tbuckley/cabot-search huggingface dataset:
TELANGIECTATIC CHANGES IN SCLERODERMA
Authors: F. Kogoj
Journal: British Journal of Dermatology (1967)

Journal Article TELANGIECTATIC CHANGES IN SCLERODERMA Get access F. KOGOJ F. KOGOJ Department of Dermatology, Medical Faculty, Zagreb, Yugoslavia Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 79, Issue 8-9, 1 August 1967, Pages 443–448, https://doi.org/10.1111/j.1365-2133.1967.tb11530.x Published: 01 August 1967
Ablation of the Leptin Receptor in the Hypothalamic Arcuate Nucleus Abrogates Leptin-Induced Sympathetic Activation
Authors: Shannon M. Harlan, Donald A. Morgan, Khristofor Agassandian, Deng-Fu Guo, Martin D. Cassell, Curt D. Sigmund, Allyn L. Mark, Kamal Rahmouni
Journal: Circulation Research (2011)

The hypothalamic arcuate nucleus (ARC) is considered a major site for leptin signaling that regulates several physiological processes.To test the hypothesis that leptin receptor in the ARC is required to mediate leptin-induced sympathetic activation.First, we used the ROSA Cre-reporter mice to establish the feasibility of driving Cre expression in the ARC in a controlled manner with bilateral microinjection of adenovirus-expressing Cre-recombinase (Ad-Cre). Ad-Cre microinjection into the ARC of ObR(flox/flox) mice robustly reduced ObR expression and leptin-induced Stat3 activation in the ARC but not in the adjacent nuclei, confirming the efficacy and selectivity of the ARC deletion of ObR. Critically, deletion of ObR in the ARC attenuated brown adipose tissue and renal sympathetic nerve responses to leptin. We also examined whether ObR in the ARC is required for the preserved leptin-induced increase in renal sympathetic activity in dietary obesity. We found that deletion of ARC ObR abrogated leptin-induced increases in renal sympathetic discharge and resolved arterial pressure elevation in diet-induced obese ObR(flox/flox) mice.These data demonstrate a critical role for ObR in the ARC in mediating the sympathetic nerve responses to leptin and in the adverse sympathoexcitatory effects of leptin in obesity.
Mutations in SIP1, encoding Smad interacting protein-1, cause a form of Hirschsprung disease
Authors: Nobuaki Wakamatsu, Yasukazu Yamada, Kenichiro Yamada, Takao Ono, Noriko Nomura, Hiroko Taniguchi, Hiroshi Kitoh, Norihiro Mutoh, Tsutomu Yamanaka, Kyosuke Mushiake, Kanefusa Kato, Shin-ichi Sonta, Masahiro Nagaya
Journal: Nature Genetics (2001)
Small intestinal mucosal abnormalities in relatives of patients with dermatitis herpetiformis
Authors: J. Marks, D. Birkett, S. Shuster, D. F. Roberts
Journal: Gut (1970)

Jejunal biopsy has been carried out in 19 relatives of patients with dermatitis herpetiformis and stereomicroscopic abnormalities have been found in seven. The majority of the relatives in whom these abnormalities were found had no bowel symptoms: one had the rash of dermatitis herpetiformis. All but one of the propositi of the relatives in whom were found small intestinal mucosal abnormalities themselves had the coeliac syndrome. It is concluded that a genetic factor is involved in the production of the enteropathy of dermatitis herpetiformis as in other forms of the coeliac syndrome.
Reduced pulmonary metabolism of endothelin-1 in canine tachycardia-induced heart failure
Authors: Jocelyn Dupuis, Gordon W Moe, Peter Cernacek
Journal: Cardiovascular Research (1998)

