bluuebunny/crossref_metadata_2025 huggingface dataset:
Aortic arginine transport is attenuated, through post-translational modulation of CAT-1 by PKCα, in old male rats
Authors: Schwartz Idit F , Chernichovski Tamara , Schwartz Doron
Published: October 2009

Experimental models using rats suggest that decreased endothelial nitric oxide synthase (eNOS) activity in old males promotes renal atherosclerosis, whereas females are protected. We aimed to explore whether aging alters aortic arginine uptake by CAT-1, the selective arginine supplier to eNOS in rats. Arginine uptake by freshly harvested aortic rings from young males (9 weeks) was significantly higher than in young females. Old males (18 months) exhibited a significant decrease in arginine transport compared to young males, whereas no differences were observed between old and young females. Cationic amino acid transporter-1 (CAT-1) abundance remained unchanged in all experimental groups. The abundance of protein kinase C α (PKCα), a CAT-1 inhibitor, was significantly augmented in old versus young males while no differences were detected between old and young females. Phosphorylated PKCα was significantly increased in old rats of both sexes. αTocopherol, a PKC inhibitor, produced a significant increase in arginine transport in old males only. In conclusion, aortic arginine transport by CAT-1 is attenuated in old male rats through upregulation of PKCα. In old females, aortic arginine transport is protected from the effects of PKCα by an unknown mechanism.
Robustness for general design mixed models using the t-distribution
Authors: Staudenmayer J , Lake E E , Wand M P
Published: October 2009

The t-distribution allows the incorporation of outlier robustness into statistical models while retaining the elegance of likelihood-based inference. In this paper, we develop and implement a linear mixed model for the general design of the linear mixed model using the univariate t-distribution. This general design allows a considerably richer class of models to be fit than is possible with existing methods. Included in this class are semi-parametric regression and smoothing and spatial models.
Review: Androgens, erectile dysfunction and cardiovascular risk in type 2 diabetes
Authors: Hackett Geoffrey I
Published: October 2009

Men with type 2 diabetes now require annual assessment for erectile dysfunction, and this should include assessment for testosterone deficiency. Up to 40% of patients might be candidates for testosterone replacement for the treatment of bothersome symptoms including erectile dysfunction, lethargy, fatigue, loss of libido and depressed mood. There is emerging evidence that there may also be benefits in the primary care quality parameters for type 2 diabetes.
Promoting Policy and Environmental Change Using Photovoice in the Kaiser Permanente Community Health Initiative
Authors: Kramer Leila , Schwartz Pamela , Cheadle Allen , Borton J. Elaine , Wright Merrick , Chase Charlie , Lindley Corina
Published: October 2009

Creative ways must be found to engage both community residents and political leaders around policy and environmental solutions to public health issues. Photovoice is a community-based, participatory approach to documentary photography that provides people with training on photography, ethics, critical discussion, and policy advocacy. Photovoice projects have been implemented across the nation as part of Kaiser Permanente’s Community Health Initiative—a community-based obesity prevention effort. This article focuses on the first Photovoice project implemented in three communities in Colorado. Photovoice themes related to healthy eating and active living include a lack of access to healthy food choices in stores and schools, unsafe street crossings and sidewalks, and the need to redevelop certain areas to encourage safe recreation. The involvement of policy leaders in the project combined with several dissemination activities has contributed to healthier food offerings in schools and neighborhoods and city planning efforts that emphasize walkability and access to healthy food, and park revitalization.
Structural characteristics of the subscapularis muscle in children with medial rotation contracture of the shoulder after obstetric brachial plexus injury
Authors: Hultgren T. , Einarsson F. , Runesson E. , Hemlin C. , Fridén J. , Ljung B.-O.
Published: October 2009

The aim of this study was to obtain a better understanding of the cause of the medial rotation contracture of the shoulder after obstetric brachial plexus lesions by studying the morphology of the shortened subscapularis muscle. Muscle biopsy specimens were harvested from 13 children with obstetric brachial plexus palsy who underwent corrective surgery for the rotation contracture. The majority of the subscapularis muscle biopsy samples had an essentially normal morphology and showed a predominance of type I myosin heavy chain isoform, while one biopsy showed signs of marked fibrosis and a predominance of type II myosin heavy chain isoform. The findings support the assumption that shortening of the subscapularis is caused primarily by the nerve injury, which weakens the antagonistic lateral rotators, but that direct injury to the muscle might be a contributory factor.
Themo-elasto-viscoplastic modelling of friction stir welding
Authors: Qin X. , Michaleris P.
Published: October 2009

A coupled two-dimensional Eulerian thermo-elasto-viscoplastic model has been developed for modelling the friction stir welding process. First, a coupled thermo-viscoplastic analysis is performed to determine the temperature distribution in the full domain and the incompressible material flow around the spinning tool. Next, an elasto-viscoplastic analysis is performed outside the viscoplastic region to compute the residual stress. Both frictional heat and plastic deformation heat generation are considered in the model. Furthermore, this is the only known model computing residual stress accounting for plasticity caused by both thermal expansion and mechanical deformation due to material spinning. The computed residual stress is verified by comparing to experimentally measured data.
Stationary GMAW-P weld metal deposit spreading
Authors: Lim Y. C. , Farson D. F. , Cho M. H. , Cho J. H.
Published: October 2009

