bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparing attitudes about legal sanctions and teratogenic effects for cocaine, alcohol, tobacco and caffeine: A randomized, independent samples design
Authors: Ginsburg Harvey J , Raffeld Paul , Alanis Kelly L , Boyce Angela S
Published: February 2006

Background

Establishing more sensible measures to treat cocaine-addicted mothers and their children is essential for improving U.S. drug policy. Favorable post-natal environments have moderated potential deleterious prenatal effects. However, since cocaine is an illicit substance having long been demonized, we hypothesized that attitudes toward prenatal cocaine exposure would be more negative than for licit substances, alcohol, nicotine and caffeine. Further, media portrayals about long-term outcomes were hypothesized to influence viewers' attitudes, measured immediately post-viewing. Reducing popular crack baby stigmas could influence future policy decisions by legislators.

In Study 1, 336 participants were randomly assigned to 1 of 4 conditions describing hypothetical legal sanction scenarios for pregnant women using cocaine, alcohol, nicotine or caffeine. Participants rated legal sanctions against pregnant women who used one of these substances and risk potential for developing children.

In Study 2, 139 participants were randomly assigned to positive, neutral and negative media conditions. Immediately post-viewing, participants rated prenatal cocaine-exposed or non-exposed teens for their academic performance and risk for problems at age18.

Results

Participants in Study 1 imposed significantly greater legal sanctions for cocaine, perceiving prenatal cocaine exposure as more harmful than alcohol, nicotine or caffeine. A one-way ANOVA for independent samples showed significant differences, beyond .0001. Post-hoc Sheffe test illustrated that cocaine was rated differently from other substances.

In Study 2, a one-way ANOVA for independent samples was performed on difference scores for the positive, neutral or negative media conditions about prenatal cocaine exposure. Participants in the neutral and negative media conditions estimated significantly lower grade point averages and more problems for the teen with prenatal cocaine exposure than for the non-exposed teen beyond .0001 alpha level. The positive media program closed estimated grade point average differences and risks of later problems to a non-statistically significant margin, p >.05.

Conclusion

Ratings for prenatal cocaine were more negative than comparable ratings for alcohol, nicotine or caffeine exposure. Stereotypes can be reduced, showing viewers that positive postnatal environments ameliorate potential teratogenic effects of cocaine. Reducing negative stereotypes for crack babies may be a requisite for substantive changes in current policy.
Clinical management methods for out-patients with alcohol dependence
Authors: Nalpas Bertrand , Matelak Florence , Martin Sandrine , Boulze Isabelle , Balmes Jean-Louis , Crouzet Corinne
Published: February 2006

Background

In France outpatient centres for the care of alcoholics are healthcare establishments providing medical, psychological and social support. Although they meet the practical needs of these patients, their degree of use in each of these domains and the respective mobilisation of different skills by the care team are not well understood. Our aim was therefore to determine in detail the management involved as a function of the severity of alcohol dependence. For this purpose, all the procedures involved were compiled in a thesaurus describing its type (psychological, medical, social, reception), its scheduled or unscheduled nature, its method (face-to-face, telephone, letter) and its duration. The severity of dependence was evaluated using the Addiction Severity Index (ASI).

Results

45 patients were included and followed-up during 291 ± 114 days. The mean initial ASI scores (± SD) were: medical (M) = 0.39 ± 0.3, working-income (ER) = 0.5 ± 0.3, alcohol (A) = 0.51 ± 0.2, illicit drugs (D) = 0.07 ± 0.08, legal (L) = 0.06 ± 0.13, familial and social environment (FS) = 0.34 ± 0.26, psychological (P) = 0.39 ± 0.22. The total number of procedures was 1341 (29.8 per patient) corresponding to 754.4 hours (16.7 per patient). The intensity of management peaked during the first month of treatment, and then declined rapidly; the maximum incidence of abstinence was observed during the 3rd month of management. Interviews with patients, group therapy and staff meetings represented 68.7%, 9.9% and 13.9% of all procedures, respectively. In patients with severe dependence, as compared to moderate, management was twice as intense in the psychological and social domains, but not in the medical domain.

The ASI questionnaire was completed a second time by 24 patients, after an average of 3.2 months. The improvement was significant in the M, A, D and P domains only.

Conclusion

This study provided an overview of the methods employed in managing a sample of patients consulting an alcoholism centre in line with standards for medical, psychological and social establishments. The predominance of the social and psychological domains over the medical domain was clearly established. Relapses were common after the third month of treatment, but a remobilisation of teams made it possible to contain them. These results provide a framework for discussions on the organisation of healthcare systems and highly suggest that staff need to maintain a constant level of care throughout the treatment process.
Human autoantibodies against the 54 kDa protein of the signal recognition particle block function at multiple stages
Authors: Römisch Karin , Miller Frederick W , Dobberstein Bernhard , High Stephen
Published: February 2006

