tbuckley/cabot-search huggingface dataset:
Secretion of Unconjugated Androgens and Estrogens by the Normal and Abnormal Human Testis before and after Human Chorionic Gonadotropin
Authors: R. L. Weinstein, R. P. Kelch, M. R. Jenner, S. L. Kaplan, M. M. Grumbach
Journal: Journal of Clinical Investigation (1974)

The secretion of androgens and estrogens by normal and abnormal testes was compared by determining the concentrations of dehydroepiandrosterone (DHEA), androstenedione (Delta(4)A), testosterone (T), estrone (E(1)), and 17beta-estradiol (E(2)) in peripheral and spermatic venous plasma samples from 14 normal men and 5 men with unilateral testicular atrophy. Four normal men and one patient with unilateral atrophy of the testis were given human chorionic gonadotropin (HCG) before surgery. Plasma estrogens were determined by radioimmunoassay; plasma androgens were measured by the double-isotope dilution derivative technique. Peripheral concentrations of these steroids before and after HCG were similar in both the normal men and the patients with unilateral testicular atrophy. In normal men, the mean +/-SE spermatic venous concentrations were DHEA, 73.1+/-11.7 ng/ml; Delta(4)A, 30.7+/-7.9 ng/ml; T, 751+/-114 ng/ml; E(1), 306+/-55 pg/ml; and E(2), 1298+/-216 pg/ml. Three of four subjects with unilateral testicular atrophy had greatly diminished spermatic venous levels of androgens and estrogens. HCG treatment increased the testicular secretion of DHEA and T fivefold, Delta(4)A threefold, E(1) sixfold, and E(2) eightfold in normal men. In the single subject with an atrophic testis who received HCG, the spermatic venous concentrations of androgens and estrogens were much less than in normal men similarly treated. We conclude that: (a) E(1) is secreted by the human testis, but testicular secretion of E(1) accounts for less than 5% of E(1) production in normal men; (b) HCG stimulation produces increases in spermatic venous estrogens equal to or greater than the changes in androgens, including testosterone; and (c) strikingly decreased secretion of androgen and estrogen by unilateral atrophic human tests cannot be appreciated by analyses of peripheral steroid concentrations.
CHLORALAMID AS A HYPNOTIC FOR THE INSANE
Authors: William Mabon
Journal: American Journal of Psychiatry (1890)

The drug was administered, in doses of from twenty to sixty grains, one hundred and thirty times, and the results are summarized as follows: Twenty grains were given twice and they produced an average sleep of three and three-quarter hours. Thirty grains administered fifty-one times averaged five hours' sleep. Seventy-four doses of forty-five grains procured sleep which averaged four and two-fifths hours. Average of sixty grain doses given three times, was three and five-sixths hours. General average was four and three-fifths hours. In the successful cases thirty grain doses seemed to give the most satisfactory sleep. The time required to induce sleep varied from fifteen minutes to five hours, and in character it was with few exceptions light and restless. In case No. III nausea and inco-ordination followed the administration of forty-five grains. Once (Case XIII) vomiting was produced. In Case XIV some confusion and inco-ordination were noticed and in Case XVI patient complained of vertigo. Finally. These limited observations seem to the writer to indicate that in this class of cases we have in sulfonal and chloral better means for procuring quiet and restful sleep than is vouchsafed by chloralamid.
Neurite outgrowth and synaptophysin expression of postnatal CNS neurons on GaP nanowire arrays in long-term retinal cell culture
Authors: Gaëlle Piret, Maria-Thereza Perez, Christelle N. Prinz
Journal: Biomaterials (2012)

We have established long-term cultures of postnatal retinal cells on arrays of gallium phosphide nanowires of different geometries. Rod and cone photoreceptors, ganglion cells and bipolar cells survived on the substrates for at least 18 days in vitro. Glial cells were also observed, but these did not overgrow the neuronal population. On nanowires, neurons extended numerous long and branched neurites that expressed the synaptic vesicle marker synaptophysin. The longest nanowires (4 μm long) allowed a greater attachment and neurite elongation and our analysis suggests that the length of the nanowire per se and/or the adsorption of biomolecules on the nanowires may have been important factors regulating the observed cell behavior. The study thus shows that CNS neurons are amenable to gallium phosphide nanowires, probably as they create conditions that more closely resemble those encountered in the in vivo environment. These findings suggest that gallium phosphide nanowires may be considered as a material of interest when improving existing or designing the next generation of implantable devices. The features of gallium phosphide nanowires can be precisely controlled, making them suitable for this purpose.
Increased Expression of Ca <sup>2+</sup> -Sensitive K <sup>+</sup> Channels in the Cerebral Microcirculation of Genetically Hypertensive Rats
Authors: Yanping Liu, Antal G. Hudetz, Hans-Guenther Knaus, Nancy J. Rusch
Journal: Circulation Research (1998)