Objectives: Plasma endothelin-1 (ET-1) increases in congestive heart failure (CHF). The pulmonary vascular bed could contribute to this increase through a reduced clearance. We evaluated the effect of tachycardia-induced CHF on pulmonary ET-1 kinetics. To discern between changes due to variations in pulmonary hemodynamics from true alterations of endothelial cell functions, we quantified ET-1 kinetics in isolated rat lungs under variable pressure and flow-rate conditions. Methods and Results: Indicator-dilution studies were performed in anesthetized dogs (n=14) before and 3 weeks after rapid ventricular pacing and in isolated lungs from healthy rats (n=4). In isolated lungs, graded increases in perfusion rate from 5–25 ml/min caused gradual reductions in ET-1 extraction from 60±1.5% to 17±4.9% (mean±S.D.). The capacity to clear ET-1 from the circulation, as computed from the permeability–surface area product (PS), however did not vary over this range of flows. CHF increased plasma ET-1 (11.2±11.4 vs. 5.2±1.6 fmol/ml, p<0.01), did not affect pulmonary ET-1 extraction (29.4±12.5% vs. 29.9±12.9%), but decreased the PS (8.3±5.4 cm3/s vs. 14.4±9.9 cm3/s, p=0.038). Contrary to the invariability of the PS in normal isolated rat lungs, CHF was associated with a positive relationship between the PS and pulmonary plasma flow (r=0.65, p<0.01). ET-1 binding studies in lung tissues showed no significant variations in ETA and ETB receptors densities but revealed a threefold decrease in binding affinity (p<0.01) that may explain the reduced clearance. Conclusion: CHF causes a reduction of pulmonary ET-1 clearance that likely contributes to the increased circulating ET-1 levels and reflects pulmonary metabolic dysfunction associated with this condition.
THE IMPACT OF RENAL INSUFFICIENCY ON 2-YEAR OUTCOMES FOLLOWING PCI OR CABG IN THE SYNTAX TRIAL
Authors: David R. Holmes, Friedrich W. Mohr, Patrick W. Serruys, Michael J. Mack, Paul Vermeersch, Philip Van Cauwelaert, Kari Virtanen, Ari Lasse Harjula, Katrin Leadley, Keith D. Dawkins
Journal: Journal of the American College of Cardiology (2010)
Ventilatory Control and Airway Anatomy in Obstructive Sleep Apnea
Authors: Andrew Wellman, Amy S. Jordan, Atul Malhotra, Robert B. Fogel, Eliot S. Katz, Karen Schory, Jill K. Edwards, David P. White
Journal: American Journal of Respiratory and Critical Care Medicine (2004)

Ventilatory instability may play an important role in the pathogenesis of obstructive sleep apnea. We hypothesized that the influence of ventilatory instability in this disorder would vary depending on the underlying collapsibility of the upper airway. To test this hypothesis, we correlated loop gain with apnea–hypopnea index during supine, nonrapid eye movement sleep in three groups of patients with obstructive sleep apnea based on pharyngeal closing pressure: negative pressure group (pharyngeal closing pressure less than –1 cm H2O), atmospheric pressure group (between –1 and +1 cm H2O), and positive pressure group (greater than +1 cm H2O). Loop gain was measured by sequentially increasing proportional assist ventilation until periodic breathing developed, which occurred in 24 of 25 subjects. Mean loop gain for all three groups was 0.37 ± 0.11. A significant correlation was found between loop gain and apnea–hypopnea index in the atmospheric group only (r = 0.88, p = 0.0016). We conclude that loop gain has a substantial impact on apnea severity in certain patients with sleep apnea, particularly those with a pharyngeal closing pressure near atmospheric.
Otic Lesions and Congenital Hypothyroidism in the Developing Chick*
Authors: Gerald J. Bargman, Lytt I. Gardner
Journal: Journal of Clinical Investigation (1967)

In an effort to elucidate the relation, if any, between thyroid abnormality and congenital deafness in Pendred's syndrome, an experiment was designed to study the effects of hypothyroidism on middle and inner ear hearing structures, including the auditory nerve and its central projection, in developing chick embryos. Propylthiouracil (PTU), 2 mg, was injected into the albumin of fertile chick eggs on the 10th incubation day. Single doses of L-thyroxine (range 1-100mug) were inoculated in a similar manner, either alone or with PTU. Control inocula included sterile saline or water. After hatching, each chick was examined for obvious malformations. The thyroid glands, middle and inner ear mechanisms, auditory nerve, and brainstem were studied grossly and with different histologic staining techniques. When compared to controls, chicks exposed to PTU on their 10th incubation day exhibited: increased mortality, delayed hatching, reduced size, incomplete yolk sac absorption, and death within 5 days unless exogenous thyroid hormone was provided in the first 24-48 hr after hatching. Specific, consistent, morphologic alterations were observed in their thyroid glands as well as in the sensory hair cells of the acoustic papilla and cells of the spiral ganglion of the cochlea. Our data also indicate that if 50-75 mug of L-thyroxine is given simultaneously with (or as long as 120 hr after) the PTU injection on the 10th incubation day, one cannot detect the gross defects, marked thyroid lesions, or abnormal histology in cells of the cochlea and its ganglion. A relationship between embryonic thyroid gland function and the hearing mechanism of the chick embryo is suggested.
Intermediate-density lipoprotein as an independent risk factor for aortic atherosclerosis in hemodialysis patients.
Authors: T Shoji, Y Nishizawa, T Kawagishi, K Kawasaki, H Taniwaki, T Tabata, T Inoue, H Morii
Journal: Journal of the American Society of Nephrology (1998)

