Search PubMed⌕ Search

Biomedical subjects

R A Kramer

Publications and source records attributed to R A Kramer.

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

Psychosocial characteristics of physically abused children and adolescents.

OBJECTIVE: To examine the association between physical abuse and selected psychosocial measures in a community-based probability sample of children and adolescents. METHOD: A sample of 9- through 17-year-olds (N = 665) and their caretakers in New York State and Puerto Rico were interviewed in the Methods for the Epidemiology of Child and Adolescent Mental Disorders (MECA) Study. Assessments included the Columbia Impairment Scale, the Instrumental and Social Competence Scale, the Diagnostic Interview Schedule for Children, the Peabody Picture Vocabulary Test, and questions regarding physical abuse. Regression analyses were conducted controlling for family income, family psychiatric history, perinatal problems, physical health, and sexual abuse. RESULTS: A history of physical abuse was reported in 172 (25.9%) of the sample. It was significantly associated with global impairment, poor social competence, major depression, conduct disorder, oppositional defiant disorder, agoraphobia, overanxious disorder, and generalized anxiety disorder but not with suicidality, school grades, or receptive language ability. CONCLUSION: A community probability sample of children and adolescents demonstrated significant associations between physical abuse and psychopathology, after controlling for potential confounders. This supports comprehensive screening for psychopathology among physically abused children and for physical abuse among those with psychopathology. Interventions aimed at improving social competence may be indicated.

Adolescent↗
PubMed1995

Mouse macrophage metalloelastase expressed in bacteria absolutely requires zinc for activity.

Mouse macrophage metalloelastase was expressed in Escherichia coli. This recombinant enzyme (rMME) was present in the inclusion bodies that were solubilized in 7 M guanidine HCl. After removal of guanidine HCl, rMME was purified with a Q-Sepharose column. Degradation of [3H]elastin by rMME absolutely required Ca2+; the optimal Ca2+ concentration was 5 mM. NaCl stimulated the enzyme activity; maximal stimulation was obtained at 400 mM. The rMME activity was inhibited by metalloprotease inhibitors, but not by serine, aspartyl, or thiol protease inhibitors. Among the divalent cations tested, only Ba2+ and Sr2+ exhibited marginal stimulation of rMME activity in the absence of Ca2+. Cu2+, Zn2+, or Cd2+ strongly inhibited rMME activity with IC50 values between 68 and 180 microM, while Mg2+, Ba2+, Mn2+, Co2+, and Sr2+ had no effect. The requirement of Zn2+ for rMME activity was determined. Significant enzyme activity was present in rMME treated with EDTA followed by Q-Sepharose column chromatography. Only when the inclusion bodies were solubilized in the presence of 20 mM EDTA, did an enzyme preparation which was absolutely dependent on exogenous Zn2+ for activity result. The optimal Zn2+ concentration for rMME activation was 100 microM. These results indicate that Zn2+ is tightly bound to rMME.

Amino Acid Sequence↗
PubMed1995

Health and social characteristics and children's cognitive functioning: results from a national cohort.

OBJECTIVES: The purpose of this study was to examine the associations between cognitive functioning in children and sociodemographic, family, and health characteristics. METHODS: Data from phase 1 of the third National Health and Nutrition Examination Survey were used to evaluate performance on standardized cognitive tests in a representative sample of 2531 children 6 to 16 years of age. Multivariate analyses were used to assess independent associations between covariates and test performance. RESULTS: Lower income, minority status, and lower education of an adult reference person (one of the persons in the household who owned or rented the home) were independently associated with poorer performance on all cognitive subtests. To a lesser degree, general health status, history of birth complications, and sex also were independent predictors of performance for some of the subtests. CONCLUSIONS: These findings illustrate disparities in cognitive functioning across sociodemographic and health characteristics of children in the US population. They suggest the need for public health policies to take a multifaceted approach to optimizing childhood environments in order to overcome the effects of socioeconomic and minority status.