Abstract —The Ca 2+ -sensitive K + channel (K Ca channel) plays a key role in buffering pressure-induced constriction of small cerebral arteries. An amplified current through this channel has been reported in vascular smooth muscle cells obtained from hypertensive animals, implying that the expression or properties of K Ca channels may be regulated by in vivo blood pressure levels. In this study, we investigated this hypothesis and its functional relevance by comparing the properties, expression levels, and physiological role of K Ca channels in cerebral resistance arteries from normotensive and genetically hypertensive rats. Whole-cell patch-clamp experiments revealed a 4.7-fold higher density of iberiotoxin-sensitive K Ca channel current at physiological membrane potentials in spontaneously hypertensive rat (SHR) compared with Wistar-Kyoto (WKY) rat cerebrovascular smooth muscle cells (n=18 and 21, respectively). However, additional single-channel analysis in detached patches showed similar levels of unitary conductance, voltage, and Ca 2+ sensitivity in K Ca channels from WKY and from SHR membranes. In contrast, Western analysis using an antibody directed against the K Ca channel α-subunit revealed a 4.1-fold increase in the corresponding 125-kD immunoreactive signal in cerebrovascular membranes from SHR compared with WKY rats. The functional impact of this enhanced K Ca channel expression was assessed in SHR and WKY rat pial arterioles, which were monitored by intravital microscopy through in situ cranial windows. Progressive pharmacological block of K Ca channels by iberiotoxin (0.1 to 100 nmol/L) dose-dependently constricted pial arterioles from SHR and WKY rats (n=6 to 8). The arterioles in SHR constricted 2- to 4-fold more intensely, and vasospasm occurred in some vessels. These data provide the first direct evidence that elevated levels of in situ blood pressure induce K Ca channel expression in cerebrovascular smooth muscle membranes. This homeostatic mechanism may critically regulate the resting tone of cerebral arterioles during chronic hypertension. Furthermore, the overexpression of distinct K + channel types during specific cardiovascular pathologies may provide for the upregulation of novel disease-specific membrane targets for vasodilator therapies.
Morphological alterations of epidermal melanocytes in photoageing: an ultrastructural and cytomorphometric study
Authors: None Toyoda, None Morohashi
Journal: British Journal of Dermatology (1998)

To examine pathological changes of melanocytes in photodamaged skin, we performed a comparative cytomorphometric analysis and a qualitative observation of melanocytes from sun-exposed and sun-protected facial skin at the electron microscopic level. The characteristic ultrastructural features of melanocytes in photodamaged skin included a statistically significant increase in their number, a marked nuclear heterogeneity, signs of cell activation, close apposition to photodamaged degenerate keratinocytes, degenerative changes represented by large intracytoplasmic vacuoles, and frequent direct contacts with Langerhans cells. Cytomorphometric analysis revealed significant decreases in cell and nuclear sizes, increases in cell and nuclear perimeters accompanied by irregular contours, and higher degrees of nuclear ellipticity in sun-exposed melanocytes. This study demonstrates that there are remarkable differences in the morphology of melanocytes between photoaged and intrinsically aged facial skin, and supports the concept that photoageing processes contribute to cytological alterations in melanocytes.
Estrogen-Responsive Finger Protein as a New Potential Biomarker for Breast Cancer
Authors: Takashi Suzuki, Tomohiko Urano, Tohru Tsukui, Kuniko Horie-Inoue, Takuya Moriya, Takanori Ishida, Masami Muramatsu, Yasuyoshi Ouchi, Hironobu Sasano, Satoshi Inoue
Journal: Clinical Cancer Research (2005)

