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Biomedical subjects

D Holtzman

Publications and source records attributed to D Holtzman.

At least 19 recordsLinked to original sources
PubMed2001

Altered brain phosphocreatine and ATP regulation when mitochondrial creatine kinase is absent.

In cerebral gray matter, ATP concentration is closely maintained despite rapid, large increases in turnover and low substrate reserves. As seen in vivo by (31)P nuclear magnetic resonance (NMR) spectroscopy, brain ATP is stable early in seizures, a state of high energy demand, and in mild hypoxia, a state of substrate deficiency. Like other tissues with high and variable ATP turnover, cerebral gray matter has high phosphocreatine (PCr) concentration and both cytosolic and mitochondrial creatine kinase (UbMi-CK) isoenzymes. To understand the physiology of brain creatine kinases, we used (31)P NMR to study PCr and ATP regulation during seizures and hypoxia in mice with targeted deletion of the UbMi-CK gene. The baseline CK reaction rate constant (k) was higher in mutants than wild-types. During seizures, PCr and ATP decreased in mutants but not in wild-types. The k-value for the CK catalyzed reaction rate increased in wild-types but not in the mutants. Hypoxic mutants and wild-types showed similar PCr losses and stable ATP. During recovery from hypoxia, brain PCr and ATP concentrations returned to baseline in wild-types but were 20% higher than baseline in the mutants. We propose that UbMi-CK couples ATP turnover to the CK catalyzed reaction rate and regulates ATP concentration when synthesis is increased.

Acid Anhydride Hydrolases↗
PubMed2001

HIV-related behaviors and perceptions among adults in 25 states: 1997 Behavioral Risk Factor Surveillance System.

OBJECTIVES: To assess the level of HIV-related risk behavior among the general US adult population, we analyzed data from the first sexual behavior questions available for states to use with the Behavioral Risk Factor Surveillance System. METHODS: The Behavioral Risk Factor Surveillance System is a state-specific, population-based, random telephone survey. In 1997, 25 states collected sexual behavior data. Annual prevalence estimates for selected behaviors were calculated and examined by sociodemographic characteristics. The correlation between actual and perceived HIV risk also was determined. RESULTS: Most (77.1%) of the respondents reported just 1 sexual partner in the past year; 26.0% reported using a condom at last intercourse. Males, persons who were younger, and Blacks were more likely to report 2 or more partners but also more likely to report using a condom at last intercourse. Only 4.1% of the respondents reported a risk factor for HIV infection; 7.7% reported that they were at medium or high risk for HIV. Actual and perceived HIV risk were positively associated. CONCLUSIONS: Most US adults do not engage in HIV-related risk behavior; those that do are more likely to report protective behavior.

Acquired Immunodeficiency Syndrome↗
PubMed2001

Reliability and validity of measures from the Behavioral Risk Factor Surveillance System (BRFSS).

OBJECTIVES: To assess the reliability and validity of measures on the BRFSS, to assist users in evaluating the quality of BRFSS data, and to identify areas for further research. METHODS: Review and summary of reliability and validity studies of measures on the BRFSS and studies of measures that were the same or similar to those on the BRFSS from other surveys. RESULTS: Measures determined to be of high reliability and high validity were current smoker, blood pressure screening, height, weight, and BMI, and several demographic characteristics. Measures of both moderate reliability and validity included when last mammography was received, clinical breast exam, sedentary lifestyle, intense leisure-time physical activity, and fruit and vegetable consumption. Few measures were of low validity and only one measure was determined to be of low reliability. Several other measures were of high or moderate reliability or validity, but not both. The reliability or validity could not be determined for some measures, primarily due to lack of research. CONCLUSIONS: Most questions on the core BRFSS instrument were at least moderately reliable and valid, and many were highly reliable and valid. Additional research is needed for some measures.

Adult↗
PubMed2000

State- and sex-specific prevalence of selected characteristics--Behavioral Risk Factor Surveillance System, 1996 and 1997.