Non-isothermal spreading of non-travelling pulsed gas metal arc weld (GMAW-P) deposits was studied by experiments and numerical simulation. After an initial transient period, metal from the melting welding wire was deposited as a regular stream of droplets into a molten weld pool whose spreading was enhanced by direct arc heating of the solid substrate and weld pool convection. Accurate predictions of the final weld cross-section and time histories of base metal temperature and weld pool radius were produced by this simulation, which included mass, energy and momentum of transferring filler metal droplets. Dimensional analysis showed that speed of weld pool spreading was initially dominated by the momentum of liquid droplets while thermal convection by surface tension-driven flow became important at intermediate times. Eventually, the rate of spreading was matched to the thermal diffusion rate in the liquid. Capillary forces were never important in weld pool spreading. The weld metal deposit shape was well-approximated as a spherical cap with increasing volume and constant contact angle.
Differential requirement for Gata1 DNA binding and transactivation between primitive and definitive stages of hematopoiesis in zebrafish
Authors: Belele Christiane L. , English Milton A. , Chahal Jagman , Burnetti Anthony , Finckbeiner Steven M. , Gibney Gretchen , Kirby Martha , Sood Raman , Liu P. Paul
Published: October 2009

The transcription factor Gata1 is required for the development of erythrocytes and megakaryocytes. Previous studies with a complementation rescue approach showed that the zinc finger domains are required for both primitive and definitive hematopoiesis. Here we report a novel zebrafish gata1 mutant with an N-ethyl-N-nitrosourea–induced point mutation in the C-finger (gata1T301K). The Gata1 protein with this mutation bound to its DNA target sequence with reduced affinity and transactivated inefficiently in a reporter assay. gata1T301K/T301K fish had a decreased number of erythrocytes during primitive hematopoiesis but normal adult hematopoiesis. We crossed the gata1T301K/T301K fish with those carrying the R339X mutation, also known as vlad tepes (vlt), which abolishes DNA binding and transactivation activities. As we reported previously, gata1vlt/vlt embryos were “bloodless” and died approximately 11 to 15 days after fertilization. Interestingly, the gata1T301K/vlt fish had nearly a complete block of primitive hematopoiesis, but they resumed hematopoiesis between 7 and 14 days after fertilization and grew to phenotypically normal fish with normal adult hematopoiesis. Our findings suggest that the impact of Gata1 on hematopoiesis correlates with its DNA-binding ability and that primitive hematopoiesis is more sensitive to reduction in Gata1 function than definitive hematopoiesis.
How I treat hairy cell leukemia
Authors: Grever Michael R.
Published: October 2009

The description of hairy cell leukemia as a specific clinical entity was published 50 years ago. The clinical outcome for patients was hampered by ineffective chemotherapy, and splenectomy was the major therapeutic approach to improve peripheral blood counts. The median survival after diagnosis was 4 years. With the introduction of α-interferon in 1984, marked improvements in patient responses were observed. Shortly thereafter, the introduction of the purine nucleoside analogs transformed this disease into a highly treatable form of leukemia, and patients with the classic form of this rare leukemia now have a near-normal life expectancy. However, other clinical entities mimicking this disease do not respond; thus, accurate diagnosis is important. Immunophenotypic features in classic hairy cell leukemia show that the leukemic cells express CD11c, CD25, CD103, and CD123 and display bright CD20. Despite the high percentage of durable complete remissions with modern therapy, the long-term disease-free survival curves have not reached a plateau. Many patients who achieve a complete remission by morphologic criteria have minimal residual disease demonstrable by either flow cytometry or immunohistochemical staining, and this population may be at higher risk for earlier relapse. Continued clinical research is essential to optimize therapy for this disease.
Brief Communication: Economic Comparison of Opportunistic Infection Management With Antiretroviral Treatment in People Living With HIV/AIDS Presenting at an NGO Clinic in Bangalore, India
Authors: John KR , Rajagopalan Nirmala , Madhuri Nirmala
Published: October 2009

Context

Highly active antiretroviral treatment (HAART) usage in India is escalating. With the government of India launching the free HAART rollout as part of the “3 by 5” initiative, many people living with HIV/AIDS (PLHA) have been able to gain access to HAART medications. Currently, the national HAART centers are located in a few district hospitals (in the high‐ and medium‐prevalence states) and have very stringent criteria for enrolling PLHA. Patients who do not fit these criteria or patients who are too ill to undergo the prolonged wait at the government hospitals avail themselves of nongovernment organization (NGO) services in order to take HAART medications. In addition, the government program has not yet started providing second‐line HAART (protease inhibitors). Hence, even with the free HAART rollout, NGOs with the expertise to provide HAART continue to look for funding opportunities and other innovative ways of making HAART available to PLHA. Currently, no study from Indian NGOs has compared the direct and indirect costs of solely managing opportunistic infections (OIs) vs HAART.

Objective

Compare direct medical costs (DMC) and nonmedical costs (NMC) with 2005 values accrued by the NGO and PLHA, respectively, for either HAART or exclusive OI management.

Study design

Retrospective case study comparison.

Setting

Low‐cost community care and support center ‐ Freedom Foundation (NGO, Bangalore, south India).

Patients

Retrospective analysis data on PLHA accessing treatment at Freedom Foundation between January 1, 2003 and January 1, 2005. The HAART arm included case records of PLHA who initiated HAART at the center, had frequent follow‐up, and were between 18 and 55 years of age. The OI arm included records of PLHA who were also frequently followed up, who were in the same age range, who had CD4+ cell counts < 200/microliter (mcL) or an AIDS‐defining illness, and who were not on HAART (solely for socioeconomic reasons). A total of 50 records were analyzed. Expenditures on medication, hospitalization, diagnostics, and NMC (such as food and travel for a caregiver) were calculated for each group.