The 54 kDa subunit of the signal recognition particle (SRP54) binds to the signal sequences of nascent secretory and membrane proteins and it contributes to the targeting of these precursors to the membrane of the endoplasmic reticulum (ER). At the ER membrane, the binding of the signal recognition particle (SRP) to its receptor triggers the release of SRP54 from its bound signal sequence and the nascent polypeptide is transferred to the Sec61 translocon for insertion into, or translocation across, the ER membrane. In the current article, we have characterized the specificity of anti-SRP54 autoantibodies, which are highly characteristic of polymyositis patients, and investigated the effect of these autoantibodies on the SRP function in vitro. We found that the anti-SRP54 autoantibodies had a pronounced and specific inhibitory effect upon the translocation of the secretory protein preprolactin when analysed using a cell-free system. Our mapping studies showed that the anti-SRP54 autoantibodies bind to the amino-terminal SRP54 N-domain and to the central SRP54 G-domain, but do not bind to the carboxy-terminal M-domain that is known to bind ER signal sequences. Nevertheless, anti-SRP54 autoantibodies interfere with signal-sequence binding to SRP54, most probably by steric hindrance. When the effect of anti-SRP autoantibodies on protein targeting the ER membrane was further investigated, we found that the autoantibodies prevent the SRP receptor-mediated release of ER signal sequences from the SRP54 subunit. This observation supports a model where the binding of the homologous GTPase domains of SRP54 and the α-subunit of the SRP receptor to each other regulates the release of ER signal sequences from the SRP54 M-domain.
Serial determination of cyclic citrullinated peptide autoantibodies predicted five-year radiological outcomes in a prospective cohort of patients with early rheumatoid arthritis
Authors: Meyer Olivier , Nicaise-Roland Pascale , Santos Marie dos , Labarre Colette , Dougados Maxime , Goupille Philippe , Cantagrel Alain , Sibilia Jean , Combe Bernard
Published: February 2006

The objective of this study was to evaluate the potential of serially determined anti-cyclic citrullinated peptide (CCP) antibodies for predicting structural joint damage in patients with early rheumatoid arthritis (RA), compared to a single baseline determination. Ninety-nine RA patients with disease durations of less than one year and no history of disease-modifying antirheumatic drug therapy were followed prospectively for at least five years. Anti-CCP2 concentrations were measured using a second-generation ELISA. Sharp scores as modified by van der Heijde were determined on hand and foot radiographs. Anti-CCP2 antibodies were detected in 55.5% of patients at baseline and 63.6% at any time during the first three years. Presence of anti-CCP2 at any time during the first three years was associated with radiographic damage at baseline (odds ratio (OR), 3.66; 95% confidence interval (95% CI) 0.99–13.54) and with five year progression of the total Sharp score (OR, 3.17; 95% CI, 1.3–7.7), erosion score (OR, 5.3; 95% CI, 1.4–19.2) and joint space narrowing score (OR, 2.8; 95% CI, 1.15–6.8). The presence of anti-CCP2 or IgM RF at baseline did not predict these outcomes. Patients with negative anti-CCP2 tests throughout follow-up had less radiographic progression than patients with increasing anti-CCP2 concentrations; they did not differ from patients with decreasing anti-CCP2 antibody levels. HLADRB1* typing showed that progression of the mean modified Sharp score was not correlated with the presence of the shared epitope alleles. In conclusion, serially determined anti-CCP2 antibodies during the first three years of follow-up performs better than baseline determination for predicting radiographic progression in patients with early RA.
Proteoglycan 4 downregulation in a sheep meniscectomy model of early osteoarthritis
Authors: Young Allan A , McLennan Susan , Smith Margaret M , Smith Susan M , Cake Martin A , Read Richard A , Melrose James , Sonnabend David H , Flannery Carl R , Little Christopher B
Published: February 2006

Osteoarthritis is a disease of multifactorial aetiology characterised by progressive breakdown of articular cartilage. In the early stages of the disease, changes become apparent in the superficial zone of articular cartilage, including fibrillation and fissuring. Normally, a monolayer of lubricating molecules is adsorbed on the surface of cartilage and contributes to the minimal friction and wear properties of synovial joints. Proteoglycan 4 is the lubricating glycoprotein believed to be primarily responsible for this boundary lubrication. Here we have used an established ovine meniscectomy model of osteoarthritis, in which typical degenerative changes are observed in the operated knee joints at three months after surgery, to evaluate alterations in proteoglycan 4 expression and localisation in the early phases of the disease. In normal control joints, proteoglycan 4 was immunolocalised in the superficial zone of cartilage, particularly in those regions of the knee joint covered by a meniscus. After the onset of early osteoarthritis, we demonstrated a loss of cellular proteoglycan 4 immunostaining in degenerative articular cartilage, accompanied by a significant (p < 0.01) decrease in corresponding mRNA levels. Early loss of proteoglycan 4 from the cartilage surface in association with a decrease in its expression by superficial-zone chondrocytes might have a role in the pathogenesis of osteoarthritis.
A comparison of transcranial Doppler with near infrared spectroscopy and indocyanine green during hemorrhagic shock: a prospective experimental study
Authors: Bein Berthold , Meybohm Patrick , Cavus Erol , Tonner Peter H , Steinfath Markus , Scholz Jens , Doerges Volker
Published: February 2006

Introduction

The present study was designed to compare cerebral hemodynamics assessed using the blood flow index (BFI) derived from the kinetics of the tracer dye indocyanine green (ICG) with transcranial Doppler ultrasound (TCD) in an established model of hemorrhagic shock.

Methods

After approval from the Animal Investigational Committee, 20 healthy pigs underwent a simulated penetrating liver trauma. Following hemodynamic decompensation, all animals received a hypertonic-isooncotic hydroxyethyl starch solution and either arginine vasopressin or norepinephrine, and bleeding was subsequently controlled. ICG passage through the brain was monitored by near infrared spectroscopy. BFI was calculated by dividing maximal ICG absorption change by rise time. Mean blood flow velocity (FVmean) of the right middle cerebral artery was recorded by TCD. FVmean and BFI were assessed at baseline (BL), at hemodynamic decompensation, and repeatedly after control of bleeding.

