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Biomedical subjects

R B White

Publications and source records attributed to R B White.

At least 37 records · Page 2Linked to original sources
PubMed1997

Human liver CYP2B6-catalyzed hydroxylation of RP 73401.

RP 73401 is a potent inhibitor of cyclic nucleotide phosphodiesterase type IV. RP 73401 is metabolized by human liver microsomes almost exclusively by transhydroxylation of the cyclopentyl group to RPR 113406. Liquid chromatography/mass spectrometry/mass spectrometry analysis of plasma from patients given RP 73401 also revealed a molecular ion and fragmentation consistent with RPR 113406. Thus, the objective was to determine the oxidative enzyme(s) responsible for RP 73401 hydroxylation. Kinetic constants of RP 113406 formation ranged from 8 to 26 MM and 0.83 to 5.99 nmol/min/mg protein for K(m) and V(max), respectively (n = 3). Enzyme activity varied 23-fold among 15 human liver microsome samples and correlated with CYP2A6-catalyzed coumarin hydroxylase (r2 = 0.85, P < .01) and CYP2B6-catalyzed 7-ethoxytrifluoromethylcoumarin O-deethylase (r2 = 0.82, P < .01) activities. Chemical inhibition studies showed a 63% decrease in RP 73401 hydroxylation by 500 microM orphenadrine. Coumarin (10 microM), however, did not inhibit RP 73401 hydroxylation. Also, anti-CYP2B1 IgG produced 85% inhibition of RP 73401 hydroxylation, but only a negligible decline in coumarin hydroxylase activity. Of the 10 expressed P450 forms studied, only CYP2B6 catalyzed RP 73401 hydroxylation. Finally, expressed CYP2B6 showed a high affinity (K(m) = 22.5 microM) for RP 73401 hydroxylation, similar to the human liver microsome studies.

Aryl Hydrocarbon Hydroxylases↗
PubMed1996

Epoetin alfa--focus on nursing case management. Case study of the anemic patient.

Case management is a multidisciplinary collaborative approach that emphasizes continuity of patient care. Nursing case management can lead to improvements in the quality of care while affording nurses the opportunity to increase their expertise, autonomy, and authority in the health care system. Treatment of the anemia of end-stage renal disease (ESRD) is used as an example to illustrate the implementation of these principles in the dialysis unit.

Anemia, Iron-Deficiency↗
PubMed1996

Catalytic role of cytochrome P4502B6 in the N-demethylation of S-mephenytoin.

In vitro methods were used to identify the cytochrome P450 (CYP) enzyme(s) involved in S-mephenytoin N-demethylation. S-Mephenytoin (200 microM) was incubated with human liver microsomes, and nirvanol formation was quantitated by reversed-phase HPLC. S-Mephenytoin N-demethylase activity in a panel of human liver microsomes ranged 35-fold from 9 to 319 pmol/min/mg protein and correlated strongly with microsomal CYP2B6 activity (r = 0.91). Additional correlations were found with microsomal CYP2A6 and CYP3A4 activity (r = 0.88 and 0.74, respectively). Microsomes prepared from human beta-lymphoblastoid cells transformed with individual P450 cDNAs were assayed for S-mephenytoin N-demethylase activity. Of 11 P450 isoforms (P450s 1A1, 1A2, 2A6, 2B6, 2E1, 2D6, 2C8, 2C9, 2C19, 3A4, and 3A5) tested, only CYP2B6 catalyzed the N-demethylation of S-mephenytoin with an apparent K(m) of 564 microM. Experiments with P450 form-selective chemical inhibitors, competitive substrates, and anti-P450 antibodies were also performed. Troleandomycin, a mechanism-based CYP3A selective inhibitor, and coumarin, a substrate for CYP2A6 and therefore a potential competitive inhibitor, failed to inhibit human liver microsomal S-mephenytoin N-demethylation. In contrast, orphenadrine, an inhibitor of CYP2B forms, produced a 51 +/- 4% decrease in S-mephenytoin N-demethylase activity in human liver microsomes and a 45% decrease in recombinant microsomes expressing CYP2B6. Also, both CYP2B6-marker 7-ethoxytrifluoromethylcoumarin O-deethylase and S-mephenytoin N-demethylase activities were inhibited by approximately 65% by 5 mg anti-CYP2B1 IgG/mg microsomal protein. Finally, polyclonal antibody inhibitory to CYP3A1 failed to inhibit S-mephenytoin N-demethylase activity. Taken together, these studies indicate that the N-demethylation of S-mephenytoin by human liver microsomes is catalyzed primarily by CYP2B6.

Antibodies, Monoclonal↗
PubMed1992

Adrenal-kidney and gonadal steroidogenesis during sexual differentiation of a reptile with temperature-dependent sex determination.

