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Biomedical subjects

C Hoffman

Publications and source records attributed to C Hoffman.

At least 55 records · Page 3Linked to original sources

Marital status of caregiving daughters and co-residence with dependent parents.

The role of caregiving daughters' marital status is examined as it relates to their sharing households with disabled elderly parents. Married daughters fared best in well-being, income, and social support. Never-married women were the most likely to have never moved out of the parental home. Separated/divorced caregivers, more than the married and widowed, had moved into the parent's home rather than the reverse and widowed daughters had lived in re-formed joint households longest. The main reason for re-forming shared households was disability of the parent. Among other reasons were death or withdrawal of previous caregiver and financial problems, with separated/divorced daughters the most likely to mention finances.

Adaptation, Psychological↗

Refined crystal structures of glucoamylase from Aspergillus awamori var. X100.

The refined crystal structures of a proteolytic fragment of glucoamylase from Aspergillus awamori var. X100 have been determined at pH 6 and 4 to a resolution of 2.2 A and 2.4 A, respectively. The models include the equivalent of residues 1 to 471 of glucoamylase from Aspergillus niger and a complete interpretation of the solvent structure. The R-factors of the pH 6 and 4 structures are 0.14 and 0.12, respectively, with root-mean-square deviations of 0.014 A and 0.012 A from expected bondlengths. The enzyme has the general shape of a doughnut. The "hole" of the doughnut consists of a barrier of hydrophobic residues at the center, which separates two water-filled voids, one of which serves as the active site. Three clusters of water molecules extend laterally from the active site. One of the lateral clusters connects the deepest recess of the active site to the surface of the enzyme. The most significant difference in the pH 4 and 6 structures is the thermal parameter of water 500, the putative nucleophile in the hydrolysis of maltooligosaccharides. Water 500 is associated more tightly with the enzyme at pH 4 (the pH of optimum catalysis) than at pH 6. In contrast to water 500, Glu179, the putative catalytic acid of glucoamylase, retains the same conformation in both structures and is in an environment that would favor the ionized, rather than the acid form of the side-chain. Glycosyl chains of 5 and 8 sugar residues are linked to Asparagines 171 and 395, respectively. The conformations of the two glycosyl chains are similar, being superimposable on each other with a root-mean-square discrepancy of 1.9 A. The N-glycosyl chains hydrogen bond to the surface of the protein through their terminal sugars, but otherwise do not interact strongly with the enzyme. The structures have ten serine/threonine residues, to each of which is linked a single mannose sugar. The structure of the ten O-glycosylated residues taken together suggests a well-defined conformation for proteins that have extensive O-glycosylation of their polypeptide chain.

Aspergillus↗

1,N2-cyclic deoxyguanosine adducts and guanine adducts of 2-haloacroleins. Isolation, characterization, isomerization and stability.

The reaction of the mutagenic 2-haloacroleins, 2-fluoroacrolein, -2-chloroacrolein and 2-bromoacrolein, with nucleosides and 5'-mononucleotides was studied. We found two different regioisomers of 1,N2-cyclic deoxyguanosine adducts of 2-chloroacrolein and 2-bromoacrolein: type A, the 6-hydroxy, 7-haloadduct in which the OH-substituent is vicinal to the N2-atom of the guanine moiety and type B, the 8-hydroxy, 7-haloadduct in which the OH-group is adjacent to the N1-atom of the guanine moiety. The major adducts were the trans pairs of diastereomers of type A and type B in which the 6,7-substituents as well as the 7,8-substituents are in the energetically favoured diaxial position of the newly formed tetrahydropyrimidine ring. In the case of the type A regioisomers, the cis pairs of diastereomers (traces with chloroacrolein and about 4% with bromoacrolein) were also found in which the halosubstituent probably takes the equatorial position. Due to the anomeric effect, the OH-group takes the axial position in both regioisomers. No cis isomers of the type B regioisomers could be isolated. Acid hydrolysis of the deoxyguanosine adducts released deoxyribose, and the respective guanine adducts were isolated and characterized. Besides the vicinal halo, hydroxy adducts, trace amounts of the corresponding dihydroxy adducts were formed by hydrolysis of the chlorine or bromine substituents. The dihydroxy compounds possess the same structures and conformations in the newly formed tetrahydropyrimidine ring as do the halo, hydroxy adducts. Under our conditions no adducts other than those with deoxyguanosine and guanine could be identified.(ABSTRACT TRUNCATED AT 250 WORDS)

Acrolein↗

Diminished brain glucose metabolism is a significant determinant for falling rates of systemic glucose utilization during sleep in normal humans.