Results

At hemodynamic decompensation, cerebral perfusion pressure (CPP), FVmean and BFI dropped compared to BL (mean ± standard deviation; CPP 16 ± 5 mmHg versus 70 ± 16 mmHg; FVmean 4 ± 5 cm·s-1 versus 28 ± 9 cm·s-1; BFI 0.008 ± 0.004 versus 0.02 ± 0.006; p < 0.001). After pharmacological intervention and control of bleeding, FVmean and BFI increased close to baseline values (FVmean 23 ± 9 cm·s-1; BFI 0.02 ± 0.01), respectively. FVmean and BFI were significantly correlated (r = 0.62, p < 0.0001).

Conclusion

FVmean and BFI both reflected the large variations in cerebral perfusion during hemorrhage and after resuscitation and were significantly correlated. BFI is a promising tool to monitor cerebral hemodynamics at the bedside.
Towards a feasible algorithm for tight glycaemic control in critically ill patients: a systematic review of the literature
Authors: Meijering Sofie , Corstjens Anouk M , Tulleken Jaap E , Meertens John HJM , Zijlstra Jan G , Ligtenberg Jack JM
Published: February 2006

Introduction

Tight glycaemic control is an important issue in the management of intensive care unit (ICU) patients. The glycaemic goals described by Van Den Berghe and colleagues in their landmark study of intensive insulin therapy appear difficult to achieve in a real life ICU setting. Most clinicians and nurses are concerned about a potentially increased frequency of severe hypoglycaemic episodes with more stringent glycaemic control. One of the steps we took before we implemented a glucose regulation protocol was to review published trials employing insulin/glucose algorithms in critically ill patients.

Methods

We conducted a search of the PubMed, Embase and Cochrane databases using the following terms: 'glucose', 'insulin', 'protocol', 'algorithm', 'nomogram', 'scheme', 'critically ill' and 'intensive care'. Our search was limited to clinical trials conducted in humans. The aim of the papers selected was required to be glycaemic control in critically ill patients; the blood glucose target was required to be 10 mmol/l or under (or use of a protocol that resulted in a mean blood glucose = 10 mmol/l). The studies were categorized according to patient type, desired range of blood glucose values, method of insulin administration, frequency of blood glucose control, time taken to achieve the desired range for glucose, proportion of patients with glucose in the desired range, mean blood glucose and frequency of hypoglycaemic episodes.

Results

A total of twenty-four reports satisfied our inclusion criteria. Most recent studies (nine) were conducted in an ICU; nine others were conducted in a perioperative setting and six were conducted in patients with acute myocardial infarction or stroke. Studies conducted before 2001 did not include normoglycaemia among their aims, which changed after publication of the study by Van Den Berghe and coworkers in 2001; glycaemic goals became tighter, with a target range between 4 and 8 mmol/l in most studies.

Conclusion

Studies using a dynamic scale protocol combining a tight glucose target and the last two blood glucose values to determine the insulin infusion rate yielded the best results in terms of glycaemic control and reported low frequencies of hypoglycaemic episodes.
Impact of computerized physician order entry on medication prescription errors in the intensive care unit: a controlled cross-sectional trial
Authors: Colpaert Kirsten , Claus Barbara , Somers Annemie , Vandewoude Koenraad , Robays Hugo , Decruyenaere Johan
Published: February 2006

Introduction

Medication errors in the intensive care unit (ICU) are frequent and lead to attributable patient morbidity and mortality, increased length of ICU stay and substantial extra costs. We investigated if the introduction of a computerized ICU system (Centricity Critical Care Clinisoft, GE Healthcare) reduced the incidence and severity of medication prescription errors (MPEs).

Methods

A prospective trial was conducted in a paper-based unit (PB-U) versus a computerized unit (C-U) in a 22-bed ICU of a tertiary university hospital. Every medication order and medication prescription error was validated by a clinical pharmacist. The registration of different classes of MPE was done according to the National Coordinating Council for Medication Error Reporting and Prevention guidelines. An independent panel evaluated the severity of MPEs. We identified three groups: minor MPEs (no potential to cause harm); intercepted MPEs (potential to cause harm but intercepted on time); and serious MPEs (non-intercepted potential adverse drug events (ADE) or ADEs, being MPEs with potential to cause, or actually causing, patient harm).

Results

The C-U and the PB-U each contained 80 patient-days, and a total of 2,510 medication prescriptions were evaluated. The clinical pharmacist identified 375 MPEs. The incidence of MPEs was significantly lower in the C-U compared with the PB-U (44/1286 (3.4%) versus 331/1224 (27.0%); P < 0.001). There were significantly less minor MPEs in the C-U than in the PB-U (9 versus 225; P < 0.001). Intercepted MPEs were also lower in the C-U (12 versus 46; P < 0.001), as well as the non-intercepted potential ADEs (21 versus 48; P < 0.001). There was also a reduction of ADEs (2 in the C-U versus 12 in the PB-U; P < 0.01). No fatal errors occurred. The most frequent drug classes involved were cardiovascular medication and antibiotics in both groups. Patients with renal failure experienced less dosing errors in the C-U versus the PB-U (12 versus 35 serious MPEs; P < 0.001).

Conclusion

The ICU computerization, including the medication order entry, resulted in a significant decrease in the occurrence and severity of medication errors in the ICU.
Rescue treatment with terlipressin in children with refractory septic shock: a clinical study
Authors: Rodríguez-Núñez Antonio , López-Herce Jesús , Gil-Antón Javier , Hernández Arturo , Rey Corsino ,   the RETSPED Working Group of the Spanish Society of Pediatric Intensive Care
Published: February 2006

Introduction

Refractory septic shock has dismal prognosis despite aggressive therapy. The purpose of the present study is to report the effects of terlipressin (TP) as a rescue treatment in children with catecholamine refractory hypotensive septic shock.