Adolescent↗
PubMed1994

Blood lead levels in the US population. Phase 1 of the Third National Health and Nutrition Examination Survey (NHANES III, 1988 to 1991)

OBJECTIVE: To determine mean blood lead levels and their sociodemographic correlates in the US population. DESIGN: Nationally representative cross-sectional health examination survey that included measurements of venous blood lead. PARTICIPANTS: A total of 13,201 persons aged 1 year and older examined during phase 1 of the third National Health and Nutrition Examination Survey (1988 to 1991). RESULTS: The overall mean blood lead level for the US population was 0.14 mumol/L (2.8 micrograms/dL). Blood lead levels were consistently higher for younger children than for older children, for older adults than for younger adults, for males than for females, for blacks than for whites, and for central-city residents than for non-central-city residents. Other correlates of higher blood lead levels included low income, low educational attainment, and residence in the Northeast region of the United States. National estimates for children 1 to 5 years of age indicate that 8.9%, or approximately 1.7 million children, have blood lead levels 0.48 mumol/L (10 micrograms/dL) or greater. These levels are high enough to be of health concern under 1991 Centers for Disease Control and Prevention guidelines. CONCLUSIONS: The low overall mean blood lead levels demonstrate a major public health success in primary prevention efforts. However, exposure to lead at levels that may adversely affect the health of children remains a problem especially for those who are minority, urban, and from low-income families. Strategies to identify the most vulnerable risk groups are necessary to further reduce lead exposure in the United States.

Adolescent↗
PubMed1994

The decline in blood lead levels in the United States. The National Health and Nutrition Examination Surveys (NHANES)

OBJECTIVE: To describe trends in blood lead levels for the US population and selected population subgroups during the time period between 1976 and 1991. DESIGN: Two nationally representative cross-sectional surveys and one cross-sectional survey representing Mexican Americans in the southwestern United States. SETTING/PARTICIPANTS: Participants in two national surveys that included blood lead measurements: the second National Health and Nutrition Examination Survey, 1976 to 1980 (n = 9832), and phase 1 of the third National Health and Nutrition Examination Survey, 1988 to 1991 (n = 12,119). Also, Mexican Americans participating in the Hispanic Health and Nutrition Examination Survey, 1982 to 1984 (n = 5682). RESULTS: The mean blood lead level of persons aged 1 to 74 years dropped 78%, from 0.62 to 0.14 mumol/L (12.8 to 2.8 micrograms/dL). Mean blood lead levels of children aged 1 to 5 years declined 77% (0.66 to 0.15 mumol/L [13.7 to 3.2 micrograms/dL]) for non-Hispanic white children and 72% (0.97 to 0.27 mumol/L [20.2 to 5.6 micrograms/dL]) for non-Hispanic black children. The prevalence of blood lead levels 0.48 mumol/L (10 micrograms/dL) or greater for children aged 1 to 5 years declined from 85.0% to 5.5% for non-Hispanic white children and from 97.7% to 20.6% for non-Hispanic black children. Similar declines were found in population subgroups defined by age, sex, race/ethnicity, income level, and urban status. Mexican Americans also showed similar declines in blood lead levels of a slightly smaller magnitude over a shorter time. CONCLUSIONS: The results demonstrate a substantial decline in blood lead levels of the entire US population and within selected subgroups of the population. The major cause of the observed decline in blood lead levels is most likely the removal of 99.8% of lead from gasoline and the removal of lead from soldered cans. Although these data indicate major progress in reducing lead exposure, they also show that the same sociodemographic factors continue to be associated with higher blood lead levels, including younger age, male sex, non-Hispanic black race/ethnicity, and low income level. Future efforts to remove other lead sources (eg, paint, dust, and soil) are needed but will be more difficult than removing lead from gasoline and soldered cans.

Adolescent↗
PubMed1993

Functional imaging of multidrug-resistant P-glycoprotein with an organotechnetium complex.