Adrenal-kidney and gonadal steroidogenesis were studied during early development in the red-eared slider turtle, Trachemys scripta, which exhibits temperature-dependent sex determination. In vitro steroid secretion by adrenal-kidney-gonad complexes (AKGs) incubated for 6 hr was determined by radioimmunoassay (RIA). AKGs from presumptive males and females secreted progesterone at developmental stages before (stage 15), during (stages 17 and 19), and after (stage 21) the temperature-sensitive period for sex determination, and progesterone secretion increased significantly throughout the period from stage 15 to 21. Presumptive male AKGs secreted significantly more progesterone than female AKGs at stage 19. Corticosterone secretion by AKGs was observed at stage 17 in males only, but in both sexes at stages 19 and 21. Testosterone, estradiol, androstenedione, and dehydroepiandrosterone secretion by AKGs was detected only at stage 21. Of the steroids measured, progesterone and corticosterone were consistently secreted at the highest levels. Although some sex differences were observed, no obvious patterns of sexually dimorphic steroid secretion from AKGs were apparent. Gonads from stage 21, stage 24, and 10-day-old hatchlings from both presumptive sexes incubated with [7-3H]pregnenolone showed only weak precursor conversion, primarily to polar metabolites, in incubations as long as 24 hr. None of the steroids assessed by RIA of AKG incubates could be identified by TLC or HPLC analysis of the stage 21 and stage 24 gonadal incubates. However, progesterone was tentatively identified in incubates of 10-day post-hatch female gonads. For stage 21 females, AKGs were separated into gonadal and adrenal-kidney tissue (AK) components and incubated in vitro for 1, 3, and 18 hr.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Glands↗
PubMed1992

Current parental stress in maltreating and nonmaltreating families of children with multiple disabilities.

Questionnaires were mailed to families of children with multiple disabilities to investigate whether differences in parental perception of stress and burden of care could be identified in those families who had previously been reported and substantiated as abusive or neglectful as compared to those families who had not been so reported. Two hundred and fifty-seven parents completed Friedrich's revised version of Holroyd's Questionnaire on Resources and Stress (QRS-F), an instrument designed to measure stress and burden of care in families of children with disabilities. Twenty-five (9.7%) had previously substantiated maltreatment reports. Results suggest that a history of maltreatment is not related to the family's currently perceived stress levels as measured by the Friedrich scale. Implications of the results are discussed.

Adolescent↗
PubMed1992

Stimulation of in vitro steroidogenesis by pituitary hormones in a turtle (Trachemys scripta) within the temperature-sensitive period for sex determination.

To investigate the possible involvement of pituitary hormones in the regulation of steroidogenesis during reptilian sexual differentiation, we tested the ability of gonadotropin (ovine FSH), adrenocorticotropin (porcine ACTH), and growth hormone (bovine GH) to stimulate in vitro steroidogenesis in embryonic adrenal-kidney-gonad complexes (AKGs) of a turtle, Trachemys scripta, during and after the temperature-sensitive period for sex determination (TSP). Radioimmunoassays were used to measure progesterone, testosterone, estradiol, and corticosterone in incubation media; additionally, immunoreactive ACTH was measured in plasma. Presumptive male and female AKGs were stimulated by both FSH and ACTH at each stage investigated. Secretion of progesterone and corticosterone was usually far greater than that of testosterone or estradiol in both basal and hormone-stimulated incubations. In general, AKGs from presumptive males secreted more progesterone and corticosterone than AKGs from presumptive females. Progesterone and estradiol secretions were stimulated by both FSH and ACTH, but testosterone secretion was stimulated only by ACTH. Corticosterone secretion was strongly stimulated by ACTH. GH failed to significantly stimulate steroid secretion. Plasma ACTH levels were significantly higher in males than in females, and both sexes had significantly higher plasma levels of ACTH after the TSP compared to during the TSP. Our data demonstrate that during the temperature-sensitive period AKGs are responsive to both gonadotropin and ACTH, and that there are significant sex differences in steroidogenesis, sensitivity to gonadotropin and ACTH, and plasma ACTH levels.

Adrenocorticotropic Hormone↗
PubMed1991

Targeted enzyme therapy of experimental glomerulonephritis in rats.

We sought to determine whether systemic administration of proteases ameliorates membranous nephritis induced in rats by immunization and challenge with cationic bovine gamma globulin, and whether targeting of protease to glomerular capillaries increases efficacy. Proteases substituted with biotin were targeted via the cationic protein avidin A, which by virtue of its charge has affinity for the glomerular basement membrane. Despite identical pretreatment proteinuria, rats given untargeted protease (biotin-conjugated without avidin, or unconjugated plus avidin) had significantly less proteinuria than saline-treated controls and nephrotic rats given avidin plus biotin-conjugated (targeted) protease had even less proteinuria and reduced glomerular rat IgG and C3. Among more severely nephrotic rats, targeted protease was again more effective than untargeted protease at reducing proteinuria, and also decreased the size of electron-dense glomerular deposits, hypercholesterolemia, and creatininemia. Inactivated targeted proteases had no effect on proteinuria, hypercholesterolemia, or azotemia. Finally, active targeted protease did not affect proteinuria in the nonimmune mediated nephrosis induced by puromycin aminonucleoside. We conclude that systemic protease can specifically diminish glomerular immune deposits, proteinuria, hyperlipidemia, and creatininemia associated with experimental immune complex glomerulonephritis but not toxic nephrosis, and that targeted protease is more effective than untargeted protease.