Systemic glucose utilization declines during sleep in man. We tested the hypothesis that this decline in utilization is largely accounted for by reduced brain glucose metabolism. 10 normal subjects underwent internal jugular and radial artery cannulation to determine cerebral blood flow by N2O equilibrium technique and to quantitate cross-brain glucose and oxygen differences before and every 3 h during sleep. Sleep stage was graded by continuous electroencephalogram, and systemic glucose turnover was estimated by isotope dilution. Brain glucose metabolism fell from 33.6 +/- 2.2 mumol/100 g per min (mean +/- SE) before sleep (2300 h) to a mean nadir of 24.3 +/- 1.1 mumol/100 g per min at 0300 h during sleep (P = 0.001). Corresponding rates of systemic glucose utilization fell from 13.2 +/- 0.8 to 11.0 +/- 0.5 mumol/kg per min (P = 0.003). Diminished brain glucose metabolism was the product of a reduced arteriovenous glucose difference, 0.643 +/- 0.024 to 0.546 +/- 0.020 mmol/liter (P = 0.002), and cerebral blood flow, 50.3 +/- 2.8 to 44.6 +/- 1.4 cc/100 g per min (P = 0.021). Brain oxygen metabolism fell commensurately from 153.4 +/- 11.8 to 128.0 +/- 8.4 mumol/100 g per min (P = 0.045). The observed reduction in brain metabolism occurred independent of stage of central nervous system electrical activity (electroencephalographic data), and was more closely linked to duration of sleep. We conclude that a decline in brain glucose metabolism is a significant determinant of falling rates of systemic glucose utilization during sleep.

Activity Cycles↗

Medicaid payment for nonphysician practitioners: an access issue.

As part of congressional efforts in the 1980s to expand access to care for Medicaid mothers and children, states were required to pay for services provided by certain advanced practice nurses. These mandates created the impetus in many states to expand payment policies for nonphysician practitioners. State Medicaid payment policies are often less restrictive than those of the Medicare program. However, not all states have been receptive to policy expansions and do not cover nonphysician practitioner services to the extent that professional practice acts allow. A few states have yet to meet the 1989 federal mandates.

Health Services Accessibility↗

The possible role of alpha, beta-unsaturated carbonyl compounds in mutagenesis and carcinogenesis.

alpha, beta-Unsaturated carbonyl compounds are industrially important compounds, ubiquitous in the environment and are formed endogenously. They interact with proteins and enzymes. Genotoxicity was found in eucaryotic cells and some compounds were carcinogenic. Unsaturated carbonyl compounds are considered to play an important role in human cancer. Insufficient and contradictory results were reported on mutagenicity. We demonstrated a clear mutagenic potential for these compounds and have shown interference of their bacterial toxicity with an adequate testing. Structure-mutagenicity relationships were confirmed by the results of the SOS-chromotest. The compounds induce DNA-strand breaks. However, we did not find indications for cross linking. With mutagenic alpha, beta-unsaturated carbonyl compounds we isolated and characterized 1,N2-cyclic deoxyguanosine adducts, 7,8-cyclic and 7-linear guanine adducts as well as 1,N2-7,8-biscyclic adducts and 1,N2-cyclic, 7-linear bisadducts. Reactivity of these compounds towards nucleosides runs in parallel with their mutagenic potential. Mutagenic and carcinogenic activities most probably depend on these reactions with DNA, and DNA adducts can be utilized as indicators for the role of these compounds in human carcinogenicity.

Aldehydes↗

Vesicoureteral reflux and lower urinary tract injury: the possible role of suprapubic cystostomy.