PROBLEM/CONDITION: High-risk behaviors (e.g., physical inactivity, cigarette smoking, and drinking and driving) and lack of preventive health care (e.g., screening for cancer) are associated with morbidity and mortality from chronic disease and injury. The Behavioral Risk Factor Surveillance System (BRFSS) collects state-specific information to determine the prevalence of such behaviors and preventive practices. By using the BRFSS, states can gain a better understanding of the factors that have a major affect on the health of their adult populations. The BRFSS is also used to monitor progress toward national health objectives. REPORTING PERIOD COVERED: 1996 and 1997. DESCRIPTION OF SYSTEM: The BRFSS is a state-based telephone survey of the civilian, noninstitutionalized, adult (i.e., persons aged 18 years) population. In both 1996 and 1997, 50 states, the District of Columbia, and the Commonwealth of Puerto Rico participated in the BRFSS. RESULTS: As in previous years, state- and sex-specific variations occurred in the prevalence of high-risk behaviors, awareness of certain medical conditions, use of preventive health services, and health-care coverage. For example, in 1997, the percentage of adults who reported being current cigarette smokers ranged from 13.8% to 30.7% among states (median: 23.2%), and the percentage of adults who reported driving after drinking too much alcohol ranged from 0.6% to 5.3% (median: 1.9%). Binge drinking varied substantially not only by state (range: 6.3%-23.3%; median: 14.5%) but also by sex (men: 22.3%; women: 6.7%). Similarly, the prevalence of overweight varied considerably by sex: 62.2% of men and 44.5% of women were overweight in 1997. INTERPRETATION: The 1996 and 1997 BRFSS data demonstrate that U.S. adults engage in behaviors that are detrimental to their health. The data also demonstrate that many adults are making efforts to prevent chronic disease and injury. The prevalence of certain behaviors and health practices differs between states and between men and women. The reasons for these differences by state and sex are subjects for further analysis, but only through continued surveillance can the areas that need further study be identified. PUBLIC HEALTH ACTIONS: Data from the BRFSS are useful in developing and guiding public health programs and policies. For many states, the BRFSS is the only source of state-level data on behaviors and practices related to chronic disease and injury; therefore, BRFSS data are vital for effective decision-making at the local level. States will continue to use these data to help prevent premature morbidity and mortality among their adult population and to assess progress toward national health objectives.

Adult↗
PubMed2000

State-specific prevalence of selected health behaviors, by race and ethnicity--Behavioral Risk Factor Surveillance System, 1997.