Albuminuria↗
PubMed1990

Reported maltreatment in children with multiple disabilities.

This study examined a population of children with multiple disabilities to investigate whether functional, developmental, or perinatal factors could differentiate children reported and substantiated as maltreated from those not so reported. Data were collected from medical records of a cohort of 500 children evaluated between 1973 and 1984 at the Kennedy Institute in Baltimore, Maryland. Maltreatment reporting was documented through the State of Maryland Abuse Registry and the counties of residence of all study children. Results indicated that the profiles of demographic and family characteristics associated with child maltreatment reporting in this population are consistent with the literature, but child functional and developmental characteristics were not confirmed as risk factors for substantiated maltreatment reports. Indeed, contrary to investigator expectations, the more severely disabled children, in terms of functioning, appeared at less risk of maltreatment than did disabled children functioning at more age-appropriate levels.

Activities of Daily Living↗
PubMed1985

Maternal perinatal risk factors and child abuse.

A retrospective matched pair study was designed to compare maternal perinatal factors such as abnormal pregnancy history and labor and delivery experience in families who subsequently were reported as physically abusive to one or more of their children as compared to non-abusive families. The study population consisted of the mothers of 532 children reported to the Baltimore (Maryland) Department of Social Services as physically abused during the years 1975-77. The comparison group was handmatched to the study group from State of Maryland birth certificates on the basis of the abused child's birth year and sex, maternal race, education and hospital of delivery. The study population was 67% black with a mean maternal education of 10.5 completed years. The abused children were 59% male with 48% less than 2 years of age. Results indicated that selected medical definitions of abnormal pregnancy, labor and delivery did not identify families at differential risk of maltreatment. However, mothers in maltreating families were younger, had shorter birth intervals, less prenatal care and were significantly more likely to have had a stillbirth or reported abortion or a prior child death. Study limitations are addressed as are suggestions for future research.

Adolescent↗
PubMed1985

Selected perinatal factors and child abuse.

A matched pair case-control study was conducted to compare birth weights, gestations, and length of hospital stay (LOS) of 532 children subsequently reported as physically abused with comparable data from a group of control children matched on age, sex, race, and maternal education. Our results indicated a moderate association between both low birthweight and very short gestation with physical abuse. Results for LOS were inconclusive.

Adolescent↗
PubMed1982

Family size composition differentials between central city-suburb and metropolitan-nonmetropolitan migration streams.

During the migration intervals 1965-19709, 1970-1975, and 1975-1979, families that migrated from Standard Metropolitan Statistical Areas (SMSAs) to nonmetropolitan areas and from central cities to suburban rings were larger in mean size than families that composed the respective counterstreams. Mean family sizes declined sharply for all groups throughout the period, but absolute differentials between opposing streams increased slightly. In terms of the selective attraction of families by size, nonmetropolitan net in-migration was very similar to suburbanization within SMSAs. A considerable portion of recent nonmetropolitan net gains resulted from the exchange of larger in-migrant families for smaller out-migrant families.

Demography↗
PubMed1981

Services for children with congenital facial clefts through a state Crippled Children's Service Program.

A study to analyze the involvement of the Maryland State Crippled Children's Services (CCS) with children with congenital facial clefts was conducted in two parts. The first phase identifies all children born to Maryland residents over a three-year period to measure the incidence by type of the cleft condition. Phase two examines CCS involvement for 816 children with congenital facial clefts, including 114 of the Phase 1 cohort group. Diagnostic and demographic data are analyzed with specific attention to services involved in the child's entry into, flow through, and discharge from the CCS program. The 816 study cases known to the Maryland CCS Program during the period of study were characterized by the presence and type of parental congenital malformations, reasons for termination of CCS services, number of professional encounters, age at entry, distances to CCS care providers, demographic characteristics, and hospitalization history. Data analysis suggests that the age at which a child first becomes known to the CCS Program is significantly associated with areas of residence, presence of other malformations, type of cleft, and presence of other malformations in the family. The data further suggest that CCS Programs reassess their capacity to develop administratively useful data for use in program planning, evaluation, and research. The present systems appear to require further alteration for updating and expansion to increase the availability of useful, timely, and accurate programmatic data.

Adolescent↗
PubMed1979

Relationship of scores on the Escapism Scale of the MMPI to escape from minimum security federal custody.

Investigated the ability of the Escapism (Ec) scale of the MMPI to differentiate between escape and non-escape minimum security federal prisoners. At the .05 level there was no difference between the scores of the two groups on the Ec scale or on comparisons of other correctional data, age, and ethnic composition. It appears that the Ec scale alone or in combination with other data will be a poor predictor of escape. Also, the rate of escape was so low as to make accurate prediction from any criteria extremely unlikely.

Adult↗