The multidrug-resistant P-glycoprotein (Pgp), a M(r) 170,000 plasma membrane protein encoded by the mammalian multidrug resistance gene (MDR1), appears to function as an energy-dependent efflux pump. Many of the drugs that interact with Pgp are lipophilic and cationic at physiological pH. We tested the hypothesis that the synthetic gamma-emitting organotechnetium complex, hexakis(2-methoxyisobutylisonitrile)technetium(I) ([99mTc]SESTAMIBI), a lipophilic cationic radiopharmaceutical, could be a suitable Pgp transport substrate capable of functional imaging of the MDR phenotype. The cellular pharmacological profile of [99mTc]SESTAMIBI transport was examined in Chinese hamster V79 lung fibroblasts and the 77A and LZ derivative cell lines which express modestly low, intermediate, and very high levels of Pgp, respectively. Steady-state contents of [99mTc]SESTAMIBI in V79, 77A, and LZ cells were 10.0 +/- 0.5 (SEM) (n = 9), 3.6 +/- 0.5 (n = 8), and 0.4 +/- 0.02 (n = 9) fmol.(mg protein)-1 (nMo)-1, respectively, consistent with enhanced extrusion of the imaging agent by Pgp-enriched cells. Maximal doses (> 100 microM) of the multidrug-resistant reversal agents verapamil and cyclosporin A enhanced [99mTc]SESTAMIBI accumulation in V79, 77A, and LZ cells by approximately 10-, 25-, and 200-fold, respectively. The median effective concentration values for tracer accumulation in the presence of verapamil in V79, 77A, and LZ cells were 4, 100, and 200 microM, and those for cyclosporin A were 0.9, 3, and > 25 microM, respectively. Pgp-mediated [99mTc]SESTAMIBI transport occurred against its electrochemical gradient and was found to be ATP dependent displaying an apparent Km of 50 microM. Carrier-added [99Tc]SESTAMIBI was 11- to 13-fold less toxic in multidrug-resistant cells, and inhibited photolabeling of Pgp by [125I]iodoaryl azidoprazosin in a concentration-dependent manner; half-maximal displacement was observed at approximately 100- to 1000-fold molar excess [99Tc]SESTAMIBI. Exploiting the favorable gamma emission properties of 99mTc, functional expression of Pgp was successfully imaged in human tumor xenographs in nude mice with pharmacologically inert tracer quantities of [99mTc]SESTAMIBI. Functional imaging with these organotechnetium complexes may provide a novel mechanism to rapidly characterize Pgp expression in human tumors in vivo, target reversal agents in vivo, and ultimately provide a means to direct patients to specific cancer therapies.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1993

Gravidity, blood pressure, and hypertension among white women in the Second National Health and Nutrition Examination Survey.

Gravidity and parity have been hypothesized as possible protective factors for hypertension in women, but results of previous studies have been conflicting; none of three U.S. studies has clearly demonstrated this relation. We studied the association of number of pregnancies to blood pressure and hypertension in a cross-sectional study of 4,626 white women, ages 20-74 years, examined in the Second National Health and Nutrition Examination Survey. In univariate analyses, neither mean systolic blood pressure, mean diastolic blood pressure, nor prevalence of hypertension varied systematically with the number of pregnancies. In multivariate analyses that included age, body size, smoking, oral contraceptive use, education, poverty status, and alcohol use, systolic blood pressure declined modestly with greater gravidity. The association of gravidity with systolic blood pressure was stronger for younger premenopausal women. The odds of hypertension also declined with each additional pregnancy as compared with no pregnancies: there was an odds ratio of 0.90 (95% confidence interval = 0.81-0.99) for premenopausal women and an odds ratio of 0.95 (95% confidence interval = 0.92-0.98) for postmenopausal women. These findings indicate a slight negative relation of number of pregnancies to both blood pressure and hypertension.

Adult↗
PubMed1993

Makaluvamines, marine natural products, are active anti-cancer agents and DNA topo II inhibitors.

The makaluvamines were isolated from a sponge of the genus Zyzzya by following bioactivity against the human colon carcinoma cell line, HCT 116. These compounds have considerable cytotoxic activity. The makaluvamines appear to be acting through inhibition of DNA topoisomerase II. The compounds show enhanced toxicity toward a topoisomerase II-cleavable complex-sensitive cell line, they inhibit topoisomerase II decatenation of kinetoplast DNA in vitro. Makaluvamine C was shown to produce protein-linked DNA double-strand breaks, and makaluvamine A produced DNA double-strand breaks by neutral filter elution in a dose-dependent fashion similar to 4'-(9-acridinylamino)methanesulfon-m-anisidide (m-AMSA). The makaluvamines also increased the life span of nude mice bearing solid tumors of human ovarian cancer cells.

Animals↗
PubMed1992

Distribution of etanidazole into human brain tumors: implications for treating high grade gliomas.

Etanidazole was developed as an oxygen-mimetic radiosensitizer less lipophilic than misonidazole. Sensitization depends on an adequate concentration of drug in the tumor at the time of irradiation. Therefore, due to the presence of the blood-brain barrier, brain tumors may theoretically be difficult to radiosensitize due to the hydrophilic characteristics of etanidazole. Based on previous reports of loss of BBB integrity in brain tumors, we investigated the ability of etanidazole to penetrate into malignant gliomas of patients receiving etanidazole as part of a Phase I continuous infusion protocol. The patients had completed previous external beam irradiation. Twenty-two patients were studied and their etanidazole plasma and biopsy data were compared to the 2-compartment model derived from a second group of 19 patients with bolus etanidazole. Etanidazole concentration in brain tumor biopsies varied widely and appeared to be clustered into a higher and a lower pharmacokinetic group having mean tumor to well-perfused second compartment ratios of 1 and 0.25, respectively. Both high and low etanidazole concentrations were evident in different biopsies obtained from the same patient. Correlations between histology and tissue concentrations suggested that the higher level correspond to malignant tissue. These data indicate that the blood brain barrier is disrupted to varying degrees by the brain tumor and/or prior irradiation and that etanidazole penetrates into brain tumors.