Results

At 2005 costs, the median DMC plus NMC in the OI group was 21,335 Indian rupees (Rs) (mean Rs 24,277/‐) per patient per year (pppy) (US $474). In the HAART group, the median DMC plus NMC was Rs 18,976/‐ (mean Rs 21,416/‐) pppy (US $421). Median DMC plus NMC pppy in the OI arm was Rs 13623.7/‐ paid by NGO and Rs 1155/‐ paid by PLHA. Median DMC and NMC pppy in the HAART arm were Rs 1425/‐ paid by NGO and Rs 17,606/‐ paid by PLHA.

Conclusion

Good health at no increased expenditure justifies providing PLHA with HAART even in NGO settings.
Increased cardiac index due to terbutaline treatment aggravates capillary-alveolar macromolecular leakage in oleic acid lung injury in dogs
Authors: Briot Raphael , Bayat Sam , Anglade Daniel , Martiel Jean-Louis , Grimbert Francis
Published: October 2009

Introduction

We assessed the in vivo effects of terbutaline, a beta2-agonist assumed to reduce microvascular permeability in acute lung injury.

Methods

We used a recently developed broncho-alveolar lavage (BAL) technique to repeatedly measure (every 15 min. for 4 hours) the time-course of capillary-alveolar leakage of a macromolecule (fluorescein-labeled dextran) in 19 oleic acid (OA) lung injured dogs. BAL was performed in a closed lung sampling site, using a bronchoscope fitted with an inflatable cuff. Fluorescein-labeled Dextran (FITC-D70) was continuously infused and its concentration measured in plasma and BAL fluid. A two-compartment model (blood and alveoli) was used to calculate KAB, the transport rate coefficient of FITC-D70 from blood to alveoli. KAB was estimated every 15 minutes over 4 hours. Terbutaline intra-venous perfusion was started 90 min. after the onset of the injury and then continuously infused until the end of the experiment.

Results

In the non-treated injured group, the capillary-alveolar leakage of FITC-D70 reached a peak within 30 minutes after the OA injury. Thereafter the FITC-D70 leakage decreased gradually until the end of the experiment. Terbutaline infusion, started 90 min after injury, interrupted the recovery with an aggravation in FITC-D70 leakage.

Conclusions

As cardiac index increased with terbutaline infusion, we speculate that terbutaline recruits leaky capillaries and increases FITC-D70 leakage after OA injury. These findings suggest that therapies inducing an increase in cardiac output and a decrease in pulmonary vascular resistances have the potential to heighten the early increase in protein transport from plasma to alveoli within the acutely injured lung.
Antagonistic roles of four SR proteins in the biosynthesis of alternatively spliced tissue factor transcripts in monocytic cells
Authors: Chandradas Sajiv , Deikus Gintaras , Tardos Jonathan G , Bogdanov Vladimir Y
Published: October 2009

Tissue factor profile of human monocytic cells, afforded by alternative splicing, can be greatly influenced by the activity of SR proteins.

Following recruitment to solid tissues, peripheral blood monocytes express a number of proinflammatory molecules including TF, a trigger of coagulation that also promotes cell–cell interactions and tissue remodeling. Monocytes express two forms of TF: flTF, a highly coagulant transmembrane form, and asTF, a highly proangiogenic, soluble TF form. Biosynthesis of the two TF forms occurs via alternative processing of exon 5 during pre-mRNA splicing. Its inclusion results in flTF mRNA and its exclusion, asTF mRNA. We developed a splicing reporter system recently and determined that two spliceosomal constituents, SR proteins ASF/SF2 and SRp55, play a pivotal role in exon 5 inclusion. In this report, we show for the first time that two other SR proteins expressed in human monocytes, SRp40 and SC35, antagonize ASF/SF2 and SRp55 by competing for binding to certain sites in exon 5, thereby promoting TF exon 5 exclusion, an event unique to asTF biosynthesis. We also show that the intron preceding TF exon 5 possesses characteristics rarely found in U2 introns. Our findings indicate that modulation of TF pre-mRNA splicing can be accomplished via modification of SR proteins’ activity, facilitating development of novel therapeutic strategies to modulate the “TF profile” of monocytes/macrophages.
Xenopus δ-catenin is essential in early embryogenesis and is functionally linked to cadherins and small GTPases
Authors: Gu Dongmin , Sater Amy K. , Ji Hong , Cho Kyucheol , Clark Melissa , Stratton Sabrina A. , Barton Michelle C. , Lu Qun , McCrea Pierre D.
Published: October 2009

