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Biomedical subjects

K Springer

Publications and source records attributed to K Springer.

At least 19 recordsLinked to original sources

Perceptual boundedness and perceptual support in conceptual development.

A theoretical framework for describing the role of perceptual information in early conceptual development is presented. In the main section of the article, a general operationalization of perceptual boundedness is introduced, 3 causes of this limitation are identified, the conditions under which infants and children seem to be perceptually bound are formulated, and the mechanisms by which this limitation declines are described. Traditional claims that young children are perceptually bound, as well as contemporary objections to these claims, are often based on the assumption that perceptual information is generally unveridical or insufficient. Recent doubts about this assumption are evaluated in the final section of the article. It is concluded that although realist arguments are untenable, there are limited forms of perceptual support for conceptual development.

Adult↗

The social geography of AIDS and hepatitis risk: qualitative approaches for assessing local differences in sterile-syringe access among injection drug users.

While significant gains have been achieved in understanding and reducing AIDS and hepatitis risks among injection drug users (IDUs), it is necessary to move beyond individual-level characteristics to gain a fuller understanding of the impact of social context on risk. In this study, 6 qualitative methods were used in combination with more traditional epidemiologic survey approaches and laboratory bioassay procedures to examine neighborhood differences in access to sterile syringes among IDUs in 3 northeastern cities. These methods consisted of (1) neighborhood-based IDU focus groups to construct social maps of local equipment acquisition and drug use sites; (2) ethnographic descriptions of target neighborhoods; (3) IDU diary keeping on drug use and injection equipment acquisition; (4) ethnographic day visits with IDUs in natural settings; (5) interviews with IDUs about syringe acquisition and collection of syringes for laboratory analysis; and (6) focused field observation and processual interviewing during drug injection. Preliminary findings from each of these methods are reported to illustrate the methods' value in elucidating the impact of local and regional social factors on sterile syringe access.

Anthropology, Cultural↗

Structural analysis of the mechanism of adenovirus binding to its human cellular receptor, CAR.

Binding of virus particles to specific host cell surface receptors is known to be an obligatory step in infection even though the molecular basis for these interactions is not well characterized. The crystal structure of the adenovirus fiber knob domain in complex with domain I of its human cellular receptor, coxsackie and adenovirus receptor (CAR), is presented here. Surface-exposed loops on knob contact one face of CAR, forming a high-affinity complex. Topology mismatches between interacting surfaces create interfacial solvent-filled cavities and channels that may be targets for antiviral drug therapy. The structure identifies key determinants of binding specificity, which may suggest ways to modify the tropism of adenovirus-based gene therapy vectors.

Adenoviruses, Human↗

Glutathione S-transferase mu and theta polymorphisms and breast cancer susceptibility.

BACKGROUND: The enzymes encoded by the glutathione S-transferase mu 1 (GSTM1) and theta 1 (GSTT1) genes are involved in the metabolism (mainly inactivation, but activation is possible) of a wide range of carcinogens that are ubiquitous in the environment; the enzyme encoded by the GSTT1 gene may also be active in endogenous mutagenic processes. Homozygous deletions of the GSTM1 and GSTT1 genes are commonly found in the population and result in a lack of enzyme activity. This study was undertaken to evaluate the association between GSTM1 and GSTT1 gene polymorphisms and breast cancer risk. METHODS: Our study included 466 women with incident cases of breast cancer occurring from May 1989 through May 1994 and 466 matched control subjects. These individuals were part of a prospective cohort of U.S. women (i.e., the Nurses' Health Study). Odds ratios (ORs) and 95% confidence intervals (CIs) from conditional logistic regression models were used to estimate the association between genetic polymorphisms and breast cancer risk. RESULTS: The GSTM1 and GSTT1 null genotypes were not associated with an increased risk of breast cancer (OR = 1.05 [95% CI = 0.80-1.37] for GSTM1 null; OR = 0. 86 [95% CI = 0.61-1.21] for GSTT1 null). On the contrary, a suggestion of a decreased risk of breast cancer associated with the GSTT1 null genotype was observed among premenopausal women. When considered together, no combination of the GSTM1 and GSTT1 genotypes was associated with an increased risk of breast cancer. The relationship between GSTM1 and GSTT1 gene deletions and breast cancer risk was not substantially modified by cigarette smoking. CONCLUSIONS: Our data provide evidence against a substantially increased risk of breast cancer associated with GSTM1 and/or GSTT1 homozygous gene deletions.