Brain Neoplasms↗
PubMed1992

Final report of the phase I trial of continuous infusion etanidazole (SR 2508): a Radiation Therapy Oncology Group study.

Seventy-eight patients have been treated on a Phase I trial using continuous infusion etanidazole while undergoing brachytherapy for locally advanced tumors. There were two sequential schemata, the first treated 63 patients with doses ranging from 8-23 g/m2 over 48 hr and the second treated 15 patients with doses ranging from 20-23 g/m2 over 96 hr. The tumor sites were: brain (n = 42), cervix (n = 22), and breast (n = 14). Patients received a loading dose of etanidazole of 2 g/m2 followed by a continuous infusion for a total of 48 or 96 hr while radioactive implants were in place. Of the 63 patients in the 48-hr study, 52 were entered at doses of less than or equal to 21 g/m2 and there were no definite neuropathies but two patients with the cramping/arthralgia syndrome. Of the 11 patients entered at 22-23 g/m2, 1 patient had symptoms of peripheral neuropathy (Grade II) and 6 had the cramping/arthralgia syndrome. This is a new syndrome, distinct from the peripheral neuropathy, characterized by transient alterations in sensations consisting of cramping, arthralgias, or tingling that resolved completely at intervals varying from a few hours to about 1 week post-treatment. The cramping/arthralgia syndrome limited dose escalation; therefore, the maximum tolerated dose over 48 hr was determined to be 20-21 g/m2. The 96-hr infusion was limited to patients with recurrent gliomas undergoing stereotactic implantation. To date, 15 patients have been treated with doses of 20-23 g/m2. No toxicity was encountered at doses less than or equal to 22 g/m2. At 23 g/m2, one patient developed Grade III neuropathy and three patients had mild cramping/arthralgia syndrome, for whom the drug was discontinued. Therefore, it appears the maximum tolerated dose at 96 hr will be approximately 23 g/m2, which is 10-15% higher than for the 48-hr infusion.

Brachytherapy↗
PubMed1992

Age of onset in childhood asthma: data from a national cohort.

There is controversy over the role of age of asthma onset in childhood asthma. Data collected on self-reported physician-diagnosed asthmatic children and young adults aged 6-24 years (N = 352), who participated in the second National Health and Nutritional Examination, 1976-80 (NHANES II), a national sample, were examined to see whether reported age at onset was associated with the future course of the asthma. Three definitions were used for early-onset asthma: asthma beginning before the second birthday, before the third birthday, and before the fourth birthday. Late-onset asthma was defined as asthma beginning on or after the second birthday, the third birthday, and the fourth birthday, respectively. Among 6-14 year olds, late-onset asthmatic subjects as compared with early-onset asthmatic subjects using the three definitions reported more allergic rhinitis OR = 3.79 (95% CI 1.53, 9.41), 3.06 (1.33, 7.07), 2.71 (1.18, 6.22), and were more likely to have at least one positive allergen skin test OR = 2.21 (95% CI 1.02, 4.79), 2.90 (1.29, 6.49), 3.41 (1.50, 7.75). Late-onset asthmatic subjects tended to report that their asthma was active, have more problems during the past 12 months with wheezing, and have lower values for predicted FVC and FEV1. No difference was found in reported chronic rhinitis, sinusitis, other allergies, problems within the last 12 months with cough attacks, or during the past 3 years a period of cough and phlegm lasting more than 3 weeks.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1991

Expression of growth hormone-releasing factor analog Leu27GRF(1-44)OH in Escherichia coli: purification and characterization of the expressed protein.

A recombinant plasmid has been constructed to direct the synthesis of Leu27GRF(1-44)OH in Escherichia coli as a fusion protein containing a hexa-His tail followed by amino acids 1-99 of interferon-gamma and a methionine residue at the N-terminal. The expression of the 18-kDa fusion protein (H6GAMGRF) was induced by isopropylthiogalactoside treatment and the protein accumulated as insoluble aggregates in inclusion bodies. The protein aggregates were solubilized in 6 M guanidine-HCl and purified directly by affinity chromatography on a Nichelate column. The growth hormone-releasing factor (GRF) moiety was released from the fusion protein by cyanogen bromide cleavage and purified to homogeneity by anion-exchange chromatography followed by reverse-phase chromatography. The identity of the GRF peak was determined by comparing its retention time with that of synthetic Leu27GRF(1-44)OH. The purified material was further characterized by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, N-terminal sequencing, and amino-acid analysis. The recombinant-derived product and the synthetic compound showed identical reactivities toward anti-GRF polyclonal antibodies and were essentially equipotent as determined by an in vitro biological assay for growth hormone-releasing activity.

