bluuebunny/crossref_metadata_2025 huggingface dataset:
Geometric Morphometrics in Primatology: Craniofacial Variation in Homo sapiens and Pan troglodytes
Authors: Lynch John M. , Wood Chris G. , Luboga Sam A.
Published: April 2017

Traditionally, morphometric studies have relied on statistical analysis of distances, angles or ratios to investigate morphometric variation among taxa. Recently, geometric techniques have been developed for the direct analysis of landmark data. In this paper, we offer a summary (with examples) of three of these newer techniques, namely shape coordinate, thin-plate spline and relative warp analyses. Shape coordinate analysis detected significant craniofacial variation between 4 modern human populations, with African and Australian Aboriginal specimens being relatively prognathous compared with their Eurasian counterparts. In addition, the Australian specimens exhibited greater basicranial flexion than all other samples. The observed relationships between size and craniofacial shape were weak. The decomposition of shape variation into affine and non-affine components is illustrated via a thin-plate spline analysis of Homo and Pan cranial landmarks. We note differences between Homo and Pan in the degree of prognathism and basicranial flexion and the position and orientation of the foramen magnum. We compare these results with previous studies of these features in higher primates and discuss the utility of geometric morphometrics as a tool in primatology and physical anthropology. We conclude that many studies of morphological variation, both within and between taxa, would benefit from the graphical nature of these techniques.
Effects of Distension and Acetylcholine on Intestinal Blood Flow in vivo
Authors: Brobmann G.F. , Jacobson E.D. , Brecher G.A.
Published: April 2017

In vivo canine gut segments perfused by branches of the superior mesenteric artery were subjected to increased intraluminal pressure to observe the effects upon arterial inflow, measured with an electromagnetic blood flowmeter, and venous effluent collected by a cannula. Inflation of the intestinal segment with air simultaneously reduced both inflow and outflow. Intra-arterial infusion of acetylcholine increased blood flow, even with intraluminal pressure maintained at 40 mm Hg. Mechanical distension of the gut impedes blood flow, but this effect can be overridden by a vasodilator. These findings correspond to results observed in similar experiments on in vitro gut segments.
Besonderheiten der kontraktilen Eigenschaften der Koronargefäss-Muskelzellen und ihre Ursachen
Authors: Laszt L.
Published: April 2017

The contractile behaviour of the smooth muscle of coronary vessels was studied in the cow and in the horse after different kinds of stimulus. The findings obtained with bovine vessels as well as the differences between cow and horse vessels are attributed to the existence of vasoactive substances in the vessels of the cow and their lack in those of the horse.
Chronic Venous Insufficiency Treated with Hydroxyethylrutosides (HR)
Authors: Sørensen Halborg , Hansen H.
Published: April 2017

The effect of hydroxyethylrutosides (HR) on a series of 64 patients is reported. All patients received 400 mg 3 times daily. These patients were divided into groups as follows. Thirty cases of uncomplicated chronic venous insufficiency, in which a clear reduction of oedema, pain and restlessness of the legs was demonstrated; 6 patients with post-traumatic oedema in which 5 Showed quick resolution of the oedema; 15 patients with cramps due to arterial ischaemia, in which an improvement was obtained only in the milder cases; 10 cases of ‘idiopathic leg cramps’ in which a very marked improvement resulted; 3 isolated cases of Raynaud’s Disease which resulted in a quite dramatic improvement. Thus the most clear and assured effect of HR seems to be an anti-oedematous one, and may be explained by an action on resorption at a capillary or venule level. Such an effect is shown to be useful in chronic venous insufficiency.
Effect of External Lymph Drainage and of Coumarin Treatment on Dextran Edema
Authors: Földi-Börcsök Ethel , Földi M.
Published: April 2017

A significant protective effect is afforded against dextran oedema by external thoracic duct cannulation; the protective effect of coumarin is even more pronounced. The theoretical background of these phenomena is discussed.
Effects of Phenoxybenzamine and Norepinephrine on Transmitter Release in the Pulmonary Artery of the Rabbit
Authors: McCulloch M.W. , Bevan John A. , Su Che
Published: April 2017