Incidental vesicoureteral reflux was noted frequently during routine cystographic evaluation of patients who suffered vesicourethral trauma and who were managed by suprapubic cystostomy. Based on this observation we designed a retrospective study to document the prevalence of vesicoureteral reflux among 30 consecutive patients following vesicourethral trauma. In 9 patients drainage was instituted by urethral catheter and in 21 by suprapubic cystostomy. Of the latter 21 patients 10 (47.6%) had evidence of vesicoureteral reflux on cystography, which was associated with complete rupture of the urethra in 9 (90%). No patient who was treated initially with a urethral catheter had evidence of vesicoureteral reflux on cystography. We conclude that the prevalence of vesicoureteral reflux is significantly affected by the coexistence of severe vesicourethral injury and the presence of suprapubic cystostomy. The significance of this observation is in the potential risk of ascending upper urinary tract infections due to the hazardous combination of vesicoureteral reflux and frequent recurrent lower urinary tract infections. Presence of vesicoureteral reflux in these patients may necessitate a prophylactic antibiotic regimen. The specific mechanisms that lead to increased prevalence of vesicoureteral reflux in patients following severe vesicourethral injury are not defined by our results. However, we propose a multifactorial concept that may explain our observation.

Adult↗

Biomonitoring studies and susceptibility markers for acrolein congeners and allylic and benzyl compounds.

The importance of genotoxic acrolein congeners and allylic and benzyl compounds as industrial compounds, ubiquitous environmental pollutants, and naturally occurring substances necessitates the availability of adequate biomonitoring techniques. Endogenously formed acrolein congeners are considered to play an important role in carcinogenesis. Our studies have demonstrated that acrolein congeners react with DNA components and form adducts with the guanine moiety. We have identified and characterized cyclic 1,N2-deoxyguanosine adducts, cyclic 7,8-guanine adducts, linear 7-guanine adducts, 1,N2,7,8-bis-cyclic adducts, and 1,N2-cyclic, 7-linear bis adducts. Both the reactivity of the acroleins toward nucleosides and their mutagenicity in S. typhimurium TA100 decrease with increasing degree of alkyl substitution. Adducts are now available as reference substances for developing sensitive detection methods. Of the biomonitoring methods investigated for allylic and benzyl compounds, the detection of cysteine and histidine adducts isolated from hemoglobin seems to be the most sensitive. Gas chromatography with electron capture detection of heptafluorobutyric acid derivatives allows a detection limit in the femtomole range, HPLC-fluorescence detection of O-phthalic dialdehyde derivatives allows a limit in the picomole range, and detection of 9-fluorenylmethyl-chlorofomiate derivatives allows a limit in the femtomole range.

Acrolein↗

Differential effects of daughters' marital status on their parent care experiences.

This study compared the parent care experiences of five groups of daughters (N = 492) (married, remarried, separated/divorced, widowed, and never married). Data include demographic characteristics and measures of depression, positive affect, personality strength, health, social support, relationship quality, caregiving burden, caregiving mastery, and caregiving satisfaction. Women with husbands had more socio-emotional and instrumental support, much higher incomes, less financial strain from caregiving, and less depression. They felt their own particular marital status made caregiving easier than did the three groups of not-married women.

Adult↗

Measurement of free radicals from smoke inhalation and oxygen exposure by spin trapping and ESR spectroscopy.

Research in smoke inhalation has established that free radicals are produced from gases released during combustion and these species impair lung function. Using spin traps and their adducts in an animal model free radicals were measured. Various hyperbaric oxygen regimens were tested in an attempt to attenuate pulmonary damage caused by free radical reactions. Our data demonstrated that persistent oxygen- and carbon-centered free radicals are detectable in intravascular fluids after smoke inhalation. The smoke inhalation model showed however, clearing of spin trap adducts one hour after smoke exposure. Other researchers have found that when 100% oxygen is given at 1 atmosphere absolute (ATA) for 1 h, free radicals were not detectable. However, oxygen given at 2.5 ATA does produce detectable free radicals. With continued exposure at this pressure, the levels of free radicals increase for up to 60 min. This study suggests that the level of free radical induced oxygen toxicity may be a function of oxygen pressure and duration of oxygen exposure.

Animals↗

Effect of transport time and FiO2 on SpO2 during transport from the OR to the PACU.