PROBLEM/CONDITION: In the United States, disparities in risks for chronic disease (e.g., diabetes, cardiovascular disease, and cancer) and injury exist among racial and ethnic groups. This report summarizes findings from the 1997 Behavioral Risk Factor Surveillance System (BRFSS) of the distribution of access to health care, health-status indicators, health-risk behaviors, and use of clinical preventive services across five racial and ethnic groups (i.e., whites, blacks, Hispanics, American Indians or Alaska Natives, and Asians or Pacific Islanders) and by state. REPORTING PERIOD COVERED: 1997. DESCRIPTION OF SYSTEM: The BRFSS is a state-based telephone survey of the civilian, noninstitutionalized, adult (i.e., persons aged > or = 18 years) population. In 1997, all 50 states, the District of Columbia, and Puerto Rico participated in the BRFSS. RESULTS: Variations in risk for chronic disease and injury among racial and ethnic groups exist both within states and across states. For example, in Arizona, 11.0% of whites, 26.2% of Hispanics, and 50.5% of American Indians or Alaska Natives reported having no health insurance. Across states, the median percentage of adults who reported not having this insurance ranged from 10.8% for whites to 24.5% for American Indians or Alaska Natives. Other findings are as follows. Blacks, Hispanics, American Indians or Alaska Natives, and Asians or Pacific Islanders were more likely than whites to report poor access to health care (i.e., no health-care coverage and cost as a barrier to obtaining health care). Blacks, Hispanics, and American Indians or Alaska Natives were more likely than whites and Asians or Pacific Islanders to report fair or poor health status, obesity, diabetes, and no leisure-time physical activity. Blacks were substantially more likely than other racial or ethnic groups to report high blood pressure. Among all groups, American Indians or Alaska Natives were the most likely to report cigarette smoking. Except for Asians or Pacific Islanders, the median percentage of adults who reported not always wearing a safety belt while driving or riding in a car was > or = 30%. The Papanicolaou test was the most commonly reported screening measure: > or = 81% of white, black, and Hispanic women with an intact uterine cervix reported having had one in the past 3 years. Among white, black, and Hispanic women aged > or = 50 years, > or = 63% reported having had a mammogram in the past 2 years. Approximately two thirds of white, black, and Hispanic women aged > or = 50 years reported having had both a mammogram and a clinical breast examination in the past 2 years; this behavior was least common among Hispanics and most common among blacks. Screening for colorectal cancer was low among whites, blacks, and Hispanics aged > or = 50 years: in each racial or ethnic group, < or = 20% reported having used a home-kit blood stool test in the past year, and < or = 30% reported having had a sigmoidoscopy within the last 5 years. INTERPRETATION: Differences in median percentages between racial and ethnic groups, as well as between states within each racial and ethnic group, are likely mediated by various factors. According to published literature, socioeconomic factors (e.g., age distribution, educational attainment, employment status, and poverty), lifestyle behaviors (e.g., lack of physical activity, alcohol intake, and cigarette smoking), aspects of the social environment (e.g., educational and economic opportunities, neighborhood and work conditions, and state and local laws enacted to discourage high-risk behaviors), and factors affecting the health-care system (e.g., access to health care, and cost and availability of screening for diseases and health-risk factors) may be associated with these differences. ACTION TAKEN: States will continue to use the BRFSS to collect information about health-risk behaviors among various racial and ethnic groups. (ABSTRACT TRUNCATED)

Black or African American↗
PubMed2000

Trends in pregnancy-related smoking rates in the United States, 1987-1996.

CONTEXT: Rates of smoking are increasing among adolescents and young adults, but trends in smoking among pregnant women have not been studied. OBJECTIVE: To assess pregnancy-related variations in smoking behaviors and their determinants among women of childbearing age in the United States. DESIGN: Analysis of data collected between 1987-1996 from the Behavioral Risk Factor Surveillance System survey. SETTING AND SUBJECTS: A total of 187302 (178499 nonpregnant and 8803 pregnant) noninstitutionalized women aged 18 to 44 years from 33 states. MAIN OUTCOME MEASURES: Prevalence rates of smoking initiation and current smoking, median number of cigarettes smoked, and adjusted odds ratios for smoking stratified by pregnancy status; prevalence rate ratio for current smoking comparing pregnant with nonpregnant women. RESULTS: The overall percentage of women who had ever initiated smoking decreased significantly from 44.1% in 1987 to 38.2% in 1996. During that 10-year period, the prevalence of current smoking also decreased significantly among both pregnant women (16.3% to 11.8%) and nonpregnant women (26.7% to 23.6%). Overall, pregnant women were about half (54%) as likely as nonpregnant women to be current smokers during 1987-1996. Over time, the median number of cigarettes smoked per day by pregnant smokers remained at 10, whereas among nonpregnant smokers it decreased from 19 to 15 (P<.05 for trend). In the same period, among young women (aged 18-20 years), prevalence rates of smoking initiation and current smoking increased slightly. Sociodemographic subgroups of women at increased risk for current smoking were the same for pregnant and nonpregnant women (ie, those with a completed high school education or less, whites, and those who were unmarried). CONCLUSIONS: In this analysis, the decline in smoking over time among pregnant women was primarily due to the overall decline in smoking initiation rates among women of childbearing age, not to an increased rate of smoking cessation related to pregnancy. To foster effective perinatal tobacco control, efforts are needed to further reduce the number of young women who begin smoking. Clinicians should query all pregnant women and women of childbearing age about smoking and provide cessation and relapse interventions to each smoker.