The effects of phenoxybenzamine and norepinephrine (NE) on the release of tritiated NE were studied in spiral strips of the rabbit pulmonary artery. Phenoxybenzamine increased the tritiated NE efflux induced by transmural stimulation at 4 Hz by a factor of three. The magnitude of this effect was inversely related to the frequency of stimulation. NE (2.5 × 10–6 m) decreased the enhancing effect of short exposure but not long exposure to phenoxybenzamine, probably by surmounting the phenoxybenzamine blockade of the α-adrenergic receptors on the adrenergic nerve terminal. The transmitter output per pulse increased with the frequency from 4 to 16 Hz and decreased at 32 Hz. This evidence suggests that a negative feedback mechanism does operate in this vascular preparation but, probably because of the wide neuromuscular cleft, is less effective than in tissues with a narrower synaptic interval.
Depression by Local Cooling of 3H-Norepinephrine Release Evoked by Nerve Stimulation in Cutaneous Veins
Authors: Vanhoutte Paul M. , Verbeuren Tony J.
Published: April 2017

Experiments were performed to investigate whether local cooling facilitates adrenergic neurotransmission in the cutaneous vein of the dog. Helical strips of saphenous veins were incubated with 3H-noreρineρhrine and mounted for isometric tension recording and superfusion. The superfusate was collected for measurement of total radioactivity or for chromatographic analysis. Electrical stimulation (2 Hz) caused contraction and augmented the efflux of 3H-norepinephrine and metabolites. Cooling (from 37 to 28 °C) imposed during electrical stimulation caused a further increase in tension, but decreased the amount of 3H-norepinephrine and metabolites overflowing into the superfusate. These experiments demonstrate that the potentiating effect of cooling on the response of cutaneous veins to sympathetic nerve stimulation is not associated with facilitation of adrenergic neurotransmission. It probably is due to an altered sensitivity of the vascular smooth muscle to the transmitter.
Effects of Sex Hormones on the Passive Mechanical Properties of Rat Carotid Artery
Authors: Cox R.H. , Fischer G.M.
Published: April 2017

The effects of chronic administration of estradiol and testosterone on the passive mechanical properties of carotid arteries were determined using castrated and noncastrated male rats. Blood vessel segments were removed from the animals and mounted in a bath at in vivo length. Measurements of external diameter and transmural pressure were made in response to inflation in the presence of smooth muscle inhibitors. These data were used to determine stress-strain relations and values of incremental elastic moduli for the various arteries. Relative to arteries from control animals, passive tangential stress-strain curves for arteries from estradiol treated rats were found to be shifted significantly to the right, i.e., to larger strains. Similar data for testosterone-treated arteries were shifted to the left, but the effect was smaller than the former one and only significant for values of tangential stress greater than 2 × 10–6 dyn/cm2. At specific values of wall strain, estradiol produced a decrease in incremental elastic modulus relative to the arteries from control animals, while testosterone produced an increase in elastic modulus which was only significant for strains > 0.7. Quantitatively, similar results were found in castrated and noncastrated rats. These results are consistent with the concepts that estradiol decreases the stiffness of arteries while testosterone to a smaller degree increases the latter through the effects of these steroids on connective tissue accumulation in the arterial wall.
Presynaptic Muscarinic and α-Adrenergic Receptor Blocking Effect of Atropine on the Noradrenergic Neurones of the Rabbit Pulmonary Artery
Authors: Nedergaard Ove A. , Schrold Jørgen
Published: April 2017

The effect of atropine on the electrical-field stimulation-evoked overflow of tritium from isolated rabbit pulmonary arteries preincubated with 3H-noradrenaline was studied. Atropine (10–4M) and phentolamine (10–6M) increased stimulation-induced overflow of tritium. Clonidine (10–6 to 10-5 M) and acetylcholine (10–6 M) diminished the stimulation-evoked overflow of tritium. After the overflow had been raised by either atropine (10–4M) or phentolamine (10–6 M), clonidine (10–6 M) decreased the overflow below control values. Clonidine (10–5M) prevented the enhancement of tritium overflow evoked by atropine (10–4M). A lower concentration of clonidine (10–6 M) only caused a partial prevention. Enhancement of the overflow by phentolamine (10–6 and 3 × 10–5M) was not altered by atropine (10–4M). Atropine (10–7M), in a concentration which was without any effect on the stimulation-induced tritium overflow, prevented the reduction evoked by acetylcholine (10–6 M). It is concluded that atropine in a low concentration blocks presynaptic inhibitory muscarinic receptors; at higher concentrations it blocks in addition presynaptic α-adrenoceptors.
Differences in Proliferation of Primary Cultures of Vascular Smooth Muscle Cells Taken from Male and Female Rats
Authors: Travo P. , Barrett G. , Burnstock G.
Published: April 2017