Patients with chronic renal failure often show accumulation of intermediate-density lipoprotein (IDL). Because recent studies have emphasized the atherogenicity of IDL in the general population, we evaluated the relationship between this lipoprotein and aortic atherosclerosis in uremic patients treated with hemodialysis. Aortic pulse wave velocity (PWV) was measured as a noninvasive index of sclerotic change of aorta in 205 hemodialysis patients and 184 age- and gender-matched healthy subjects. Fasting plasma lipoproteins were fractionated by ultracentrifugation into very low-density lipoprotein (VLDL), IDL, LDL, and HDL. Plasma lipoprotein (a) (Lp(a)) was measured by a latex immunoturbidimetric assay. Aortic PWV was significantly higher in the hemodialysis patients than in the control subjects. The hemodialysis group showed a significant increase in VLDL and IDL cholesterol, whereas their LDL and HDL cholesterol were lower than the control levels. Lp(a) levels did not differ between the two groups. In the hemodialysis population, VLDL, IDL, and LDL cholesterol correlated positively with aortic PWV adjusted for age, gender, smoking, and BP, whereas Lp(a) did not. Multiple regression analyses indicated that plasma triglycerides, independent of HDL cholesterol, had a significant association with aortic PWV in the hemodialysis patients but not in the control subjects. Further analyses revealed that aortic PWV in the hemodialysis patients had a significant and independent association with IDL cholesterol, whereas aortic PWV in the control subjects had significant and independent associations with HDL cholesterol and Lp(a). These results demonstrate that IDL is the lipoprotein fraction most closely associated with aortic PWV in the hemodialysis patients.
Prognostic Significance of CpG Island Methylator Phenotype and Microsatellite Instability in Gastric Carcinoma
Authors: Changhyeok An, In-Seon Choi, James C. Yao, Samidha Worah, Keping Xie, Paul F. Mansfield, Jaffer A. Ajani, Asif Rashid, Stanley R. Hamilton, Tsung-Teh Wu
Journal: Clinical Cancer Research (2005)

The influence of molecular characteristics in prognosis of gastric cancer remains unclear. The aim of this study was to evaluate the prognostic value of the CpG island methylator phenotype (CIMP) and microsatellite instability (MSI) in gastric cancer.We studied the methylation profiles of tumor suppressor gene p16, DNA mismatch repair gene hMLH1, and four CpG islands (MINT1, MINT2, MINT25, and MINT31) using bisulfite/methylation-specific PCR, and MSI using five microsatellite markers in 83 resected gastric carcinomas. The CIMP and MSI status were compared with clinicopathologic features and overall survival.Concordant methylation of multiple genes/loci (CIMP-high) was present in 31% of tumors and in 4% of non-neoplastic mucosa, CIMP-low in 55% and 17%, and CIMP-negative in 13% and 79%, respectively (P < 0.001). The prevalence of MSI-high, MSI-low, and MS-stable in tumor was 19%, 17%, and 64%, respectively. MSI status was closely associated with hMLH1 hypermethylation and CIMP status (P = 0.001). In univariate analysis, overall survival was predicted by pathologic stage (P < 0.0001), R0 resection (P = 0.0002), MINT31 methylation (P = 0.04), and CIMP-high status (P = 0.04). MSI status of tumor was not a significant predictor of prognosis. Although CIMP status seemed to be a prognostic predictor of gastric cancer, only pathologic stage remained a significant predictor of prognosis on multivariate analysis (P < 0.001).Our results indicate that there is an association between CIMP status and MSI status in gastric cancer. Concordant methylation of multiple genes/loci (CIMP-H) is associated with better survival but is not an independent predictor of prognosis in resected gastric cancer.
Spondyloarthritis: state of the art and future perspectives
Authors: Désirée van der Heijde, Walter P Maksymowych
Journal: Annals of the Rheumatic Diseases (2010)