Amino Acid Sequence↗
PubMed1990

Expression of the HTLV-I tax transactivator in yeast: correlation between phenotypic alterations and tax function in higher eukaryotes.

The transcriptional activator protein (Tax) from human T-cell leukemia virus type 1 was expressed in yeast using several different promoters in several strains: In all instances, expression of Tax resulted in very strong aggregation of the yeast cells. This phenotype appears to be identical by all criteria tested to the flocculation phenotype of the dominant mutation flo 1. Of most significance, mutations in Tax that affect transactivation of the IL-2R alpha regulatory sequences, but retain their ability to activate the viral long terminal repeat also fail to yield the aggregation phenotype. Based on these findings, expression of Tax in yeast may prove to be a simple primordial system for examining the regulatory mechanisms and cellular functions involved in regulation of gene expression.

Gene Products, tax↗
PubMed1990

Access to care for children and adolescents with disabilities.

A survey of Connecticut pediatricians indicated that 90% of the respondents intended to provide care to children with disabilities. However, only 72% provided wheelchair access and only 68% accepted Medicaid reimbursement. Details of barrier-free design are presented and systems of support for the special needs of disabled patients are described.

Adolescent↗
PubMed1989

Cytochrome P-450-dependent formation of alkylating metabolites of the 2-chloroethylnitrosoureas MeCCNU and CCNU.

Rat liver microsomes catalyzed the biotransformation of the clinically important nitrosourea anticancer agents 1-(2-chloroethyl)-3-(trans-4-methyl-cyclohexyl)-1-nitrosourea (MeCCNU) and 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU) to alkylating metabolites that bound covalently to microsomal protein and to DNA. The enzyme-mediated microsomal alkylation required NADPH and oxygen and was inhibited by carbon monoxide, indicating the participation of a cytochrome P-450-dependent monooxygenase. Additional studies with inhibitors such as piperonyl butoxide and with the inducers 3-methylcholanthrene and phenobarbital were consistent with this view. In contrast to these observations on the formation of alkylating metabolites, carbamylation reactions were not affected significantly by microsomal metabolism. Reduced glutathione, cysteine or N-acetylcysteine decreased the microsomal alkylation by MeCCNU and produced a corresponding increase in the formation of polar metabolites that was resolved by HPLC as three distinct N-acetylcysteine-MeCCNU adducts. The addition of semicarbazide to the reaction decreased microsomal alkylation by 30%, indicating that the formation of the alkylating species may proceed via an aldehyde intermediate. Renal microsomes were not found to catalyze the alkylation reaction. Moreover, MeCCNU inhibited the renal slice accumulation of p-aminohippuric acid only in the presence of liver microsomes and NADPH, suggesting that a liver metabolite may be responsible for the renal toxicity of the parent nitrosourea.

Acetylcysteine↗
PubMed1989

Misplacement of the amino-terminal positive charge in the prepro-alpha-factor signal peptide disrupts membrane translocation in vivo.

We have identified a series of mutations in the signal peptide of yeast prepro-alpha-factor which specifically attenuate translocation across the endoplasmic reticulum membrane in vivo. In prepro-alpha-factor-somatostatin hybrids, transposition of the amino-terminal tripeptide from wild-type NH2-Met-Arg-Phe to NH2-Met-Phe-Lys or NH2-Met-Phe-Arg causes a 45-75% reduction in the efficiency of membrane translocation. This is evidenced by the intracellular accumulation of unglycosylated, signal-containing precursors which are membrane-associated and are exposed to the cytosol. Surprisingly, abolition of the single positive charge by replacing arginine with phenylalanine has little effect on translocation into the endoplasmic reticulum. We conclude that the presence of an amino-terminal positive charge is not necessary for efficient targeting or translocation; however, misplacement by one position markedly disrupts translocation without affecting targeting. These mutations thus define an early stage of membrane interaction that is sensitive to local charge effects. Furthermore, our data suggest that post-translational translocation, signal cleavage, and core glycosylation of these polypeptides may occur to a significant extent in vivo.

Cell Membrane↗