Catenins of the p120 subclass display an array of intracellular localizations and functions. Although the genetic knockout of mouse δ-catenin results in mild cognitive dysfunction, we found severe effects of its depletion in Xenopus. δ-catenin in Xenopus is transcribed as a full-length mRNA, or as three (or more) alternatively spliced isoforms designated A, B and C. Further structural and functional complexity is suggested by three predicted and alternative translation initiation sites. Transcript analysis suggests that each splice isoform is expressed during embryogenesis, with the B and C transcript levels varying according to developmental stage. Unlike the primarily neural expression of δ-catenin reported in mammals, δ-catenin is detectable in most adult Xenopus tissues, although it is enriched in neural structures. δ-catenin associates with classical cadherins, with crude embryo fractionations further revealing non-plasma-membrane pools that might be involved in cytoplasmic and/or nuclear functions. Depletion of δ-catenin caused gastrulation defects, phenotypes that were further enhanced by co-depletion of the related p120-catenin. Depletion was significantly rescued by titrated p120-catenin expression, suggesting that these catenins have shared roles. Biochemical assays indicated that δ-catenin depletion results in reduced cadherin levels and cell adhesion, as well as perturbation of RhoA and Rac1. Titrated doses of C-cadherin, dominant-negative RhoA or constitutively active Rac1 significantly rescued δ-catenin depletion. Collectively, our experiments indicate that δ-catenin has an essential role in amphibian development, and has functional links to cadherins and Rho-family GTPases.
Carbon capture and storage: The ten year challenge
Authors: Chalmers H , Gibbins J
Published: October 2009

Carbon capture and storage (CCS) could play a significant role in reducing global CO2 emissions. It has the unique characteristic of keeping fossil carbon in the ground by allowing fossil fuels to be used, but with the CO2 produced being safely stored in a geological formation. Initial versions of the key component technologies are at a sufficient level of maturity to build integrated commercial-scale demonstration plants. If CCS is to reach its full potential to contribute to global efforts to mitigate the risk of dangerous climate change, it is urgent that a number of actions begin now in order to be ready for CCS deployment from around 2020 using proven designs that can be built in large numbers. This article discusses some key challenges for CCS, with a focus on development in the next decade, highlighting the potential benefits of a two tranche programme for integrated commercial-scale demonstration to develop proven reference plant designs and reviewing the importance of distinguishing between different classes of CCS according to their ability to significantly reduce CO2 emissions associated with fossil fuel use. It also identifies some ongoing CCS projects and initiatives and examines some possible implications of current policy discussions for technology development.
Parallel mechanisms with decoupled rotation of the moving platform in planar motion
Authors: Gogu G
Published: October 2009

The current article presents a new family of T2R1-type spatial parallel mechanisms (PMs) with decoupled and unlimited rotation of the moving platform in planar motion. The moving platform performs two independent translations (T2) and one independent unlimited rotation (R1) whose axis is perpendicular to the plane of translations. A method is proposed for structural synthesis of T2R1-type PMs based on the theory of linear transformations. The moving platform has unlimited rotational capabilities and is decoupled with respect to translational motion. To the best of the author's knowledge, this article presents for the first time solutions of T2R1-type spatial PMs with decoupled and unlimited rotation of the moving platform in planar motion.
Do Telephones Overcome Geographical Barriers to General Practice Out-Of-Hours Services? Mixed-Methods Study of Parents with Young Children
Authors: Turnbull Joanne , Pope Catherine , Martin David , Lattimer Valerie
Published: October 2009

Objective

To examine if telephones overcome geographical barriers to accessing primary care out-of-hours by parents of young children.

Methods

Mixed methods including quantitative analysis of 5697 calls about children aged 0-4 years, 30 hours of observation at primary care centres, eight interviews with parents and a review of 80 telephone call recordings.

Results

Call rates for children (0-4 years) decreased with increasing distance: the 20% of people who lived furthest from a primary care centre made fewer calls, 570 per 1000 patients/year (95% CI 558 to 582) than the 20% living closest, 652 (95% CI 644 to 661). Overall, call rates decreased with increasing rurality. Qualitative analysis suggested that this geographical variation was linked to familiarity with the system (notably previous contact with health services) and the availability of services, legitimacy of demand (particularly for children) and negotiation about mode of care.

Conclusions

People already disadvantaged by their distance from facilities or socioeconomic circumstances may continue to be at a disadvantage when services are provided by telephone.
A Low-Dimensional Semidefinite Relaxation for the Quadratic Assignment Problem
Authors: Ding Yichuan , Wolkowicz Henry
Published: October 2009

The quadratic assignment problem (QAP) is arguably one of the hardest NP-hard discrete optimization problems. Problems of dimension greater than 25 are still considered to be large scale. Current successful solution techniques use branch-and-bound methods, which rely on obtaining strong and inexpensive bounds. In this paper, we introduce a new semidefinite programming (SDP) relaxation for generating bounds for the QAP in the trace formulation. We apply majorization to obtain a relaxation of the orthogonal similarity set of the quadratic part of the objective function. This exploits the matrix structure of QAP and results in a relaxation with much smaller dimension than other current SDP relaxations. We compare the resulting bounds with several other computationally inexpensive bounds such as the convex quadratic programming relaxation (QPB). We find that our method provides stronger bounds on average and is adaptable for branch-and-bound methods.
The Becton Dickinson FocalPoint GS Imaging System
Authors: Wilbur David C. , Black-Schaffer W. Stephen , Luff Ronald D. , Abraham Kurian P. , Kemper Cynthia , Molina James T. , Tench William D.
Published: October 2009

Location-guided screening in cervical cytology offers a potentially significant advance over routine manual screening. A prospective, 2-armed, masked clinical trial of the BD FocalPoint GS Imaging System using SurePath slides (BD Diagnostics-TriPath, Burlington, NC) compared routine manual screening and quality control rescreening with computer-assisted, field-of-view screening and device-directed quality control rescreening. The results obtained in the 2 arms were compared with adjudicated reference diagnoses for each slide. Sensitivity, specificity, and negative predictive value were calculated for the detection of atypical squamous cells of undetermined significance and greater (ASC-US+), low-grade squamous intraepithelial lesion and greater (LSIL+), and high-grade squamous intraepithelial lesion and greater (HSIL+) groups. We evaluated 12,313 slides. The detection sensitivities for HSIL+ were increased by 19.6% (P < .0001) and for LSIL+ were increased by 9.8% (P < .0001) in the computer-assisted arm, with small statistically significant decreases in specificity. For ASC-US+ sensitivity and specificity, the study arms were not statistically different. Use of this system might be expected to improve accuracy for clinically important entities without increasing equivocal case detection.
Safety of Concomitant Tamoxifen and Warfarin
Authors: Givens Carrie B , Bullock Laura N , Franks Andrea S
Published: October 2009

Objective:

To review the literature regarding the potential interaction between tamoxifen and warfarin.