Breast Neoplasms↗

Coxsackievirus and adenovirus receptor amino-terminal immunoglobulin V-related domain binds adenovirus type 2 and fiber knob from adenovirus type 12.

The extracellular region of the coxsackievirus and adenovirus receptor (CAR) is predicted to consist of two immunoglobulin (Ig)-related structural domains. We expressed the isolated CAR amino-terminal domain (D1) and a CAR fragment containing both extracellular Ig domains (D1/D2) in Escherichia coli. Both D1 and D1/D2 formed complexes in vitro with the recombinant knob domain of adenovirus type 12 (Ad12) fiber, and D1 inhibited adenovirus type 2 (Ad2) infection of HeLa cells. These results indicate that the adenovirus-binding activity of CAR is localized in the amino-terminal IgV-related domain and confirm our earlier observation that Ad2 and Ad12 bind to the same cellular receptor. Preliminary crystallization studies suggest that complexes of Ad12 knob bound to D1 will be suitable for structure determination.

Adenoviruses, Human↗

Pulmonary immunity to Listeria is enhanced by elimination of alveolar macrophages.

To determine how resident alveolar macrophages (AM) regulate the antigen-presenting-cell (APC) activities of pulmonary dendritic cells (DC) in the response to particulate antigen, we pretreated Lewis rats intratracheally with liposomes containing clodronate (LIP-CLOD), which eliminated AM in vivo. Controls received saline encapsulated in liposomes (LIP-SAL) or saline alone intratracheally. At Day 3, rats were injected intratracheally with 1 x 10(7) heat-killed Listeria (HKL) and DC purified from lung were examined for their ability to stimulate HKL-immune T cells without added HKL. Only DC from LIP-CLOD-treated rats displayed enhanced APC activities for HKL. A second intratracheal HKL challenge at Day 14 yielded lymphocytic cuffing of the microvasculature in LIP-CLOD-treated lungs only. Intratracheal adoptive transfer of normal syngeneic AM into LIP-CLOD-treated rats suppressed APC activities of DC in vitro and the lymphocytic response in vivo. Bronchoalveolar macrophages from rats treated with LIP-CLOD and HKL showed decreased production of nitric oxide (NO), a potent suppressor of DC and T-helper 1 lymphocyte activities as compared with those of controls. We conclude that eliminating AM in vivo reduces local production of NO and promotes pulmonary cell-mediated immunity to HKL.

Animals↗

Providing mifepristone-misoprostol medical abortion: the view from the clinic.

In order to gather information about the practical aspects of offering medical abortion, we conducted focus group discussions at each of 17 sites participating in the first large-scale, multi-center trial of mifepristone-misoprostol abortion in the United States. The sites were chosen to represent diverse practice settings (Planned Parenthood affiliates, university research clinics, private practices, and feminist health centers) and geographical regions. Seventy-seven clinic staff members (including counselors, administrators, physicians and other health workers) participated. They discussed the impact of adding a medical method to their clinic structure, their own preferences about offering the method, and their perceptions of women's preferences. Staffing a medical abortion service requires different skills and temperament than those needed for a surgical service. Nearly all participants were eager to begin offering the medical method, and they perceived a strong demand for it on the part of women. They had mixed feelings about the type of provider who should offer the method, but nearly all felt that the regimen could be greatly simplified from the three-visit regimen tested in the trial.

Abortifacient Agents↗

Abortion, revised: participants in the U.S. clinical trials evaluate mifepristone.