Abstract Purpose: Estrogen-responsive finger protein (Efp) is a member of RING finger-B box-Coiled Coil family and is also a downstream target of estrogen receptor α. Previously, Efp was shown to mediate estrogen-induced cell growth, which suggests possible involvement in the development of human breast carcinomas. In this study, we examined expression of Efp in breast carcinoma tissues and correlated these findings with various clinicopathologic variables. Experimental Design: Thirty frozen specimens of breast carcinomas were used for immunohistochemistry and laser capture microdissection/real-time PCR of Efp. Immunohistochemistry for Efp was also done in 151 breast carcinoma specimens fixed with formalin and embedded in paraffin wax. Results: Efp immunoreactivity was detected in breast carcinoma cells and was significantly associated with the mRNA level (n = 30). Efp immunoreactivity was positively associated with lymph node status or estrogen receptor α status and negatively correlated with histologic grade or 14-3-3σ immunoreactivity (n = 151). Moreover, Efp immunoreactivity was significantly correlated with poor prognosis of breast cancer patients, and multivariate analyses of disease-free survival and overall survival for 151 breast cancer patients showed that Efp immunoreactivity was the independent marker. Conclusions: Our data suggest that Efp immunoreactivity is a significant prognostic factor in breast cancer patients. These findings may account for an oncogenic role of Efp in the tumor progression of breast carcinoma.
Coronary Heart Disease: Overweight and Obesity as Risk Factors
Authors: Ancel Keys, Christ Aravanis, Henry Blackburn, F. S. P. Van Buchem, Ratko Buzina, B. S. Djordjevic, Flaminio Fidanza, Martti J. Karvonen, Alessandro Menotti, Vittorio Puddu, Henry L. Taylor
Journal: Annals of Internal Medicine (1972)

The relationship of relative weight and of skinfold thickness to the 5-year incidence (632 cases) of coronary heart disease was examined in men aged 40 through 59 years at entry to the study: 2442 U.S. railroad men; 2439 men in northern Europe; and 6519 men in southern Europe. Disregarding other variables, an excessive incidence of coronary heart disease was associated with overweight and obesity in the U.S. and southern Europe but not in northern Europe. There were 163 cases of death or definite infarction; this incidence was not significantly related to any of the measures of relative weight or obesity in any sample. Multivariate analysis of the data showed that no measure of relative weight or obesity made a significant contribution to future coronary heart disease, when the factors of age, blood pressure, serum cholesterol, and smoking were comparable. Essentially identical results were found with different multivariate methods.
Regulation of Sympathetic Nerve Activity in Heart Failure
Authors: Jun-Li Liu, Irving H. Zucker
Journal: Circulation Research (1999)

The mechanisms by which sympathetic function is augmented in chronic heart failure (CHF) are not well understood. A previous study from this laboratory (Circ Res. 1998;82:496-502) indicated that blockade of nitric oxide (NO) synthesis resulted in only an increase in renal sympathetic nerve activity (RSNA) when plasma angiotensin II (Ang II) levels were elevated. The present study was undertaken to determine if NO reduces RSNA in rabbits with CHF when Ang II receptors are blocked. Twenty-four New Zealand White rabbits were instrumented with cardiac dimension crystals, a left ventricular pacing lead, and a pacemaker. After pacing at 360 to 380 bpm for approximately 3 weeks, a renal sympathetic nerve electrode and arterial and venous catheters were implanted. Studies were carried out in the conscious state 3 to 7 days after electrode implantation. The effects of a 1-hour infusion of sodium nitroprusside (SNP; 3 microgram . kg-1. min-1) on RSNA and mean arterial pressure (MAP) were determined before and after Ang II blockade with losartan (5 mg/kg) in normal and CHF rabbits. Changes in MAP were readjusted to normal with phenylephrine. Before losartan, SNP evoked a decrease in MAP and an increase in RSNA in both groups that was baroreflex-mediated, because both MAP and RSNA returned to control when phenylephrine was administered. In the normal group, losartan plus SNP caused a reduction in MAP and an increase in RSNA that was 152.6+/-9.8% of control. Phenylephrine returned both MAP and RSNA back to the control levels. However, in the CHF group, losartan plus SNP evoked a smaller change in RSNA for equivalent changes in MAP (117.1+/-4.1% of control). On returning MAP to the control level with phenylephrine, RSNA was reduced to 65.2+/-2.9% of control (P<0. 0001). These data suggest that endogenous Ang II contributes to the sympathoexcitation in the CHF state and that blockade of Ang II receptors plus providing an exogenous source of NO reduces RSNA below the elevated baseline levels. We conclude that both a loss of NO and an increase in Ang II are necessary for sustained increases in sympathetic nerve activity in the CHF state.
Mechanisms and Molecules that Control Growth Cone Guidance
Authors: C S Goodman
Journal: Annual Review of Neuroscience (1996)