Data Sources:

A search of MEDLINE from 1948 to August 20, 2009, was performed using the search terms tamoxifen, warfarin, drug interactions, and cytochrome P450 2C9. EMBASE was searched (1980–week 33, 2009), using the search terms tamoxifen and warfarin, for articles limited to use in humans and published in English, then further narrowed to drug interactions. Bibliographic review was conducted but did not reveal any additional references.

Study Selection and Data Extraction:

All sources evaluated were published in English and included original case reports, letters, and medical record or database reviews that described an interaction between warfarin and tamoxifen.

Data Synthesis:

Since tamoxifen therapy and cancer increase the risk of venous thromboembolism, warfarin may be prescribed to these patients. However, product information, primary literature, and tertiary literature describe concomitant use of tamoxifen and warfarin as a contraindication since this may increase the level of anticoagulation and the risk of bleeding complications. Although the exact mechanism of the interaction is unknown, one theory is that tamoxifen inhibits CYP2C9, which metabolizes the S-isomer of warfarin. Five publications were identified including 2 letters, 2 individual case reports, and 2 retrospective reviews (1 of the case reports was included in a medical record review). Collectively, these articles described a total of 31 patients taking warfarin and tamoxifen concomitantly, with 8 patients experiencing bleeding complications.

Conclusions:

Although concomitant use of warfarin and tamoxifen is deemed a contraindication, evidence regarding this potential interaction is limited. Therefore, safety of concomitant use of tamoxifen and warfarin may be similar to that of other drugs that interact with warfarin, requiring consistent and careful monitoring. However, more evidence is needed to warrant the routine use of this combination.
Embedding Multiple Trajectories in Simulated Recurrent Neural Networks in a Self-Organizing Manner
Authors: Liu Jian K. , Buonomano Dean V.
Published: October 2009

Complex neural dynamics produced by the recurrent architecture of neocortical circuits is critical to the cortex's computational power. However, the synaptic learning rules underlying the creation of stable propagation and reproducible neural trajectories within recurrent networks are not understood. Here, we examined synaptic learning rules with the goal of creating recurrent networks in which evoked activity would: (1) propagate throughout the entire network in response to a brief stimulus while avoiding runaway excitation; (2) exhibit spatially and temporally sparse dynamics; and (3) incorporate multiple neural trajectories, i.e., different input patterns should elicit distinct trajectories. We established that an unsupervised learning rule, termed presynaptic-dependent scaling (PSD), can achieve the proposed network dynamics. To quantify the structure of the trained networks, we developed a recurrence index, which revealed that presynaptic-dependent scaling generated a functionally feedforward network when training with a single stimulus. However, training the network with multiple input patterns established that: (1) multiple non-overlapping stable trajectories can be embedded in the network; and (2) the structure of the network became progressively more complex (recurrent) as the number of training patterns increased. In addition, we determined that PSD and spike-timing-dependent plasticity operating in parallel improved the ability of the network to incorporate multiple and less variable trajectories, but also shortened the duration of the neural trajectory. Together, these results establish one of the first learning rules that can embed multiple trajectories, each of which recruits all neurons, within recurrent neural networks in a self-organizing manner.
Nitric Oxide Potentiation of Locomotor Activity in the Spinal Cord of the Lamprey
Authors: Kyriakatos Alexandros , Molinari Micol , Mahmood Riyadh , Grillner Sten , Sillar Keith T. , El Manira Abdeljabbar
Published: October 2009

To understand the intrinsic operation of spinal networks generating locomotion, we need to not only characterize the constituent neurons and their connectivity, but also determine the role of intrinsic modulation in shaping the final motor output. We have focused on the effects of nitric oxide (NO) on the locomotor frequency and the underlying synaptic mechanisms in the lamprey spinal cord. To identify the source of NO, we used NADPH-diaphorase histochemistry and nNOS immunocytochemistry. Gray matter and sensory neurons were positively labeled using both methods. Preparations preincubated with NO synthase inhibitors displayed slower locomotor frequency that increased upon washout of the inhibitors, suggesting that NO is an endogenous neuromodulator in the spinal cord. Application of NO donors increased the locomotor frequency that was blocked by an NO scavenger and partially reduced by an inhibitor of sGC. To analyze the synaptic modulation underlying the NO-induced increase of the locomotor frequency we performed intracellular recordings from motoneurons and interneurons. The NO-induced increase in locomotor frequency was associated with a decrease in the midcycle inhibition and an increase in on-cycle excitation. To determine the site of action of NO, we examined the effect of NO donors on miniature PSCs. NO increased both the frequency and amplitude of mEPSCs while it only decreased the frequency of mIPSCs, suggesting the increased excitation is mediated by both presynaptic and postsynaptic mechanisms, while the decrease in inhibition involves only presynaptic mechanisms. Our results demonstrate a significant role of NO in adult vertebrate motor control which, via modulation of both excitatory and inhibitory transmission, increases the locomotor burst frequency.
FAMILIAL CONGENITAL MUSCULAR DYSTROPHY WITH GONADAL DYSGENESIS
Authors: Bassee H. H.
Published: October 2009