Adult↗
PubMed2000

Multi-component apparent diffusion coefficients in human brain: relationship to spin-lattice relaxation.

In vivo measurements of the human brain tissue water signal decay with b-factor over an extended b-factor range up to 6,000 s/mm(2) reveal a nonmonoexponential decay behavior for both gray and white matter. Biexponential parametrization of the decay curves from cortical gray (CG) and white matter voxels from the internal capsule (IC) of healthy adult volunteers describes the decay process and serves to differentiate between these two tissues. Inversion recovery experiments performed in conjunction with the extended b-factor signal decay measurements are used to make separate measurements of the spin-lattice relaxation times of the fast and slow apparent diffusion coefficient (ADC) components. Differences between the spin-lattice relaxation times of the fast and slow ADC components were not statistically significant in either the CG or IC voxels. It is possible that the two ADC components observed from the extended b-factor measurements arise from two distinct water compartments with different intrinsic diffusion coefficients. If so, then the relaxation results are consistent with two possibilities. Either the spin-lattice relaxation times within the compartments are similar or the rate of water exchange between compartments is "fast" enough to ensure volume averaged T(1) relaxation yet "slow" enough to allow for the observation of biexponential ADC decay curves over an extended b-factor range. Magn Reson Med 44:292-300, 2000.

Adult↗
PubMed2000

Lipoproteins in the central nervous system.

Although the synthesis and metabolism of plasma lipoproteins are well characterized, little is known about lipid delivery and clearance within the central nervous system (CNS). Our work has focused on characterizing the lipoprotein particles present in the cerebrospinal fluid (CSF) and the nascent particles secreted by astrocytes. In addition to carrying lipids, we have found that beta-amyloid (A beta) associates with lipoproteins, including the discoidal particles secreted by cultured astrocytes and the spherical lipoproteins found in CSF. We believe that association with lipoproteins provides a means of transport and clearance for A beta. This process may be further influenced by an interaction between A beta and apoprotein E (apoE), the primary protein component of CNS lipoproteins. Specifically, we have investigated the formation and physiologic relevance of a SDS-stable complex between apoE and A beta. In biochemical assays, native apoE2 and E3 (associated with lipid particles) form an SDS-stable complex with A beta that is 20-fold more abundant than the apoE4:A beta complex. In cell culture, native apoE3 but not E4 prevents A beta-induced neurotoxicity by a mechanism dependent on cell surface apoE receptors. In addition, apoE and the inhibition of apoE receptors prevent A beta-induced astrocyte activation. Therefore, we hypothesize that the protection from A beta-induced neurotoxicity afforded by apoE3 may result from clearance of the peptide by SDS-stable apoE3:A beta complex formation and uptake by apoE receptors.

Alzheimer Disease↗
PubMed2000

The feminization of the female oedipal complex, Part I: a reconsideration of the significance of separation issues.

Freud's insights about the oedipus complex have been universalized to include the psychology of the girl. The authors argue that this crucial developmental phase for girls has uniquely feminine characteristics that have not been fully recognized or cohesively incorporated into psychoanalytic theories. This paper addresses these differences, which are based on characteristic patterns of object relationships, typical defenses, and social considerations. The authors argue that "female oedipal" is an oxymoron, and propose that this constellation be named "the Persephone complex" after the Greek myth of Persephone, which seems to capture better the typical situation of the little girl. They focus on the issue of separation and its complicated and necessary role in the triangular situation of females. Using illustrations from clinical material, the authors argue that the frequent appearance of separation material linked to triangular heterosexual competitive fantasies can and should be differentiated from material in which ideas about separation stem from dyadic and earlier issues. Misunderstanding how these separation conflicts tie into triangular "oedipal" relationships can lead to a "preoedipalization" of the dynamics of girls and women.

Adolescent↗
PubMed1999

Multi-component apparent diffusion coefficients in human brain.