This paper centers on the questions: How do non-surgical abortion methods affect private experiences of abortions? How might they influence public conceptions of abortion? Drawing on interviews with clients who participated in the 1994-95 U.S. clinical trials of mifepristone at one trial site (conducted during the trials), and focus group interviews conducted with health care workers at all 17 trial sites (after the trials were completed), we examine participants' evaluations of this method of abortion. Surgical abortion functioned as the reference point by which research participants assessed medical abortion. They discussed mifepristone abortion in terms of nature and invasion, privacy and bodily integrity, denial and agency. Clients frequently portrayed mifepristone abortion as a better moral choice than surgical abortion--in some cases even depicting it as not-really-an-abortion but rather as a miscarriage. Clients felt that mifepristone offered them a greater measure of control over their abortion experiences. Health care providers offered critical analysis of their clients' perceptions, yet affirmed the potential of medical abortion to offer women greater variety and latitude in procreative decision-making, and perhaps even to depoliticize the issue of abortion in the U.S. by thwarting the efforts of anti-abortionists to target providers and aborting women.

Abortifacient Agents, Steroidal↗

Biomechanical evaluation of lateral patellar dislocations.

This investigation was undertaken to identify the structures torn within the medial retinaculum and localize the injury site anatomically following acute lateral dislocation of the patella in a cadaver model. The patellae of 10 fresh-frozen cadavers were translated laterally 135% of the patella width on a universal testing instrument. Magnetic resonance imaging (MRI) was performed on all specimens prior to testing and immediately following testing. Anatomical dissection also was performed on the medial retinaculum following testing. Dissection revealed avulsion fractures from the inferomedial border of the patella in 8 of the 10 knees. The medial patellofemoral ligament was injured in 8 of the 10 knees; the location of the injury varied. Tears of the medial patellofemoral ligament from the femur in 6, a midsubstance tear in 1, and stretch in 1 knee were noted. In a knee with a femoral-sided tear, an avulsion fracture of the medial patellofemoral ligament was identified. None of the cadaver knees demonstrated tears of the lateral retinaculum or medial patellotibial ligaments on dissection. Review of the MRIs revealed a medial retinaculum tear in 6 of the 10 knees. Two tears from the femur, 3 from the patella, and 1 tear from both the patella and femur were noted. An avulsion fracture was noted from the inferomedial patellar border in 3 of the 10 knees. No pathology was noted on 4 of the MRIs. When anatomically correlated, the 3 patellar retinacular tears and 3 avulsion fractures noted on MRI represented a tear of the medial patellomeniscal ligament from the patella. The femoral-sided tear represented a tear of the medial patellofemoral ligament from the femur. An appreciation of the spectrum of injury to the medial retinaculum may aid in the diagnosis of an acute dislocation of the patella and help establish the anatomical structures damaged. The pathology demonstrated in this study may explain the diversity of injury seen clinically. Whereas an avulsion fracture from the patella may represent the medial patellomeniscal ligament, a femoral-sided retinacular tear may represent the medial patellofemoral ligament. This may lead to future refinements of surgical options and anatomic restoration of the damaged structure.

Biomechanical Phenomena↗

Validation of reflectance pulse oximetry: an evaluation of a new sensor in piglets.

OBJECTIVE: A new reflectance pulse oximetry sensor, developed for intrapartum estimation of arterial oxygen saturation (SaO2), was calibrated and evaluated. The sensor contains two light emitting diodes of 735 and 890 nm, and a photodetector at a distance of 14 mm from both light emitting diodes. METHODS: In seven Yorkshire/Hampshire piglets, the reflectance sensor (Nellcor Puritan Bennett Inc.) was calibrated using blood sample SaO2 values. The resulting calibration line was evaluated in four Dutch piglets, by comparing pulse oximetry saturation readings (SpO2) with blood sample and intravascular fiberoptic oximetry SaO2 values. Several reflectance sensors were fixed on each animal. Desaturation levels were obtained by changing the gas mixture of oxygen/ nitrous oxide via a tracheal catheter. RESULTS: In the Yorkshire/ Hampshire piglets, the standard deviation of difference (SpO2-SaO2) was 4.7% (n = 364), over an SaO2 range of 17% to 100%. In the Dutch piglets, the mean difference (SpO2-SaO2) was -1.6% and the standard deviation of difference was 5.4%, over the same SaO2 range (n = 254). Comparisons of continuous recordings of reflectance SpO2 and fiberoptic SaO2 revealed variation in individual regression lines. CONCLUSIONS: This new 735/890 nm reflectance sensor demonstrates acceptable accuracy in piglets. A further evaluation during labor should assess its feasibility for fetal surveillance.