Methods

We prospectively registered the children with severe septic shock and hypotension resistant to standard intensive care, including a high dose of catecholamines, who received compassionate therapy with TP in nine pediatric intensive care units in Spain, over a 12-month period. The TP dose was 0.02 mg/kg every four hours.

Results

Sixteen children (age range, 1 month–13 years) were included. The cause of sepsis was meningococcal in eight cases, Staphylococcus aureus in two cases, and unknown in six cases. At inclusion the median (range) Pediatric Logistic Organ Dysfunction score was 23.5 (12–52) and the median (range) Pediatric Risk of Mortality score was 24.5 (16–43). All children had been treated with a combination of at least two catecholamines at high dose rates. TP treatment induced a rapid and sustained improvement in the mean arterial blood pressure that allowed reduction of the catecholamine infusion rate after one hour in 14 out of 16 patients. The mean (range) arterial blood pressure 30 minutes after TP administration increased from 50.5 (37–93) to 77 (42–100) mmHg (P < 0.05). The noradrenaline infusion rate 24 hours after TP treatment decreased from 2 (1–4) to 1 (0–2.5) µg/kg/min (P < 0.05). Seven patients survived to the sepsis episode. The causes of death were refractory shock in three cases, withdrawal of therapy in two cases, refractory arrhythmia in three cases, and multiorgan failure in one case. Four of the survivors had sequelae: major amputations (lower limbs and hands) in one case, minor amputations (finger) in two cases, and minor neurological deficit in one case.

Conclusion

TP is an effective vasopressor agent that could be an alternative or complementary therapy in children with refractory vasodilatory septic shock. The addition of TP to high doses of catecholamines, however, can induce excessive vasoconstriction. Additional studies are needed to define the safety profile and the clinical effectiveness of TP in children with septic shock.
Molecular adsorbent recirculating system and hemostasis in patients at high risk of bleeding: an observational study
Authors: Faybik Peter , Bacher Andreas , Kozek-Langenecker Sibylle A , Steltzer Heinz , Krenn Claus Georg , Unger Sandra , Hetz Hubert
Published: February 2006

Introduction

Liver failure is associated with reduced synthesis of clotting factors, consumptive coagulopathy, and platelet dysfunction. The aim of the study was to evaluate the effects of liver support using a molecular adsorbent recirculating system (MARS) on the coagulation system in patients at high risk of bleeding.

Methods

We studied 61 MARS treatments in 33 patients with acute liver failure (n = 15), acute-on-chronic liver failure (n = 8), sepsis (n = 5), liver graft dysfunction (n = 3), and cholestasis (n = 2). Standard coagulation tests, standard thromboelastography (TEG), and heparinase-modified and abciximab-fab-modified TEG were performed immediately before and 30 minutes after commencement of MARS, and after the end of MARS treatment. Prostaglandin I2 was administered extracorporeally to all patients; 17 patients additionally received unfractioned heparin.

Results

Three moderate bleeding complications in three patients, requiring three to four units of packed red blood cells, were observed. All were sufficiently managed without interrupting MARS treatment. Although there was a significant decrease in platelet counts (median, 9 G/l; range, -40 to 145 G/l) and fibrinogen concentration (median, 15 mg/dl; range, -119 to 185 mg/dl) with a consecutive increase in thrombin time, the platelet function, as assessed by abciximab-fab-modified TEG, remained stable. MARS did not enhance fibrinolysis.

Conclusion

MARS treatment appears to be well tolerated during marked coagulopathy due to liver failure. Although MARS leads to a further decrease in platelet count and fibrinogen concentration, platelet function, measured as the contribution of the platelets to the clot firmness in TEG, remains stable. According to TEG-based results, MARS does not enhance fibrinolysis.
Systematic profiling of cellular phenotypes with spotted cell microarrays reveals mating-pheromone response genes
Authors: Narayanaswamy Rammohan , Niu Wei , Scouras Alexander D , Hart G Traver , Davies Jonathan , Ellington Andrew D , Iyer Vishwanath R , Marcotte Edward M
Published: February 2006

We have developed spotted cell microarrays for measuring cellular phenotypes on a large scale. Collections of cells are printed, stained for subcellular features, then imaged via automated, high-throughput microscopy, allowing systematic phenotypic characterization. We used this technology to identify genes involved in the response of yeast to mating pheromone. Besides morphology assays, cell microarrays should be valuable for high-throughput in situ hybridization and immunoassays, enabling new classes of genetic assays based on cell imaging.
A gold standard set of mechanistically diverse enzyme superfamilies
Authors: Brown Shoshana D , Gerlt John A , Seffernick Jennifer L , Babbitt Patricia C
Published: February 2006

Superfamily and family analyses provide an effective tool for the functional classification of proteins, but must be automated for use on large datasets. We describe a 'gold standard' set of enzyme superfamilies, clustered according to specific sequence, structure, and functional criteria, for use in the validation of family and superfamily clustering methods. The gold standard set represents four fold classes and differing clustering difficulties, and includes five superfamilies, 91 families, 4,887 sequences and 282 structures.
Chemokine- and adhesion-dependent survival of neutrophils after transmigration through cytokine-stimulated endothelium
Authors: McGettrick Helen M , Lord Janet M , Wang Ke-Qing , Rainger G Ed , Buckley Christopher D , Nash Gerard B
Published: February 2006