Advances in the understanding of this group of arthritides over the past decade can be considered transformational from the perspective of basic mechanisms as well as clinical research focusing on the development of imaging technologies and a spectrum of standardised clinical outcomes that aim at a more comprehensive understanding of disease activity, functioning and disability, and prognosis. Prior to this decade, treatment was unsatisfactory and limited to physical modalities and non-steroidal anti-inflammatory agents, while diagnostic ascertainment primarily focused on clinical evaluation and plain radiography. Today, patients with spondyloarthritis (SpA) can look forward to earlier diagnosis and more effective treatment but significant challenges remain. This review will summarise the past decade's major accomplishments in the understanding of the basic mechanisms contributing to the development of SpA, outline those advances in clinical and imaging outcomes that have enabled major therapeutic advances and now permit a broader understanding of the early development of disease and its impact on patient well-being, and will describe new approaches to the development of diagnostic criteria that incorporate advances in imaging.
Toll-like Receptor-4 Is Up-Regulated in Hematopoietic Progenitor Cells and Contributes to Increased Apoptosis in Myelodysplastic Syndromes
Authors: Christos I. Maratheftis, Evangelos Andreakos, Haralampos M. Moutsopoulos, Michael Voulgarelis
Journal: Clinical Cancer Research (2007)

Abstract Purpose: To investigate the function and expression of Toll-like receptors (TLR) in bone marrow cells of myelodysplastic syndrome (MDS) patients and to examine their involvement in the apoptotic phenomenon characterizing MDS hematopoiesis. Experimental Design: TLR mRNA and protein expression was investigated in bone marrow cell populations of MDS patients and controls. TLR-4 ability to recognize lipopolysaccharide and up-regulate self mRNA and protein expression was examined. Tumor necrosis factor involvement in the constitutive and lipopolysaccharide (LPS)-induced TLR expression was also evaluated. Possible correlation between TLR-4 overexpression and apoptosis was investigated by simultaneous staining with Annexin V and TLR-4. Results: TLR-2 and TLR-4 are expressed in almost all bone marrow cell lineages including megakaryocytes, erythroid cells, myeloid precursors, monocytes, and B lymphocytes and are up-regulated in MDS patients compared with controls. In hematopoietic CD34+ cells, TLR-4 is also expressed and significantly up-regulated at both the mRNA and protein levels. Treatment with an anti–tumor necrosis factor antibody reduces both constitutive and LPS-induced TLR-4 levels. Increased TLR-4 expression correlates with increased apoptosis as TLR-4 is almost exclusively found in apoptotic bone marrow mononuclear and CD34+ cells. The addition of the TLR-4 ligand LPS further enhances the apoptosis of these cells. Conclusions: TLR-4 and other TLRs are significantly up-regulated in MDS patients whereas TLR-4 is involved in promoting apoptosis, possibly contributing to MDS cytopenia.
Reversal by Vasopressin of Intractable Hypotension in the Late Phase of Hemorrhagic Shock
Authors: David Morales, John Madigan, Suzanne Cullinane, Jonathan Chen, Mark Heath, Mehmet Oz, Juan A. Oliver, Donald W. Landry
Journal: Circulation (1999)

Background —Hypovolemic shock of marked severity and duration may progress to cardiovascular collapse unresponsive to volume replacement and drug intervention. On the basis of clinical observations, we investigated the action of vasopressin in an animal model of this condition. Methods and Results —In 7 dogs, prolonged hemorrhagic shock (mean arterial pressure [MAP] of ≈40 mm Hg) was induced by exsanguination into a reservoir. After ≈30 minutes, progressive reinfusion was needed to maintain MAP at ≈40 mm Hg, and by ≈1 hour, despite complete restoration of blood volume, the administration of norepinephrine ≈3 μg · kg −1 · min −1 was required to maintain this pressure. At this moment, administration of vasopressin 1 to 4 mU · kg −1 · min −1 increased MAP from 39±6 to 128±9 mm Hg ( P &lt;0.001), primarily because of peripheral vasoconstriction. In 3 dogs subjected to similar prolonged hemorrhagic shock, angiotensin II 180 ng · kg −1 · min −1 had only a marginal effect on MAP (45±12 to 49±15 mm Hg). Plasma vasopressin was markedly elevated during acute hemorrhage but fell from 319±66 to 29±9 pg/mL before administration of vasopressin ( P &lt;0.01). Conclusions —Vasopressin is a uniquely effective pressor in the irreversible phase of hemorrhagic shock unresponsive to volume replacement and catecholamine vasopressors. Vasopressin deficiency may contribute to the pathogenesis of this condition.
A simple method for estimating the intensity of purifying selection in protein-coding genes
Authors: R. Ophir, T. Itoh, D. Graur, T. Gojobori
Journal: Molecular Biology and Evolution (1999)