In the medical department, Hammerfest Hospital, seven individuals in one family were observed, suffering from cataract and generalized weakness in the striated musculature. Five of the patients were under ten years of age. The two eldest ones were sister and brother, 22 and 26 years of age, respectively. The woman could hardly walk even with support. She had clinical signs of ovarian agenesis, increased urinary excretion of gonadotrophic hormones, and high tolerance to insulin. The diagnosis was verified by laparotomy demonstrating thin, white, fibrous ovaries and infantile internal genitalia.

The brother could hardly walk, had fairly long extremities, cubitus valgus, and widely separated nipples. The pubic hair presented a feminine appearance and the testicles were infantile and soft. No increase in urinary gonadotrophic hormones were found. The amount of neutral 17-ketosteroids was low and the output of oestrogens increased in urine. The histological examination of testicular tissue showed a thick, fibrous capsule and scanty testicular canals with a few Sertolian cells. Most of the preparation, however, merely consisted of a hyaline substance. In the vascular stroma were seen large heaps of Leydig cells, similar to what is seen in Klinefelter's syndrome.

The ovarian agenesis may either have been caused by a virus infection during early embryonic life or be due to heredity. The latter suggestion is supported by the presentation of two sibs with ovarian agenesis and Klinefelter's syndrome.
SOME OBSERVATIONS ON PREGNANEDIOL EXCRETION DURING THE NORMAL MENSTRUAL CYCLE
Authors: Klopper A.
Published: October 2009

The changes in view on the significance and amount of urinary pregnanediol in the menstrual cycle are reviewed; in particular the effects of the discovery that the adrenals in both sexes normally contribute to the urinary pregnanediol. Pregnanediol excretion during the menstrual cycle was studied by means of a new method of assay (Klopper et al., 1955) and the results applied to present day concepts of the growth and duration of the corpus luteum. The relationship between pregnanediol excretion and ovulation or the onset of menstrual bleeding was studied. A new view is put forward on the influence of age and parity on the production of progesterone by the corpus luteum.
THE INFLUENCE OF ALLOXAN DIABETES, METHYLTHIOURACIL, CORTISONE AND ADRENALINE ON THE UTILIZATION OF GLUCOSE 14C AND L-CYSTINE 35S AND MITOTIC ACTIVITY BY HAIR FOLLICLES IN WHITE MICE
Authors: Davis B. K.
Published: October 2009

Autoradiographs of hair follicles 1, 3, 5 and 8 days after the induction of growth by plucking were prepared from mice injected with 15 μc glucose 14C 5.5 hours before autopsy. It was demonstrated that radioactivity increased principally in the »active« regions of the follicle, namely, the regions engaged in cell proliferation or keratin synthesis. The level of radioactivity in these regions of the follicle increased with maturation.

Alloxan diabetes and cortisone induced a conspicuous depression of glucose 14C absorption during anagen (day-1, 3, 5 follicles) but these effects were markedly reduced in metagen (day-8 follicles). Adrenaline and methylthiouracil (MTU) had no effect on the absorption of glucose 14C at any of the stages of follicle activity observed.

Mitotic counts in follicles from the same animals in which glucose 14C utilization was studied revealed that these endocrine states exerted similar effects on cell proliferation. Alloxan diabetes and cortisone strongly depressed mitotic activity during anagen, but had a relatively weak effect during metagen, in fact cortisone appeared slightly stimulative. Whilst adrenaline and MTU had no apparent influence.

The radioactivity present in follicles representing 2, 4, 6 and 9-day stages of development was assessed by autoradiographic means from mice injected with 1 μc L-cystine 35S 24 hours before autopsy. L-cyst(e)ine 35S was absorbed in large quantities only in day-9 follicles, in which it accumulated mainly in the keratogenous zone.

Absorption of L-cyst(e)ine 35S by metagen (day-9) follicles was unaffected by alloxan diabetes, cortisone, adrenaline and MTU.
ASSAY OF ANDROGENS ADMINISTERED BY INUNCTION TO THE CHICK'S COMB
Authors: Dorfman Ralph I. , Dorfman Adeline S.
Published: October 2009

Androgens dissolved in oil or absolute ethanol may be assayed by inunction to the chick's comb. In an oil solution, the sensitivity is of the order of 10 to 20 μg of testosterone per chick total dose, while absolute ethanol as a solvent permits the detection of about 1 to 2 μg of testosterone. The corn oil vehicle has the higher order of precision with a mean λ of 0.257 as compared to a λ of 0.305 for the absolute ethanol experiment.

When a corn oil vehicle was used, inunction of a 17C = O-Δ4-3C = O compound was more active than the corresponding 17β-OH steroids, but this was not so in the androstane (5α) series. 17α-Methyl compounds tended to be more active than the corresponding 17-desmethyl steroid. The introduction of an 11-oxygen function with or without a 9α-fluoro group severely decreased androgenic activity. Δ16-Dehydroprogesterone was reasonably androgenic in this test using the corn oil vehicle.