We examined the fate of neutrophils following transmigration through an endothelial monolayer cultured on “Transwell” membrane filters. Treatment of human umbilical vein endothelial cells (HUVEC) with increasing doses of tumor necrosis factor-α increased the efficiency of transmigration and markedly reduced apoptosis among the transmigrated neutrophils in a dose-dependent manner. Apoptosis was also inhibited after transmigration of neutrophils through HUVEC stimulated with interleukin (IL)-1β but not so effectively after chemotaxis through unstimulated HUVEC driven by IL-8 added below the filter. Inhibition of β2-integrin binding after transmigration or coating the lower chamber with a nonadhesive polymer (polyhydroxyl-ethyl-methacrylate) abrogated neutrophil survival. Although integrin engagement during migration itself was not essential to inhibit apoptosis, activation of neutrophils through CXC chemokine receptors was necessary. Quite brief exposure to the HUVEC (30–120 min) was effective in reducing subsequent apoptosis, although if coincubation with the HUVEC were prolonged, neutrophil apoptosis was reduced further. Neutralization of granulocyte macrophage-colony stimulating factor inhibited this additional effect. Thus, a complex interplay between migration- and activation-dependent signals and adhesive interaction in tissue may combine to effectively prolong the survival of neutrophils recruited during inflammation.
p53 regulates Btk-dependent B cell proliferation but not differentiation
Authors: Schmidt Nathan W , Mayo Lindsey D , Donner David B , Kaplan Mark H
Published: February 2006

Btk is critical for B cell development and proliferation. Mice lacking Btk have a defect in B cell development, resulting in a loss of mature B cells and decreased proliferative responses following B cell receptor cross-linking. In contrast, mice deficient in the tumor suppressor p53 display increases in developing B cell populations in the bone marrow. To investigate the potential role of p53 in Btk-dependent B cell development and function, we generated mice doubly-deficient in p53 and Btk. Btk/p53-deficient mice showed an increase in splenic B220+ cell numbers compared with Btk-deficient mice, although there was no recovery in B cell subset differentiation. In contrast to the lack of recovery of B cell development, there was a recovery in lipopolysaccharide and anti-immunoglobulin M (IgM) plus interleukin-4-induced proliferation of Btk/p53-deficient B cells, although there was no recovery to anti-IgM stimulation alone. Thus, p53 promotes B cell expansion and proliferation, but p53 deficiency cannot compensate for Btk deficiency in the development of B cell subsets.
High-level expression of B7-H1 molecules by dendritic cells suppresses the function of activated T cells and desensitizes allergen-primed animals
Authors: Kim Hee Kyung , Guan Hongbing , Zu Guorui , Li Hui , Wu Lizhi , Feng Xu , Elmets Craig , Fu Yangxin , Xu Hui
Published: February 2006

A body of evidence indicates that expression of the programmed cell death 1 (PD-1) receptor by activated T cells plays an important role in the down-regulation of immune responses; however, the functions of its known ligands, B7-H1 (PD-L1) and B7-dendritic cell (DC; PD-L2), at the effector phase of immune responses are less clear. In the current study, we investigated the roles of B7-H1 in DC-mediated regulation of hapten-activated T cells and the delayed-type contact hypersensitivity response in primed animals. We found that the expression of B7-H1 and B7-DC was induced on activation of DC by hapten stimulation. Blockade of B7-H1, but not B7-DC, enhanced the activity of hapten-specific T cells. Interaction with a DC line that expresses high cell-surface levels of B7-H1 (B7-H1/DC) suppressed the proliferation of, and cytokine production by, activated T cells. In vivo administration of hapten-carrying B7-H1/DC desensitized the response of sensitized animals to hapten challenge, and this desensitization was hapten-specific. These data indicate that B7-H1 expressed by DC mediates inhibitory signals for activated T cells and suppresses the elicitation of immune responses. The ability of B7-H1/DC to inhibit the function of preactivated T cells in vivo suggests novel strategies for the treatment of immune response-mediated disorders.
Impaired dendritic cell function in Crohn’s disease patients with NOD2 3020insC mutation
Authors: Kramer Matthijs , Netea Mihai G , de Jong Dirk J , Kullberg Bart Jan , Adema Gosse J
Published: February 2006

The nucleotide oligomerization domain 2 (NOD2) 3020insC (NOD2fs) mutation increases susceptibility to Crohn’s disease (CD), but the mechanism remains controversial. Loss-of-function and gain-of-function phenotypes have been described as a result of NOD2fs. Here, we show that dendritic cells (DC) derived from CD patients homozygous for this mutation respond normally to purified Toll-like receptor (TLR) ligands but fail to up-regulate the costimulatory molecules CD80 and CD86 in response to the NOD2 ligand muramyl dipeptide (MDP). Moreover, they lack MDP-induced enhancement of TLR-mediated tumor necrosis factor α, interleukin (IL)-12, and IL-10 production, which is observed in control DC with intact NOD2. These data indicate that the NOD2fs mutation results in a loss-of-function phenotype in human myeloid DC and imply decreased immune regulation by IL-10 as a possible mechanism for this mutation in CD.
L-selectin and intercellular adhesion molecule-1 regulate the development of Concanavalin A-induced liver injury
Authors: Kawasuji Ayako , Hasegawa Minoru , Horikawa Mayuka , Fujita Tomoyuki , Matsushita Yukiyo , Matsushita Takashi , Fujimoto Manabu , Steeber Douglas A , Tedder Thomas F , Takehara Kazuhiko , Sato Shinichi
Published: February 2006

