with the computer model through flow parameter changes alone. CONCLUSIONS: Anterior chamber protein concentration in rabbits appears to be modulated both by factors affecting AH flow and protein entry into the aqueous. Thus, in rabbits, changes in aqueous flare do not necessarily reflect AH flow changes.

Acetazolamide↗

Hazards of closed pesticide mixing and loading systems: the paradox of protective technology in the Third World.

In studies in developing countries, closed systems for mechanically mixing and loading hazardous pesticides have been shown to reduce exposure to workers. To evaluate the efficacy of closed systems in preventing worker exposure in the developing world, a cross sectional study was conducted at rural crop dusting airports in the cotton growing region of Nicaragua. Worker exposure was evaluated by measuring the activity of erythrocyte cholinesterase in the field with a new design battery operated colorimeter. The 10 mixer loaders at four airstrips with closed systems were compared with the 16 mixer loaders at four airstrips where pesticides were hand poured. Paradoxically, cholinesterase activity was 1.1 IU/ml blood (95% Cl 0.49-1.8) lower (inhibited) among workers in airstrips with closed systems than among workers hand pouring insecticides, after adjusting for weight of organophosphates sprayed in the past 14 days, and for prior training in safe use of pesticides. Mixer loaders with prior training had cholinesterase activity 0.83 IU (95% Cl 0.30-1.4) higher than untrained workers, and the weight of organophosphates sprayed was also a statistically significant predictor in the model. Unfortunately, management viewed the closed systems primarily as a production tool, rather than as a way to protect workers. Airstrips with closed systems were able to apply an average of 3250 lb organophosphates per worker in the 14 days before the survey compared with 849 lb per worker in airstrips without closed systems. Only three of 10 mixer-loaders at airstrips with closed systems had received formal training in safer use of pesticides. Because of shortage of personnel and transport, it was difficult for the responsible government agencies to train workers adequately and to enforce pesticide health and safety standards at multiple dispersed worksites.

Cholinesterase Inhibitors↗

Chloroplasts of Arabidopsis thaliana homozygous for the ch-1 locus lack chlorophyll b, lack stable LHCPII and have stacked thylakoids.

We are interested in the mechanism of insertion of proteins into the chloroplast thylakoid membrane and the role that accessory pigments may play in this process. For this reason we have begun a molecular analysis of mutant plants deficient in pigments that associate with thylakoid membrane proteins. We have characterized plants that are homozygous for the previously isolated, recessive mutation chlorina-1 (ch-1) of Arabidopsis thaliana. Despite the lack of chlorophyll b and light-harvesting proteins of photosystem II (LHCPII) near normal levels of LHCPII mRNA are found in the mutant, in contrast to LHCPII mRNA levels in carotenoid-deficient mutants. The LHCPII mRNA of chlorina-1 plants can be translated in vitro so it is likely that LHCPII is not stable in ch-1 plants. Moreover, the thylakoid membranes of ch-1 plants remain appressed even though LHCPII levels are drastically reduced.

Chlorophyll↗

Age-related cysteine uptake as rate-limiting in glutathione synthesis and glutathione half-life in the cultured human lens.

The study included human lenses of ages ranging from newborn to 92 years. Protein-free reduced glutathione decreased 14-fold, whereas protein-free oxidized glutathione increased 2.6-fold with increasing age. L-Cyst(e)ine uptake g-1 lens of very old cultured lenses decreased 70% from that exhibited in newborn lenses, demonstrating a marked decline of L-cyst(e)ine uptake as a function of age. In these same lenses the synthesis of reduced glutathione (mumol g-1 lens) decreased 73% with age. It was concluded that the glutathione decrease observed in the aging human lens was associated with decreased uptake of L-cyst(e)ine, decreased glutathione synthesis and possibly an increase in protein-free oxidized glutathione. The high correlation of L-cyst(e)ine uptake and glutathione synthesis supports the hypothesis that L-cyst(e)ine uptake is a rate-limiting factor of glutathione synthesis in the intact human lens. By the use of buthionine sulfoximine, the half-life of glutathione was estimated to be 90 hr in the cultured human lens.

Adolescent↗

Preretinal pH changes in the rabbit under conditions of light and dark.