Early postoperative hypoxemia may be due to a reduced functional residual capacity, hypoventilation, and ventilation-perfusion mismatch. These factors reduce the partial pressure of the arterial oxygen which ultimately reduces the oxygen transported to the tissues by decreasing the hemoglobin saturation. This may lead to cellular ischemia and death. Oxygen saturation may decrease during transport from the operating room to the postanesthesia care unit. The length of transport time in large operating suites may exceed 5 minutes, which may lead to inadequate oxygenation. This research used a pretest-posttest control group design on a convenience sample. Subjects were randomized into either the treatment or control group. At emergence, the SpO2 measured and the stopwatch started. The treatment group received 40% oxygen via a venturi mask during transport while the control group breathed room air. After a routine transport to the postanesthesia care unit, the SpO2 was again measured and the transport time was recorded. Oxygen saturation was found to be significantly greater in the group breathing supplemental O2 during transport.

Adult↗

Mutagenicity and genotoxicity of ethylvinyl ketone in bacterial tests.

The mutagenic and genotoxic effects of ethylvinyl ketone were investigated. This alpha, beta-unsaturated carbonyl compound is widely distributed in the environment, in particular in food. Whereas ethylvinyl ketone shows only weak genotoxicity in the SOS Chromotest with Escherichia coli PQ37, it was distinctly mutagenic per se in the Salmonella preincubation assay with TA100. Using SKF 525 (an inhibitor of microsomal monooxygenase) and trichloropropene oxide (an inhibitor of epoxide hydrolase) we found indication for additional activation via epoxidation by S9 mix. The need for further investigation of the genotoxic, mutagenic and carcinogenic effects of this compound is strongly indicated.

Animals↗

Comparative bacterial clearances of muscle and skin/subcutaneous tissues with and without dead bone: a laboratory study.

Seventeen New Zealand White rabbits underwent implantation of three different concentrations of bacteria and a sterile saline control solution with and without dead autologous bone in eight separate muscular and eight separate subcutaneous sites. Following a period of 1 week, each site was surgically explored and samples of tissue were taken for histology and quantitative culture. Results reveal that final bacterial concentrations in the subcutaneous sites were significantly lower than in the muscle sites (p less than or equal to 0.0001) for each concentration of bacteria, with and without dead bone. Dead bone resulted in very significantly greater bacterial concentrations in both subcutaneous and muscle sites. Clinically, these results indicate that a thorough bony wound debridement is more important than the type of tissue used to close the wound. Flap tissue should be selected with regard to the perfusion, contour, and appearance of the recipient site.

Abscess↗

Molecular mechanisms of DNA damage initiated by alpha, beta-unsaturated carbonyl compounds as criteria for genotoxicity and mutagenicity.

alpha, beta-Unsaturated carbonyl compounds are important not only from a theoretical but also a practical standpoint. These ubiquitous compounds can interact with DNA through various mechanisms. The predominant interaction is the formation of cyclic 1,N2-deoxyguanosine adducts; 7,8-cyclic guanine adducts are also found. We have synthesized and characterized the stereoisomers of adducts formed by about 20 alpha, beta-unsaturated carbonyl compounds. The different types of adducts and the mutagenic and genotoxic response can be explained by the molecular structures of the agents. Compounds forming saturated cyclic adducts are mutagenic in S. typhimurium strain TA100 and to a lesser extent in TA1535. Substances with a leaving group at the C-3 position form unsaturated conjugated cyclic adducts and are mutagenic only in the His D3052 frameshift strains with an intact excision repair system (no urvA mutation). Metabolic epoxidation of the double bond and other metabolic activation, e.g., activation of the nitrogroups via nitroreductases, were also found to contribute to genotoxic and mutagenic activities. Our results have further elucidated the genotoxic mechanisms of these compounds; however, additional investigations are required for a complete understanding of the genotoxic activity of this class of compounds.

Acrolein↗

Medicaid versus state funding of community residences: impact on daily life of people with mental retardation.

The unintended effects on quality of life that flow from decisions regarding funding sources used to support community-based residential programs were documented. Results show that community residence program structures play an important role in determining quality of life after deinstitutionalization. Clients living under program structures flowing from the Medicaid ICF/MR funding source were less active and involved in life than were clients living in programs funded by non-Medicaid state sources. We hypothesized that the reason for this differential outcome was the result of Medicaid funding regulations and their interpretation, which create an institutional-like set of program structures leading to restrictive care patterns.

Activities of Daily Living↗