Neuronal growth cones traverse long distances along appropriate pathways to find their correct targets. This review presents an overview of the mechanisms and molecules that control these events. Secreted and cell surface ligands in the growth cone's environment bind to receptors on the growth cone's surface, trigger second-messenger signals, and lead to appropriate steering decisions. Growth cones appear to be guided by at least four different mechanisms: contact-mediated attraction, chemoattraction, contact-mediated repulsion, and chemorepulsion. These mechanisms are mediated by many different families of guidance molecules, including neural cell adhesion molecules of the immunoglobulin superfamily, netrins, and semaphorins, all of which appear to be highly conserved from worms and fruitflies to mice and humans. We are just beginning to gain insights into the functions of these and other molecules in the developing organism by the use of genetic analysis.
Quantification of hydrogen peroxide generation by Granuflex™ (DuoDERM™) Hydrocolloid Granules and its constituents (gelatin, sodium carboxymethylcellulose, and pectin)
Authors: R.J. SCHMIDT, L.Y. CHUNG, T.D. TURNER
Journal: British Journal of Dermatology (1993)

The hydrogen peroxide generating capacity of Granuflex Hydrocolloid Granules and its constituents (porcine gelatin, sodium carboxymethylcellulose and pectin) was examined using the scopoletin-horseradish peroxidase assay in the presence and absence of catalase. Oxygen purging reduced the formation of hydrogen peroxide by 77-96%. The total concentrations of hydrogen peroxide detected were 1.9 x 10(-6), 1.2 x 10(-6) and 2.3 x 10(-6) mol/l for Granuflex, pectin and gelatin (using 0.5% w/v), respectively, after 48 h incubation in a phosphate buffer, pH 7.4, at 37 degrees C. No hydrogen peroxide was formed by sodium carboxymethylcellulose. The results indicate that hydrogen peroxide generation by Granuflex may be ascribed to its gelatin and pectin components, but not to the sodium carboxymethylcellulose. The release of low levels of hydrogen peroxide into the wound environment could conceivably contribute both to the inflammatory phase and to fibroblast proliferation, and hence to the granulation phase of wound healing.
Definitive Results of a Phase III Adjuvant Trial Comparing Three Chemotherapy Regimens in Women With Operable, Node-Positive Breast Cancer: The NSABP B-38 Trial
Authors: Sandra M. Swain, Gong Tang, Charles E. Geyer, Priya Rastogi, James N. Atkins, Paul P. Donnellan, Louis Fehrenbacher, Catherine A. Azar, André Robidoux, Jonathan A. Polikoff, Adam M. Brufsky, David D. Biggs, Edward A. Levine, John L. Zapas, Louise Provencher, Donald W. Northfelt, Soonmyung Paik, Joseph P. Costantino, Eleftherios P. Mamounas, Norman Wolmark
Journal: Journal of Clinical Oncology (2013)

Anthracycline- and taxane-based three-drug chemotherapy regimens have proven benefit as adjuvant therapy for early-stage breast cancer. This trial (NSABP B-38; Combination Chemotherapy in Treating Women Who Have Undergone Surgery for Node-Positive Breast Cancer) asked whether the incorporation of a fourth drug could improve outcomes relative to two standard regimens and provided a direct comparison of those two regimens.We randomly assigned 4,894 women with node-positive early-stage breast cancer to six cycles of docetaxel, doxorubicin, and cyclophosphamide (TAC), four cycles of dose-dense (DD) doxorubicin and cyclophosphamide followed by four cycles of DD paclitaxel (P; DD AC→P), or DD AC→P with four cycles of gemcitabine (G) added to the DD paclitaxel (DD AC→PG). Primary granulocyte colony-stimulating factor support was required; erythropoiesis-stimulating agents (ESAs) were used at the investigator's discretion.There were no significant differences in 5-year disease-free survival (DFS) between DD AC→PG and DD AC→P (80.6% v 82.2%; HR, 1.07; P = .41), between DD AC→PG and TAC (80.6% v 80.1%; HR, 0.93; P = .39), in 5-year overall survival (OS) between DD AC→PG and DD AC→P (90.8% v 89.1%; HR, 0.85; P = .13), between DD AC→PG and TAC (90.8% v 89.6%; HR, 0.86; P = .17), or between DD AC→P versus TAC for DFS (HR, 0.87; P = .07) and OS (HR, 1.01; P = .96). Grade 3 to 4 toxicities for TAC, DD AC→P, and DD AC→PG, respectively, were febrile neutropenia (9%, 3%, 3%; P < .001), sensory neuropathy (< 1%, 7%, 6%; P < .001), and diarrhea (7%, 2%, 2%; P < .001). Exploratory analyses for ESAs showed no association with DFS events (HR, 1.02; P = .95).Adding G to DD AC→P did not improve outcomes. No significant differences in efficacy were identified between DD AC→P and TAC, although toxicity profiles differed.
Recurrence rates in localized scleroderma (morphoea)
Authors: A. Kreuter, N. Hunzelmann
Journal: British Journal of Dermatology (2015)