Concanavalin A (Con A)-induced hepatitis is a model for human T cell-mediated hepatitis. We evaluated the role of L-selectin and intercellular adhesion molecule-1 (ICAM-1) in this model by injecting Con A intravenously in mice lacking L-selectin (L-selectin−/−), ICAM-1 (ICAM-1−/−), or both (L-selectin/ICAM-1−/−). Blood and liver samples were collected 0, 8, 24, and 48 h after Con A treatment. Increases in plasma transaminase levels, which peaked 8 h after injection, were reduced significantly in L-selectin−/−, ICAM-1−/−, and L-selectin/ICAM-1−/− mice compared with wild-type mice. Liver necrosis was more strongly inhibited in ICAM-1−/− mice than in L-selectin−/− mice but was most prominently reduced in L-selectin/ICAM-1−/− mice, in parallel with decreased plasma transaminase levels. The reduced severity of hepatitis in the mutant mice correlated with decreases in numbers of liver CD4+ T cells but not numbers of CD8+ T cells or neutrophils. Following Con A treatment, L-selectin deficiency reduced liver mRNA expression of tumor necrosis factor-α, and ICAM-1 deficiency reduced expression of interleukin-4. By contrast, reductions in liver macrophage inhibitor protein-1α mRNA occurred in all mutant mice. These results indicate that L-selectin and ICAM-1 contribute cooperatively to the development of Con A-induced hepatitis by regulating leukocyte infiltration and subsequent cytokine production.
Sex-specific phenotypical and functional differences in peripheral human Vγ9/Vδ2 T cells
Authors: Caccamo Nadia , Dieli Francesco , Wesch Daniela , Jomaa Hassan , Eberl Matthias
Published: February 2006

Vγ9/Vδ2 T cells constitute a minor proportion of human peripheral blood T cells that can expand rapidly upon infection with microbial pathogens. Vγ9/Vδ2 T cell numbers change characteristically with age, rising from birth to puberty and gradually decreasing again beyond 30 years of age. In adults, female blood donors have significantly higher levels than males, implying that circulating Vγ9/Vδ2 T cells in women remain elevated for a longer period in life and drop less strikingly than in men. This loss in men is accompanied by a substantial depletion of CD27−CD45RA− and CD27−CD45RA+ effector T cells and a parallel increase in CD27+CD45RA− central memory T cells while in women, the distribution of Vγ9/Vδ2 T cell subsets remains virtually unchanged. The phenotypical conversion in men older than 30 years is mirrored by an increased proliferative response of Vγ9/Vδ2 T cells and a reduced interferon-γ secretion upon stimulation with isopentenyl pyrophosphate in vitro.
Psychiatric genetic research at the National Institute of Mental Health
Authors: Berg Kate , Mullican Charlotte , Maestri Nancy , Shore David
Published: February 2006

For some time it has been known through the results of family, twin, and adoption studies that heredity appears to play a significant causal role in many mental disorders, including schizophrenia, bipolar disorder, and other mood disorders, Alzheimer's Disease, panic disorder, obsessive compulsive disorder, autism, dyslexia, and Tourette's Syndrome. The precise patterns of inheritance of these complex disorders have not been determined, nor have the relevant genes been localized or cloned. Because the genetics are complex and because there is also clearly an environmental contribution to behavior, we expect the analysis of the genetics of mental illness to be arduous, and not quickly resolved. There are several compelling reasons to continue to focus our attention on uncovering the genetic factors for severe mental illness. Prominent among these are the implications for better treatment of mental disorders. The National Institute of Mental Health supports a wide range of studies on psychiatric genetic research. © 1994 Wiley‐Liss, Inc.
Report from the Maryland epidemiology schizophrenia linkage study: No evidence for linkage between schizophrenia and a number of candidate and other genomic regions using a complex dominant model
Authors: Karayiorgou Maria , Kasch Laura , Lasseter Virginia K. , Hwang Jennifer , Elango Ramu , Bernardini D. Jonathan , Kimberland Michelle , Babb Robert , Francomano Clair A. , Wolyniec Paula S. , Lamacz Malgorzata , Nestadt Gerald , Meyers Deborah , Ott Jurg , Childs Barton , Antonarakis Stylianos , Kazazian Haig H. , Housman David E. , Pulver Ann E.
Published: February 2006

Our collaborative group has undertaken a linkage study of schizophrenia, using a systematic sample of patients admitted to Maryland hospitals. An initial sample of 39 families, each having two or more affecteds, was available for genotyping candidate genes, candidate regions, and highly polymorphic markers randomly distributed throughout the genome. We used a single complex dominant model (with a disease gene frequency of 0.005 and age‐dependent penetrance for affected phenotype: for under 35, penetrance = .45; for 35 and older, penetrance = .85). We report here 130 markers, which met the exclusion criteria of LOD score <−2.00 at theta >0.01 in at least 10 informative families, and no evidence for heterogeneity. We also report here markers that were tested as candidates for linkage to the schizophrenic phenotype. They were selected based on the following criteria: (a) proximity to reported chromosomal rearrangements (both 5q and 11q), (b) suggestions of linkage from other families (5q), or (c) presence of a candidate gene (5q, 11q, 3q: Dopamine receptors 1, 2, and 3, respectively). We also tested for mutations of codon 717 in exon 17 of the amyloid precursor protein (APP) gene and were unable to detect the C to T substitution in our schizophrenic group. © 1994 Wiley‐Liss, Inc.
No allelic association between Parkinson's disease and dopamine D2, D3, and D4 receptor gene polymorphisms
Authors: Nanko Shinichiro , Ueki Akira , Hattori Mineko , Dai Xiao Y. , Sasaki Tsukasa , Fukuda Rimmei , Ikeda Kazuhiko , Kazamatsuri Hajime
Published: February 2006