When absolute ethanol was used as the solvent, the 17C = O-Δ4-3-C = O compound was slightly more activie than the corresponding 17β-hydroxy steroid, 17α-methyl steroids were more active than the 17α-desmethyl steroids and an 11-oxygen function decreased the activity. Introduction of the 17α-ethyl group in 19-nortestosterone resulted in a compound 270% as active as testosterone, – an unexpected finding since this type of activity enhancement was not found when the 17α-ethyl group was added in the 19-nor-(5α)-dihydrotestosterone series or in Δ5-androstene-3β,17β-diol. Oxygen substitution at carbon 3 in the steroid molecule was not necessary for androgenic activity when the compound was inuncted on the comb in absolute alcohol.

The relationship between the androgenic activity of various compounds when administered by different routes, inunction, subcutaneous injection and by admixture with the food is discussed. No simple interrelationship could be described. However, in some instances it is quite possible that unusually low activities observed when the compounds were administered orally may have been due to poor absorption from the gastrointestinal tract. Compounds in this category include dehydroepiandrosterone, Δ5-androstene-3β,17β-diol and epiandrosterone. All these compounds have a 3β-5α or Δ5-3β-OH grouping.
ZUM WIRKUNGSMECHANISMUS VON AN FETEN ANTIMASKULIN WIRKSAMEN GESTAGENEN
Authors: Junkmann K. , Neumann F.
Published: October 2009

Experiments are described dealing with the mechanism of action of 6-chloro-Δ6-1,2α-methylene-17α-hydroxyprogesterone-acetate with regard to its anti-masculine effect on male rat foetuses, when administered to pregnant rats.

It was shown that a marked direct anti-androgenic effect due to a competitive action on androgen receptors within the target organs, is probably the explanation of the mechanism of action. It was further shown that an oestrogenic effect or an appreciable inhibition of the pituitary gland respectively, can be ruled out as causative factors in the mechanism of action.
ON THE MOLECULAR WEIGHT OF PREGNANT MARE'S SERUM GONADOTROPHIN
Authors: Morris C. J. O. R.
Published: October 2009

The chromatographic behaviour of pregnant mare serum and of a purified preparation of the gonadotrophin from uterine endometrial cup secretion on the cross-linked dextran gel media Sephadex G-100 and G-200 has been examined, and is consistent with a molecular weight greater than the value of 28 000 usually accepted.

The sedimentation coefficient of an active preparation has been determined by sedimentation in a sucrose density gradient and serial bioassay. The value of 3.2 S for SW20 is consistent with current values.

The literature data are shown to be most consistent with a molecular weight of 68 000 for the hormone, and the mechanism of its chromatography on dextran gels is discussed.
EFFECT OF AUDIOGENIC STIMULATION ON GENITAL FUNCTION AND REPRODUCTION.
Authors: Zondek Bernhard , Tamari Isachar
Published: October 2009

Auditory stimuli during the copulation period induce infertility and during gestation blockage of pregnancy. Male and female rats exposed to auditory stimuli for 9 days – prior to mating – become more or less sterile, the fertility decreases to 10-20 per cent, in comparison to 70-80 per cent in the controls. The deleterious effect is a reversible one. Auditory stimuli preceding copulation do not influence the sexual potency, nor do the females refuse the males. The spermatogenic process proceeds in an entirely normal fashion and in the ovaries no anatomical changes could be found to explain the infertility.
INCIDENCE AND RATE OF APPEARANCE AND DISAPPEARANCE OF ANTIGONADOTROPHIN IN THE BLOOD OF PATIENTS TREATED WITH PREGNANT MARES' SERUM GONADOTROPHIN
Authors: Østergaard Erling
Published: October 2009

Thirty-eight patients with amenorrhoea were treated with repeated series of injections of pregnant mares' serum gonadotrophin + human chorionic gonadotrophin. Each course consisted of 5 injections of 1500 IU or 3000 IU of serum gonadotrophin, Antex®, followed by 3 injections of 1500 IU or 3000 IU of chorionic gonadotrophin, Physex®, If required, this treatment was repeated at a few months' intervals, in some cases up to 5 times. After each course, the blood was studied for the presence of antigonadotrophin to Antex. Blood specimens were drawn in all cases 21 days after the last injection of Antex. Antigonadotrophin was found to be present in one out of 15 patients after the 1st course, in 8 out of 20 after the 2nd course, in 13 of 16 after the 3rd, and in 6 of 6 patients after the 4th and 5th courses.

Progonadotrophic activity was demonstrated in the blood of 6 patients after the 1st course, in 4 after the 2nd course, and in one on the 10th day after the 3rd course.

In 6 cases blood samples were obtained also immediately before, during and immediately after the treatment. Three showed, during the 3rd, 4th and 5th course respectively, antigonadotrophin in the blood even before the last injection of Antex. These courses were ineffective, and no patient got menstrual bleeding as a result of the 4th or 5th course.

Some patients developed bleeding after the 3rd treatment, although antigonadotrophin was demonstrated in the blood on the 21st day. In these cases the antigonadotrophin presumably did not form until the injections of Antex had exerted their effect.

The antigonadotrophin occurring during these therapeutic courses inactivates only serum gonadotrophin and limits effective treatment by this gonadotrophin to about 4 weeks in continuous therapy and to 3 of the brief, intensive courses employed in the present series.