We propose a method by which the intensity of purifying selection on a functional protein-coding gene is estimated by using three aligned homologous sequences: a processed pseudogene (psi), a functional paralog from the same species (g), and a functional ortholog from a different species (o). For each such trio, we calculate the numbers of nucleotide substitutions along the branches leading to psi and g, i.e., K psi and K(g). If we assume that the mutation rates are the same in the genes and the pseudogenes and that mutations occurring in a pseudogene do not affect the fitness of the organism, we can show that the fraction of mutations that are selectively neutral, fg, is equal to the ratio K(g)/K psi. Since advantageous mutations occur only very rarely, such that they do not contribute significantly to the rate of molecular evolution, the fraction of deleterious mutations that are subject to purifying selection is 1-fg. Therefore, the K(g)/K psi ratio can be used directly to estimate the intensity of purifying selection, thereby isolating its effects on the rate of evolution from those of mutation. We compared the selection intensities of 12 orthologous protein-coding pairs from humans and murids. As expected, the fraction of mutations that are subject to purifying selection is strongest in the second codon position and weakest in the third. Interestingly, the mean fractions of effectively neutral mutations in the third codon position were only 41% and 42% for murids and humans, respectively, indicating that many synonymous mutations are subject to selective constraint. In several orthologous genes, we found that the intensity of purifying selection is very different between murid and human orthologous genes. There was no statistically significant difference in overall intensity of purifying selection between humans and murids. Thus, purifying selection does not seem to be an important factor contributing to the observed differences in the rates of evolution between these two taxa.
Long-term follow-up of acute and chronic non-A, non-B post-transfusion hepatitis: evidence of progression to liver cirrhosis.
Authors: G Realdi, A Alberti, M Rugge, A M Rigoli, F Tremolada, L Schivazappa, A Ruol
Journal: Gut (1982)

The long-term outcome of non-A, non-B post-transfusion hepatitis was evaluated in 21 patients who developed the illness after open-heart surgery and could be followed thereafter up to five years. Histological chronic sequelae were documented in 13 patients, and consisted of chronic persistent hepatitis in one case, chronic lobular hepatitis in two and chronic active hepatitis in 10, five of whom also developed superimposed cirrhosis. Progression to these chronic states was in most cases symptomless, independently of the severity of liver lesions; one patient, however, died of gastrointestinal bleeding due to cirrhosis of the liver. During follow-up the biochemical pattern of chronic non-A, non-B hepatitis was unique, while striking fluctuations of transaminase levels. Liver histology proved essential to identify the severity of chronic liver lesions, as clinical and biochemical features were uniform and not indicative of it. Our results suggest that cirrhosis may develop, often with an asymptomatic course, in a significant number of patients who do not recover after acute post-transfusion non-A, non-B hepatitis.
The surgical management of menorrhagia
Authors: J. A. Abbott
Journal: Human Reproduction Update (2002)

Surgical treatment of menorrhagia is likely to be both successful and satisfactory to the patient. Correct diagnosis of the cause of menorrhagia is essential, and management should be directed to the specific cause of the problem. The question of which treatment is best is a complex one and involves balancing patient wishes, expected outcomes, complications, cost-effectiveness and quality of life issues. For the subset of women in whom dysfunctional uterine bleeding is diagnosed, the literature suggests that there is a hierarchy of treatments that, in descending order for both efficacy and patient acceptability, are: (i) hysterectomy; (ii) endometrial ablation (either first- or second-generation); (iii) the levonorgestrel intrauterine system; and (iv) medical treatments. All four of these options should be discussed with the patient and the relative advantages and disadvantages considered before a treatment decision is made. For patients in whom a pathological cause is diagnosed, specific treatments should be aimed at removal of the lesion and observation of the effect on menstrual status. In addition to the treatment options above, specific treatments such as hysteroscopic, laparoscopic or open excision of the lesion need to be considered. For interventional radiological procedures such as uterine artery embolization, further study is recommended before it can be considered as a safe and effective treatment for menorrhagia.