Vascular smooth muscle cells from thoracic aortas of 10-week-old rats were cultured on different substrates. Cells taken from male animals proliferated more quickly than those taken from females; this was true for all substrates, but the difference was accentuated by growth on collagen membranes. The relationship between these results and the sex-linked incidence of hypertension and atherosclerosis is discussed and a model for future studies proposed.
Heterogeneity of Presynaptic Serotonin Receptors on Sympathetic Neurones in Blood Vessels
Authors: Göthert M. , Molderings G.J. , Fink K. , Schlicker E.
Published: April 2017

Presynaptic serotonin (5-HT) receptors on the postganglionic sympathetic nerves, which mediate inhibition of noradrenaline release in blood vessels of various species and which interact with the presynaptic α2-autoreceptors, are heterogeneous. In the rat vena cava, they are of the 5-HT1B subtype, in the pig coronary artery they belong to a novel, so far unknown class of 5-HT receptors, and in the human saphenous vein they could be classified as 5-HT1D. These results point to marked species differences and the need to carry out experiments in human vascular preparations. Presynaptic 5-HT receptors may be involved in the mechanism of action of the new antimigraine drug sumatriptan.
Nucleotides as Cotransmitters in Vascular Sympathetic Neuroeffector Transmission
Authors: Starke K. , von Kügelgen I. , Bulloch J.M. , Illes P.
Published: April 2017

Postganglionic sympathetic cotransmission by noradrenaline (NA) and adenosine 5’-triphosphate (ATP) was studied in isolated arteries from rabbits using as tools α-adrenoceptor antagonists and αβ-methylene-ATP which first activates and then desensitizes purine P2X receptors. In the pulmonary artery, NA was the only chemical signal responsible for neurogenic vasoconstriction. In sharp contrast, ATP was the only signal eliciting electric as well as mechanical postjunctional responses in small jejunal arteries. Mixed adrenergic and purinergic transmission was found in the largest ramus caecalis of the ileocolic artery. The purinergic component prevailed in short pulse trains and early in long trains, whereas the adrenergic component prevailed in the late phases of long (20 s) trains. Prejunctional α2-adrenergic autoinhibition markedly depressed purinergic as well as adrenergic transmission as soon as a latency of about 2 s was exceeded.
Innervation and Effects of Dilatory Neuropeptides on Cerebral Vessels
Authors: Edvinsson Lars
Published: April 2017

The cerebral circulation is supplied with two vasodilator systems: the parasympathetic system storing vasoactive intestinal peptide, peptide histidine isoleucine, acetylcholine and in a subpopulation of nerves neuropeptid Y, and the sensory system, mainly originating in the trigeminal ganglion, storing substance P, neurokinin A and calcitonin gene-related peptide (CGRP). Recent knowledge of the innervation and effects of the dilator neuropeptides in the cerebral circulation is reviewed. Their role in the pathophysiology of subarachnoid hemorrhage and migraine has now received attention, with documentation of a clear linkage with the release of CGRP. In subarachnoid hemorrhage, other perivascular peptides are, to a lesser extent, involved.
Postischemic Cerebral Blood Flow and Neuroeffector Mechanisms
Authors: Macfarlane Robert , Moskowitz Michael A. , Tasdemiroglu Erol , Wei Enoch P. , Kontos Hermes A.
Published: April 2017