Parkinson's disease is thought to be caused by a combination of unknown environmental, genetic, and degenerative factors. Evidence from necropsy brain samples and pharmacokinetics suggests involvement of dopamine receptors in the pathogenesis or pathophysiology of Parkinson's disease. Genetic association studies between Parkinson's disease and dopamine D2, D3 and D4 receptor gene polymorphisms were conducted. The polymorphism was examined in 71 patients with Parkinson's disease and 90 controls. There were no significant differences between two groups in allele frequencies at the D2, D3, and D4 dopamine receptor loci. Our findings do not support the hypothesis that susceptibility to Parkinson's disease is associated with the dopamine receptor polymorphisms examined. © 1994 Wiley‐Liss, Inc.
Phenotypic definitions of psychotic illness for molecular genetic research
Authors: Farmer Anne E. , Williams Julie , Jones Irene
Published: February 2006

New approaches to establish the molecular genetic bases of psychotic illness have recently been suggested which make different demands on diagnosticians attempting to provide reliable and valid phenotypic definitions. The diagnostic problems that have arisen to date and some solutions to these are considered. In addition, future diagnostic requirements for linkage and association studies are discussed. © 1994 Wiley‐Liss, Inc.
Dopamine D4 receptor variant, D4GLYCINE194, in Africans, but not in Caucasians: No association with Schizophrenia
Authors: Seeman Philip , Ulpian Carla , Chouinard Guy , Van Tol Hubert H. M. , Dwosh Hy , Lieberman Jeffrey A. , Siminovitch Katherine , Liu Ivy S. C. , Waye John , Voruganti P. , Hudson Craig , Serjeant Graham R. , Masibay Arni S. , Seeman Mary V.
Published: February 2006

Because antipsychotic drugs selectively block dopamine receptors and since dopamine D4 receptors are elevated sixfold in postmortem schizophrenia brain, we searched for possible abnormalities in the coding region of the genomic DNA sequence for the dopamine D4 receptor in control and schizophrenia tissues. The DNA sequence for the first 250 bases of exon 3 of this receptor was examined in the genomic DNA from 296 control individuals and 58 schizophrenics. Twenty‐three out of 183 control blacks (12.6%) and 3 out of 24 (12.5%) schizophrenic blacks revealed a replacement of T by G, predicting a substitution of valine by glycine at amino acid position 194. The identical prevalence of 12.5% indicates that the variant is not associated with schizophrenia. The amino acid replacement occurs one amino acid away from a serine amino acid which is critical for the attachment of dopamine. None of the 147 Caucasians (113 controls; 34 schizophrenics) revealed this variant, termed D4GLYCINE194. © 1994 Wiley‐Liss, Inc.
Blood groups of apes and monkeys. VII. The human‐type A‐B‐H factors in gelada monkeys (Theropithecus gelada)
Authors: Wiener A. S. , Moor‐Jankowski J. , Gordon Eve B.
Published: February 2006

A series of 21 gelada monkeys (Theropithecus gelada) all showed strong reactivity of their saliva for H substance, but no reactivity for either A or B. Tests on their sera in no case showed the simultaneous presence of both the agglutinins anti‐A and anti‐B; instead some animals had only anti‐A, others had only anti‐B, while the remainder had neither anti‐A nor anti‐B. These findings distinguish gelada monkeys from all other species of Old World monkeys tested to date. They also provide further evidence supporting the genetic independence of the H substance and the A‐B‐O blood groups.
Blood groups of Cakchiquel Indians from Sumpango, Guatemala
Authors: Walker Mary , Allen Fred H. , Newman Marshall T.
Published: February 2006

ABO, MN, Rh, P, Lutheran, Kell, Duffy and Kidd blood group systems were studied in a sample of 135 Cakchiquel‐speaking Indians from Sumpango, Dpto. Sacatepequez, Guatemala. Sumpango represents an almost exclusively endogamous isolate in the western highlands some 42 km outside of Guatemala City. The bloods were collected by families, and tests on them are much more revealing than on unrelated individuals because the genotypes are so often evident, and genes that could not have been otherwise detected are revealed. What is lost in numbers of unrelated people is probably more than compensated for by the precision of gene identification.

Some evidence of foreign genes in this Indian sample is afforded by gene B in a mother and three of her children, in a small frequency (0.01) of R−2,−3 (cde or cDe), and perhaps in gene MU or Mu in a mother and son. Gene frequencies for the Sumpango sample are very similar to those of Matson and Swanson's ('63) Cakchiquel from nearby Chimaltenango and Patzicia. The Sumpango sample shows lower P and Jka and higher R2,−3 (CDe), and of these the low P and high R2,−3 stand outside of the known Maya range.
Cranial capacity and neuron number: A critique and proposal
Authors: Holloway Ralph L.
Published: February 2006