Apart from this, the formation of this antigonadotrophin did not have harmful consequences. It disappears from the blood within a period of a few months, occasionally up to about a year, and it does not prevent subsequent treatment with human pituitary gonadotrophin from being effective.
EFFECT OF CASTRATION AND TESTOSTERONE ON PROTEIN BIOSYNTHESIS IN GUINEA PIG TISSUE PREPARATIONS
Authors: Kochakian Charles D.
Published: October 2009

Castration and testosterone administration had no effect on the rate of incorporation of leucine-1-14C into the S 12 000 × g fraction of guinea pig kidneys. The protein biosynthetic activity of the homogenates of the seminal vesicles, however, was greatly and that of the prostate slightly reduced by castration. The administration of testosterone to castrated guinea pigs produced within four days a maximum increase in the rate of leucine incorporation of approximately 500 per cent in the seminal vesicles and about 80 per cent in the prostate. The maximum effect was maintained for at least 23 days under testosterone stimulation. Nine other amino acids gave responses which varied from equal to that of leucine-1-14C to no response. The effect of testosterone was evident in both the supernatant fraction and the sediment after centrifugation at 12 000 × g for 10 minutes of the seminal vesicle homogenate but only the supernatant fraction of the prostate. The reaction in both tissues of control and testosterone treated animals was almost completely dependent on ATP and a generating system. Omission of GTP from the reaction mixture produced only a partial decrease in the incorporating activity of both tissues but without an effect on the testosterone response. The addition of chloramphenicol to the enzyme system had no effect but puromycin almost completely inhibited the amino acid incorporating activity of the tissues of both castrated and androgen treated guinea pigs.
SPECTRAL RESOLUTION OF LOW-FREQUENCY, SMALL-AMPLITUDE RHYTHMS IN EXCRETED 17-KETOSTEROIDS; PROBABLE ANDROGEN-INDUCED CIRCASEPTAN DESYNCHRONIZATION
Authors: Halberg Franz , Engeli Max , Hamburger Christian , Hillman Dewayne
Published: October 2009

The 17-ketosteroid excretion of a healthy human male is characterized by rhythms with a frequency of one cycle in a) about one week; b) about twenty days (± 3 days); c) about one month, and d) about one year. The terms circaseptan, circavigintan, circatrigintan and circannual are considered as names for these rhythms with a low frequency and a small amplitude. These rhythms, among others, can be resolved as statistically significant components in the frequency domain by so-called least squares spectra, prepared by an electronic computer program. The rhythms then stand out above the general level of the spectrum, as components reproducible during an observation span of over 15 years. Certain displays of the amplitude and phase of a rhythm computed and plotted automatically by the electronic computer also are introduced and illustrated. These techniques quantify objectively the external and internal timing of a rhythm and/or changes of this timing.

The crest-time of the seven-day synchronized circaseptan rhythm in 17-ketosteroid excretion and a weekly crest in urine volume are displayed, on the one hand, in a polar amplitude-phase plot. On the other hand, these aspects of physiologic timing are also scrutinized as a function of time in plots on rectangular coordinates involving the fit of a precise frequency, established independently as a characteristic of the series analyzed.

For a span covering almost a decade, the circaseptan rhythm in 17-ketosteroid excretion is shown to be clearly synchronized with the seven-day cyclic alternation of professional and other activity of the (one) subject investigated. Moreover, in the face of a continuing precise seven-day routine of living, this circaseptan rhythm can be demonstrated to freerun thereafter during a three year span, presumably as a result of long continued frequent testosterone administration.

The computational methods used and, in particular, the displays here introduced are more broadly applicable, inter alia, in endocrinology, to the detection of rhythms and to the objective quantification of their parameters, including the internal and external timing.
FREE AND CONJUGATED ESTROGENS IN BLOOD AND URINE BEFORE AND DURING PARTURITION IN NORMAL HUMAN PREGNANCY
Authors: Smith Olive Watkins
Published: October 2009

The concentrations of the free (F), glucosiduronate (G), sulfoglucosiduronate (S:G) and sulfate (S) forms of estriol (E3), estrone (E1) and estradiol (E2) in the plasma and urine of 5 normally pregnant women have been measured before and during parturition.

Of the total plasma E1 + E2 + E3, 25–80% was E3 with 15–60% of this accountable to G, 15–40% to S and 7–42% to S:G, these being the major forms of circulating E3. Five to 60% of the total was E1, with 50–90% of this accountable to S, the major circulating form of E1. Five to 15% of the total was E2 with 70–95% of this accountable to F, the major circulating form of E2. These wide ranges of distribution were due to marked changes in plasma concentrations which followed consistent patterns for each constituent before and during labor. Just before labor there was a decrease in the concentration of all of the major forms. During labor the amount of circulating E3-G and E3-S:G continued to decrease while E3-S, E1-S and E2-F increased.

Plasma and urinary levels did not run parallel. Of the total urinary E1 + E2 + E3, 75–97% was E3 with 85–97% of this accountable to G and 2–13% to S:G + S; 2–21% of the total was E1 with 1.5–7.5% of this accountable to S; and 1–4% of the total was E2 with less than 2% of this accountable to F. Thus there was a considerably higher concentration of E3-G in the urine than in the plasma; and 90–98% of E1 and E2 were excreted as G, whereas only trace amounts of these 2 hormones circulated as G.

Urine to plasma ratios indicated that the glucosiduronates of all estrogens were secreted by the kidney tubule while the sulfurylated and free forms were reabsorbed. Both renal mechanisms were accelerated before and during labor. They failed to fully explain the preparturition decreases in plasma concentrations.