Animals↗

Buffered lidocaine decreases the pain of digital anesthesia in the foot.

The pain associated with injections for inducing digital anesthesia can be decreased by adding sodium bicarbonate to plain lidocaine. A randomized, double-blind study has demonstrated that 24 out of 30 participants indicated on a visual analogue scale that buffered lidocaine is less painful than plain lidocaine. The pain decreased by 50% or more for almost half of the participants. Practitioners can easily buffer lidocaine in the office by adding a small volume of sodium bicarbonate to plain lidocaine.

Adult↗

Glutathione S-transferase class mu deletion polymorphism and breast cancer: results from prevalent versus incident cases.

A common deletion polymorphism in the gene coding for the glutathione S-transferase class mu (the GSTM1 gene) results in a decreased ability to detoxify carcinogenic epoxide intermediates and has been associated with increased breast cancer risk in some small studies. We studied the GSTM1 gene deletion polymorphism (conferring the null genotype) in 243 women who had prevalent breast cancer and 245 women without breast cancer, who were among the 32,826 women in the Nurses' Health Study who gave a blood sample in 1989-1990. In the prevalent case series, the null genotype was slightly more common among cases (58%) than among controls (51%; age-adjusted odds ratio = 1.30; 95% confidence interval, 0.91-1.86). Among cases, the prevalence of the GSTM1 deletion increased with duration of survival [68% for > or = 8 years since diagnosis; 57% for 4-8 years; 51% for < 4 years; P (trend) = 0.04]. In an incident case series of 240 women who were diagnosed with breast cancer following blood collection and prior to June of 1992 and compared with age-matched controls, the GSTM1 deletion was not associated with an elevation in risk (relative risk, 1.08; 95% confidence interval, 0.74-1.57). No significant interaction with cigarette smoking was evident. Thus, there was no significant increase in risk of incident breast cancer associated with the GSTM1 null genotype; however, the gene deletion polymorphism appeared to confer improved survival. These data suggest that odds ratios based upon prevalent cases in molecular epidemiologic studies may be biased due to differential survival. Further studies are required to determine whether this polymorphism is associated with improved breast cancer prognosis.

Adult↗

Associations of delta-aminolevulinic acid dehydratase genotype with plant, exposure duration, and blood lead and zinc protoporphyrin levels in Korean lead workers.

Previous studies have suggested that polymorphisms in delta-aminolevulinic acid dehydratase (ALAD), a heme synthetic enzyme, may be associated with differences in blood lead levels, perhaps due to differential binding of lead in erythrocytes. The authors examined associations of ALAD genotype with blood lead and zinc protoporphyrin (ZPP) levels, exposure duration, sex, and plant in 308 currently exposed lead workers in three lead storage battery manufacturing plants in the Republic of Korea in 1993. The overall prevalence of the variant allele, ALAD2, was 11%, but prevalence varied by plant (p = 0.02: 8.6% in plant A, 20% in plant B, and 22% in plant C). While ALAD2 was not associated with mean blood lead levels, the allele was associated with blood lead levels greater than or equal to 40 micrograms/dl (crude odds ratio (OR) = 2.6, 95% confidence interval (CI) 1.1-6.3; adjusted OR = 2.3, 95% CI 0.8-6.2, with adjustment for sex, plant, and exposure duration) and with exposure durations greater than 6 years (adjusted OR = 2.5, 95% CI 1.2-5.4, with adjustment for blood lead, sex, and plant). Among workers in plant C, the highest exposure plant, ALAD2 was associated with lower ZPP levels when controlling for blood lead levels. These data suggest that lead toxicokinetics may be modified by ALAD genotype and that ALAD2 may be protective for the health effects of lead. ALAD genotype also appears to have been a selection factor for current lead exposure status in the studied workers.