Some recent studies correlating cranial capacity with behavioral development and more molecular parameters such as neuron number are critically examined. These studies are found lacking in terms of basic assumptions and empirical support from other studies. In general, it is shown that these studies have overlooked an important aspect of brain evolution in the Primate Order, i.e., reorganization, or the shifting quantitative relationships of subsystems and components of the nervous system. A distinction is made between two approaches to the problem of the evolution of brain and behavior: (1) the “quantitative‐specific” and (2) the “quantitative‐general.” Attempts to derive specificity in terms of estimates of the number of cortical neurons in different pongid and hominid brains are premature unless basic data regarding organizational shifts are known. A supporting argument for the priority of the “quantitative‐general” approach for all levels of the primate nervous system is made. Such a descriptive level is more amenable to synthesis with current neurophysiological knowledge and primate field and laboratory studies than the “quantitative‐specific” approach.
Monkey locomotion on inclined surfaces
Authors: Prost J. H. , Sussman R. W.
Published: February 2006

Motion pictures were taken of a subadult, female squirrel monkey moving on level and inclined surfaces. The gaits for the various degrees of incline were compared. The noncontact periods were not affected by changes in inclination. The contact periods, which were inversely related to speed, were affected, by changes in slope and intersect constants. When the incline was steep the animal was forced to jump and zig‐zag to retain its progression. The affect of inclination was advantageous at 16° and disadvantageous at higher and lower inclines. At the 16° inclination the animal's short fore legs and long hind legs held the body horizontal, cancelling the effect of the incline. It is reasoned that limb proportions may be adaptive for progression on inclined surfaces and that the locomotor niches for the various arboreal primates may be usefully categorized in terms of the inclinations of their substrates.
Fingerprints of Whites and Negroes from Southern Brazil
Authors: de sá E Benevides Fº F. R. , Salzano F. M.
Published: February 2006

Studies on 1,115 individuals (451 Whites, 240 Light Mulattoes, 236 Dark Mulattoes and 188 Negroes) from Pôrto Alegre, Brazil are reported. The differences among those subgroups are not large and there is not a clear gradient when we consider samples with increasing Negro ancestry. The most marked difference between Whites and the total Negroid group occurred in the prevalence of radial loops. Comparison with Portuguese and African series indicates that no single factor can fully explain the observed distributions. But the values of Dankmeijer's index are exactly those expected on the assumption of 50% White admixture in the Pôrto Alegre Negro, in agreement with previous investigations.
Anthropometric changes associated with high altitude acclimatization in females
Authors: Hannon John P. , Shields J. L. , Harris Charles W.
Published: February 2006

The anthropometric effects of prolonged high altitude exposure were studied in eight college women who lived on the summit of Pikes Peak (14,100 ft.) for 2.5 months. Acclimatization to altitude was associated with a decrease of skin‐fold thickness and a reduction in limb circumference, but little change in body weight. It was concluded that these changes reflected a loss of subcutaneous fat during the period of altitude exposure. Altitude exposure did not produce any alterations in trunk circumference at the umbilicus or buttocks, but it did cause an increase in the inspiratory chest circumference at the axillary level and a reduction in expiratory chest circumference at the subscapular level.
Bilateral symmetry in finer lines of increased density
Authors: Garn Stanley M. , Baby Raymond S.
Published: February 2006

Radiogrammetric comparisons of the left and right femora of adult archaic Indian Knoll specimens from Kentucky show bilateral correspondence in more than 50% of “key” lines of increased radiographic density, indicating the symmetrical nature of the original developmental events.
The skin of primates. XLIII. Further observations on the Philippine tarsier (Tarsius syrichta)
Authors: Arao T. , Perkins E.
Published: February 2006

Underneath the volar friction surfaces is a highly developed, anastomosing system of alkaline phosphatase‐reactive capillaries; numerous cholinesterase‐positive hederiform nerve end‐organs are present in the scalp, forehead, lower abdomen, back, and perianal region; sinus hair follicles occur on the flexor surface of the antebrachium; and a dense field of gigantic sebaceous and admixed apocrine glands constitutes the epigastric gland.
The basal area of posterior tooth crown components: The assessment of within tooth variations of premolars and molars
Authors: Biggerstaff Robert H.
Published: February 2006

This paper presents the basic hypotheses and methods for describing the basal area, the projected relative plane surface areas of molar and premolar crown components. Basically these methods utilize definable anatomical landmarks which are projected from the occlusal surface of the posterior teeth to the occlusal plane. The relative plane surface area, a projection of the basal surface area, can be described by a series of vectors which outline each crown component as a polygon. The description of the dentition in this way is essential to a variety of experimental designs, i.e., the analysis of the range of variation of occulsion, the measuring and expression of shape and the description of the “within tooth” variations in size and position of each crown component.
ABO hemolytic disease of the newborn as a selection mechanism at the ABO locus
Authors: Sever Lowell E.
Published: February 2006

Data from the period 1951 to 1967 were collected from the records at the Milwaukee Blood Center on 380 cases of ABO hemolytic disease to determine if ABO incompatibility may be regarded as a selection mechanism at the ABO locus. In comparison with infants of ABO compatible parents the affected infants had significantly lower hemoglobin and hematocrit values and higher bilirubin concentrations. Forty‐eight percent of the affected showed a positive direct antiglobulin test, 81% showed increased numbers of reticulocytes and 92% had spherocytosis. Since affected infants are considered to be in grave danger when high concentrations of bilirubin are present it is significant that 169 individuals (44%) required exchange transfusions. Compared with the number of live births in Milwaukee for the same period this represents a frequency of one in every 1,654 live births so that ABO incompatibility may be regarded as an important mechanism of natural selection. Since it was found that 98.7% of the mothers of the affected infants are of blood group O, the affected infants are therefore heterozygous (AO or BO) and selection due to ABO incompatibility would have its greatest effect upon the lowest allele frequencies in a population.