The signal decay with increasing b-factor at fixed echo time from brain tissue in vivo has been measured using a line scan Stejskal-Tanner spin echo diffusion approach in eight healthy adult volunteers. The use of a 175 ms echo time and maximum gradient strengths of 10 mT/m allowed 64 b-factors to be sampled, ranging from 5 to 6000 s/ mm2, a maximum some three times larger than that typically used for diffusion imaging. The signal decay with b-factor over this extended range showed a decidedly non-exponential behavior well-suited to biexponential modeling. Statistical analyses of the fitted biexponential parameters from over 125 brain voxels (15 x 15 x 1 mm3 volume) per volunteer yielded a mean volume fraction of 0.74 which decayed with a typical apparent diffusion coefficient around 1.4 microm2/ms. The remaining fraction had an apparent diffusion coefficient of approximately 0.25 microm2/ms. Simple models which might explain the non-exponential behavior, such as intra- and extracellular water compartmentation with slow exchange, appear inadequate for a complete description. For typical diffusion imaging with b-factors below 2000 s/mm2, the standard model of monoexponential signal decay with b-factor, apparent diffusion coefficient values around 0.7 microm2/ms, and a sensitivity to diffusion gradient direction may appear appropriate. Over a more extended but readily accessible b-factor range, however, the complexity of brain signal decay with b-factor increases, offering a greater parametrization of the water diffusion process for tissue characterization.

Adult↗
PubMed1999

In vivo development of brain phosphocreatine in normal and creatine-treated rabbit pups.

To study the effects of creatine (Cr) on brain energy metabolism and on hypoxia-induced seizures, 5- to 30-day-old rabbit pups were given subcutaneous Cr (3 g/kg) for 3 days before exposure to 4% O2 for 8 min. In saline-treated controls, hypoxic seizures were most frequent at 15 days (80% of pups) and 20 days (60%) of age. Seizures were prevented at 15 days and reduced 60% at 20 days in Cr-treated pups. In surface coil-localized brain 31P nuclear magnetic resonance spectra, with signal from both cerebral gray (GM) and white (WM) matter, the phosphocreatine (PCr)/nucleoside triphosphate (NTP) ratio doubled between 5 and 30 days of age in controls. In all Cr-injected pups, brain PCr/NTP increased to values seen in 30-day-old controls. When spectra were acquired in predominantly GM and WM slices in vivo, the PCr/NTP ratio was very low in GM at 5 days but reached adult levels by 15 days in controls. In WM, the ratio increased steadily from 5 to 30 days of age. In Cr-injected pups, PCr/NTP increased to mature levels in WM and in GM at all ages. In conclusion, hypoxic seizures occur midway in the time course of brain PCr/NTP increase in rabbit pups as previously described in rat pups. In both altricial pups, systemic Cr increases brain PCr/NTP ratio and prevents hypoxic seizures. These results suggest that mature levels of PCr and/or Cr in brain limit EEG activation either directly or indirectly by preventing hypoxic metabolic changes.

Adenosine Triphosphate↗
PubMed1998

In vivo phosphocreatine and ATP in piglet cerebral gray and white matter during seizures.

The creatine kinase (CK) reaction is thought to be important in coupling ATP metabolism and regulating ADP concentration in tissues with high and variable ATP turnover, including cerebral gray matter (GM). There is low phosphocreatine (PCr), low CK reaction rates, and high mitochondrial CK (MiCK) isoenzyme activity in GM compared to white matter (WM). To compare the CK reaction in GM and WM when ATP metabolism is high, CK reactants and reaction rates were measured in predominantly GM and WM slices in vivo in 2 and 14-day old piglets during pentylenetetrazole (PTZ) seizures using 31P nuclear magnetic resonance (NMR) 1-dimensional chemical shift imaging (CSI). Arterial pressure, temperature, and blood gasses were stable at both ages. Before seizures, the PCr/nucleoside triphosphate (NTP) ratio was higher in WM than GM at both ages with a developmental increase seen in WM. The CK reaction rate constant increased in both regions between 2 and 14 days. During seizures, PCr/NTP increased in GM at 14 days due to increased PCr while the ratio and PCr decreased in WM. The NTP was more stable in WM and GM at both ages. The CK reaction rate decreased in both regions more at 2 than at 14 days. Thus, brain ATP, deduced from NTP, is stable during seizures in the piglet. In GM stable ATP is associated with a unique increase in PCR concentration.