Adult↗

Acquiring a naive theory of kinship through inference.

The present study focused on how children acquire a naive theory of kinship. Young children appear to have theoretical beliefs about the biological meaning of kinship relations. It was argued here that these beliefs reflect inductive inferences from simple facts about prenatal growth (e.g, where babies grow). An informal model of the inferences linking facts to theory was proposed and tested. In Experiment 1, 4-7-year-olds who knew the basic facts of prenatal growth were most likely to also express the naive theory of kinship. Virtually none of the children who expressed the theory were unaware of the basic facts. In Experiment 2, teaching the facts to a sample of preschoolers led to some increase in their acceptance of the kinship theory. Overall, the results implicate a type of theory building that involves inferences from preexisting knowledge rather than structural change, use of analogy, or acquisition of new knowledge.

Child↗

Beliefs about illness causality among preschoolers with cancer: evidence against immanent justice.

Evaluated whether preschoolers with cancer are more or less likely than their healthy counterparts to consider illness a form of punishment for misdeeds (immanent justice). It was found that a sample of preschoolers with cancer (n = 17) rejected immanent justice as a general cause of illness, both in themselves and in others, just as frequently as healthy controls (n = 17). Both groups also rejected immanent justice in cases where misbehavior was prolonged. Children with cancer demonstrated a view of illness causality based on greater differentiation between themselves and other people, in that they were more likely than healthy controls to accept immanent justice as a cause of illness in themselves but not others, and vice versa. Finally, nearly all of the children with cancer who accepted immanent justice as a general cause of illness in themselves also attributed their cancer specifically to immanent justice.

Child, Preschool↗

Thrombin receptor activating peptides: importance of the N-terminal serine and its ionization state as judged by pH dependence, nuclear magnetic resonance spectroscopy, and cleavage by aminopeptidase M.

Peptides derived from the recently identified thrombin receptor were tested for their ability to induce platelet aggregation in platelet-rich plasma. The 14 amino acid peptide identified as the new N-terminus after thrombin cleavage (T-14) and an 11 amino acid peptide (T-11) lacking the 3 C-terminal amino acids of T-14 were studied. Both induced platelet aggregation at micromolar concentrations, with T-11 about twice as potent as T-14. Induction of platelet aggregation by these two peptides showed an unusual pH dependence, being more potent at pH 7.2 than at pH 8.1; thrombin-induced aggregation showed a reverse pH dependence. Proton NMR studies of T-11 demonstrated that the chemical shift of the C-alpha proton of the N-terminal serine had a pH dependence that mirrored the aggregation potency. Acetylating the N-terminus of T-11 resulted in loss of aggregating activity, and this peptide did not show the pH-dependence change in chemical shift. The T-14 and T-11 peptides lost aggregating activity when incubated in plasma due to cleavage of the N-terminal serine by an enzyme identified as aminopeptidase M based on its pattern of inhibition and the ability of purified aminopeptidase M (EC3.4.11.2) to cleave the T-11 peptide. Endothelial cell aminopeptidase M was also able to cleave T-11. Inhibiting aminopeptidase M with amastatin enhanced aggregation induced by T-11 but not thrombin. These studies suggest that ionization of the N-terminus of the T-11 and T-14 peptides may be important in initiating platelet aggregation.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗

Wayfinding on foot from information in retinal, not optical, flow.

People find their way through cluttered environments with ease and without injury. How do they do it? Two approaches to wayfinding are considered: Differential motion parallax (DMP) is a retinal motion invariant of near and far objects moving against fixation; the information in optical flow (IOF) is a radial pattern of vectors, relying on decomposition of retinal flow. Evidence is presented that DMP guides wayfinding during natural gait, accounting for errors as well as correct responses. Evidence against IOF is also presented, and a space-time aliasing artifact that can contaminate IOF displays is explored. Finally, DMP and IOF are separated, showing they can yield different results in different environments. Thus, it is concluded that (a) DMP and IOF are different, (b) DMP and not IOF is used for wayfinding, (c) moving observers do not usually decompose retinal flow, and (d) optical flow may be a mathematical fiction with no psychological reality.

Adult↗