Preretinal pH was measured in the avascular region of 19 rabbit retinas during alternating cycles of light and dark, using a miniature, needle-type pH electrode. In 14 experiments with the rabbits breathing room air, cyclic changes in pH, decreasing in the dark and increasing in the light, were observed. The transition from light to dark caused a mean pH decrease of 0.047 +/- 0.029 U (n = 14). An inversion of the light/dark pH response was observed in five experiments. In three of these, the effect was induced by having the rabbits breathe 100% O2. In the five rabbits showing a reversed response, a mean pH increase of 0.034 +/- 0.025 pH U was observed in the dark; light-ON caused a decrease of 0.035 +/- 0.025 pH U. The direction of the preretinal pH change is thought to be the net effect of light/dark-induced changes in the metabolism of the photoreceptors and inner retinal layers (defined for the purpose of this paper as the region between the outer synaptic layer and the inner limiting membrane). In six separate experiments, retinal metabolism was assessed by measuring preretinal PO2 during alternating cycles of light and dark while the rabbits breathed room air. Oxygen tension declined from a mean of 14.5 +/- 6.2 (S.D.) mmHg in the light to 10.1 +/- 5.4 (S.D.) mmHg in darkness, and increased from a mean of 10.9 +/- 5.1 (S.D.) mmHg in darkness to 15.4 +/- 5.8 (S.D.) mmHg in the light. The time courses of the pH and the PO2 changes were similar.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Effect of timolol on human retinal, choroidal and optic nerve head circulation.

In a double-masked, randomized, placebo-controlled study, we evaluated the effect of topical timolol maleate 0.5% on the retinal, choroidal, and optic nerve head circulation in 5 healthy volunteer subjects. Changes in the pulsatile component of choroidal blood flow (PCBF) were determined from measurements of the ocular pulse wave. Changes in the retinal arterial blood flow rate (RBF) and optic nerve head capillary blood speed (CBS) were determined by laser Doppler velocimetry and monochromatic photography. In timolol-treated eyes, PCBF decreased by 32 +/- 12% (p = 0.0007). Changes in RBF and CBS were not statistically significant. In the contralateral placebo-treated eyes, PCBF decreased by 15 +/- 8% (p = 0.006) and RBF increased by 18 +/- 10% (p = 0.002). The change in CBS was not statistically significant.

Administration, Topical↗

Triage decisions in child care for sick children.

Child-care centers for children with mild, acute communicable, and noncommunicable illnesses are beginning to evolve. Few states have enacted regulations concerning the policies and procedures under which child-care centers for sick children operate. These centers should have policies regarding the triage and care of ill children that promote the safety of all children and staff at the center. As part of the establishment of regulations for the Michigan Department of Social Services, Lansing, a triage model has been developed that provides a means of standardizing the screening process used to admit mildly ill children to such centers. We present pilot guidelines for use by center personnel, discuss considerations inherent in formulating triage policy for child-care centers for sick children, and provide a starting point for those attempting to standardize regulations governing child-care centers for sick children.

Child Day Care Centers↗

Cysteine and glutathione metabolism in organ-cultured rat corneas.

The capability of organ-cultured rat corneas to metabolize cysteine and synthesize glutathione was assessed by use of radioactive L-cyst(e)ine. Metabolites from protein-free tissue extracts were separated and quantified by HPLC, using radioisotope and ultraviolet detectors. Most of the radioactivity detected in the rat cornea was found in three areas of the HPLC elution profile: 1) reduced glutathione, 2) cystine and 3) in a rapidly eluting area (the 'five-minute' area) consisting of several unidentified peaks. The proportion of radioactivity found within the five-minute area increased with time of incubation and became the dominant radioactive peak area by 48 hours of incubation. In contrast to rat lens extracts, the synthesis of glutathione in rat cornea formed a minor portion of the L-cysteine metabolic products. The unlabeled reduced glutathione concentration was relatively stable over a 48-hour incubation period. Synthesis of glutathione was prevented by 0.3 mM buthionine sulfoximine, resulting in more than 90% of the radioactivity being contained in the five-minute peak area. Inhibition of glutathione synthesis allowed the estimation of glutathione's half-life to approximate 10.5 hours in the organ-cultured rat cornea.

Animals↗