ORIGINAL ARTICLE, p 722 Localized scleroderma (LoS), also called morphoea, denotes a heterogeneous spectrum of sclerotic autoimmune diseases that affect primarily the skin, but might also involve adjacent structures such as the fat tissue, fascia, muscle and bone. Internal organs are not affected in LoS, and there is no transition to systemic sclerosis. Over the last few decades we have gained considerable insights into the pathogenetic background of LoS.1 Moreover, well‐performed clinical studies have been conducted, and have substantially influenced our treatment strategies for the disease.2 Although no universally accepted classification exists, LoS is usually divided into five main groups (limited, generalized, linear, deep and mixed), which can be further subdivided into certain subtypes.3 4 Altogether, our knowledge of LoS has significantly increased in recent years. However, only limited data are currently available on the long‐term clinical course of the disease and associated risk factors. In this issue of BJD, Mertens et al.5 significantly contribute to closing our knowledge gap on the clinical course of LoS. A retrospective analysis was performed on 344 patients with adult‐ or juvenile‐onset LoS diagnosed and treated at the Radboud University Medical Center, the Netherlands, between 1990 and 2013. About one‐quarter of the patients experienced a relapse of disease within the study period. Univariate analysis demonstrated that the age at onset of disease was a risk factor for recurrent disease; relapses occurred significantly more often in paediatric (27%) than in adult (17%) LoS (P = 0·037). Moreover, disease subtype was another risk factor; 36% of patients with linear LoS of the limbs (either solitary or as part of the mixed subtype of LoS) experienced a relapse, whereas recurrences in the other subtypes occurred less frequently (17%) (P < 0·01). The two most frequent subtypes in adults, the plaque type and generalized LoS, had recurrence rates of 16% and 25%, respectively. Importantly, this study also showed that disease relapses can occur after years of quiescent disease; the median time between disease remission and first recurrence was 26 months in juvenile and 27 months in adult LoS.
Assessing Regimen Adherence of Adolescents With Type 1 Diabetes
Authors: Ronald J. Iannotti, Tonja R. Nansel, Stefan Schneider, Denise L. Haynie, Bruce Simons-Morton, Douglas O. Sobel, Linda Zeitzoff, Leslie P. Plotnick, Loretta Clark
Journal: Diabetes Care (2006)

The purpose of this study is to evaluate two updated measures of diabetes regimen adherence. The Diabetes Self-Management Profile (DSMP) is a widely used, structured interview. Limitations include a substantial interviewer and respondent time burden and the need for well-trained interviewers to use appropriate prompts and score the open-ended responses. The Diabetes Behavior Rating Scale (DBRS) is a self-administered, fixed-choice survey.Both measures were administered to 146 youth with type 1 diabetes (aged 11-18 years) and their parents. Items were added to the DBRS to allow for both flexible and conventional regimens, and the DSMP was modified to use standardized wording across items, accommodate flexible regimens, and permit administration by nonmedical interviewers.Both measures had good evidence of internal consistency (for the DSMP: parent 0.75 and youth 0.70; for the DBRS: parent 0.84 and youth 0.84). Scores on the DSMP and the DBRS were significantly related (r = 0.72 for parents and 0.74 for youth). There was moderate agreement between parent and youth (DSMP, r = 0.51; DBRS, r = 0.48). The measures were correlated with HbA1c for both parent (DSMP, r = -0.35; DBRS, r = -0.35) and youth (DSMP, r = -0.36; DBRS, r = -0.34) reports.Both measures exhibit good psychometric properties and good criterion validity but varied in terms of respondent and interviewer burden, issues that should be considered in selecting assessment procedures.