Adenosine Triphosphate↗
PubMed1998

Brain ATP metabolism in hypoxia resistant mice fed guanidinopropionic acid.

Feeding beta-guanidinopropionic acid (GPA), a competitive inhibitor of creatine transport, decreases mortality and increases brain ATP stability in hypoxic mice. To study brain ATP metabolism in GPA-fed animals, respiratory rates were measured in grey matter and white matter slices as well as cerebral hemisphere mitochondria from GPA-fed mice and rats. Creatine kinase and adenylate kinase activities were measured in rat cerebral grey matter and white matter. Respiratory rates and oxidative phosphorylation were the same in GPA-fed mice and control mice. The adenylate kinase activity increased 50% and creatine kinase showed a small decrease in grey matter. In white matter, creatine kinase increased 50% while adenylate kinase decreased. Thus, GPA produces opposite adaptive changes in adenylate kinase and creatine kinase in grey matter and in white matter. These results suggest that the creatine kinase reaction in grey matter acts to regulate cellular ADP and ATP concentrations.

Adenosine Diphosphate↗
PubMed1998

Creatine increases survival and suppresses seizures in the hypoxic immature rat.

The incidence of clinical seizures is highest in the newborn period. At this developmental stage seizures have many causes, with hypoxia and ischemia thought to be the most common. In rat pups hypoxia produces seizures most frequently at 10-12 d of age. Brain cellular energy metabolism increases between 5 and 25 d of age in the rat, as indicated in vivo by the phosphocreatine (PCr)/nucleoside triphosphate (NTP) ratio measured by 31P nuclear magnetic resonance (NMR) spectroscopy. Brain PCr/NTP ratios are approximately the same in 10-12-d-old rats and human term newborns, the ages of high seizure susceptibility. Thus, low Cr or PCr may be important in susceptibility to hypoxic seizures in the metabolically immature brain. To test this hypothesis, rat pups were injected with Cr for 3 d before exposing them to hypoxia on postnatal d 10 or 20. Before and during hypoxia, the electrocortical activity or 31P nuclear magnetic resonance spectra were measured. At 10 but not 20 d, Cr injections increased brain PCr/NTP ratios, decreased hypoxia-induced seizures and deaths, and enhanced brain PCr and ATP recoveries after hypoxia. Thus, Cr protects the metabolically immature brain from hypoxia-induced seizures and, perhaps, from cellular injury. These results may be directly relevant to the human newborn.

Animals↗
PubMed1998

Persephone, the loss of virginity and the female oedipal complex.

The ancient myth of Persephone and her mother, Demeter, has been characterised as the most important myth about women and the mother-daughter relationship. Previous psychoanalytic interpretations of the myth have neglected its depiction of the girl's defence against a sense of agency over her sexuality. The authors present two examples of the use of this myth by an analytic patient and the writer, Edith Wharton. Both women consciously identified in childhood with the figure of Persephone. Aspects of the myth contributed to a central unconscious fantasy that illuminated their dynamics and sexual conflicts. The authors argue that the Persephone myth is essentially a portrayal of the oedipal dilemma that emphasises a conflict of loyalty towards father and mother, fear of loss of virginity and adult sexuality and a peaceful resolution. The female oedipal conflict is seen as different from that of the male, because the girl competes with the mother on whom she must depend as primary care-giver. Separation issues are encompassed within the female oedipal phase proper. It is proposed that the Persephone complex is better suited to representing women's issues than is the myth of Oedipus.

Adult↗