The influence of neuroeffector mechanisms in the regulation of postischemic cerebral blood flow was investigated by microsphere determination in 8 cats after chronic unilateral vascular deafferentation by trigeminal ganglionectomy. The animals were subjected to 90 min of reperfusion following 10 min of global ischemia induced by 4-vessel occlusion and systemic hypotension. Cortical hyperemia 30 min after reperfusion was attenuated by up to 48% in cortical gray matter ipsilateral to the side of trigeminal ganglionectomy (p < 0.01). Axon reflex mechanisms involving the release of neuropeptides from peripheral sensory nerve fibers, such as substance P (SP), calcitonin gene-related peptide (CGRP) and neurokinin A (NKA), mediate this response. SP and NKA cause vasodilation by endothelium-dependent mechanisms (endothelium-dependent relaxing factor), whereas CGRP relaxes vascular smooth muscle by direct receptor interactions. Studies were therefore undertaken to determine the extent to which endothelium-dependent mechanisms mediate the hyperemia following global cerebral ischemia. In 7 intact cats, the postischemic response of pial arterioles to the topical application of acetylcholine (ACh; 10–7 M), an endothelial-dependent vasodilator, was measured using a closed cranial window technique. Although ACh increased pial arteriolar caliber by 17 % under resting conditions, the same dose elicited a vasoconstrictor response (87% of pre-ACh diameter 30 min after reperfusion) for the first 60 min of reperfusion after 10 min of ischemia. ACh-induced vasodilation was restored by 75 min (105%), but was less than control even at 120 min (109 vs. 117%; p < 0.05). The ability of sensory denervation to attenuate cortical hyperemia, combined with the demonstrated loss of endothelium-dependent vasodilation during the early postischemic period, indicates that CGRP, a nonendothelium-dependent vasodilator, is a likely mediator of postischemic hyperperfusion.
β-Adrenergic Receptor Stimulates L-Type Calcium Current in Adult Smooth Muscle Cells
Authors: Welling Andrea , Felbel Jochen , Peper Klaus , Hofmann Franz
Published: April 2017

The hormonal regulation of L-type calcium current was investigated in freshly isolated tracheal smooth muscle cells using the whole-cell configuration of the patch-clamp technique. Isoproterenol stimulated the L-type calcium current 2.6-fold through β-adrenoceptors. Dialysis of these cells with cyclic AMP, cyclic AMP analogues or the catalytic sub-unit of cyclic AMP kinase had no effect on basal or isoproterenol-stimulated calcium current. The calcium current was stimulated and inhibited by dialysis of the cells with GTPγS and GDPβS, respectively. Evidently, in some smooth muscle cells the β-adrenoceptor couples directly to L-type calcium channels via a G protein.
Is There a Role for the Vascular Renin-Angiotensin System in the Determination of Vascular Structure?
Authors: Mulvany M.J.
Published: April 2017

This paper reviews previous work done by my laboratory to investigate the effect of treatment with angiotensin-converting enzyme (ACE) inhibitors on blood pressure and small artery structure in spontaneously hypertensive rats (SHRs). First, the data confirm that ACE inhibitors have a persistent effect on blood pressure in SHRs when treatment is withdrawn. The effect of the ACE inhibitors was dose-dependent, but the persistent effect was not dose-dependent. This suggests that the persistent effect of ACE inhibitors on blood pressure in SHRs is not mediated through vascular structure. Secondly, the data demonstrate that, although ACE inhibitors have dose-dependent effects on both blood pressure and vascular structure, in experiments where different drugs were used, the effect of ACE inhibitors on vascular structure seems to be explained primarily through their effect on blood pressure, rather than any specific drugs effect.
Differential Skinning of Smooth Muscle: A New Approach to Excitation-Contraction Coupling
Authors: Pfitzer G. , Boels P.J.
Published: April 2017

In intact smooth muscle, the calcium sensitivity of force may increase as well as decrease. Using differently skinned smooth muscle preparations, two pathways involved in the change of calcium sensitivity of force have been identified: in microarteries skinned with β-escin, GTP (possibly via a G protein) is involved in sensitization to Ca2+, while in porcine coronary arteries skinned with Triton X-100 cyclic AMP and possibly cyclic GMP are involved in desensitization. In both cases, there is a corresponding change in the phosphorylation of the regulatory light chain of myosin, suggesting that the balance of phosphorylating to dephosphorylating reactions is altered at constant [Ca2+].
Modest Pressure Natriuresis and Autoregulation during Water Diuresis in Dogs
Authors: Waugh William H.
Published: April 2017

The effects of renal arterial pressure change on renal output of sodium and volume were measured during water diuresis in 25 chloralose-anesthetized dogs. Conditions included a minimal invasive stress, limited sodium administration, and mean renal arterial pressures varied suprarenally, by aortic balloon inflation to lowermost levels of 82–106 mm Hg. Group A dogs received no aldosterone; group B, C and D dogs were given aldosterone. Dogs of group C also received (1-Sar, 8-Ile)-angiotensin II. Group D dogs received phenylephrine which elevated arterial and right atrial pressures moderately without decrease in renal blood flow. In groups A, B and C, mean changes in sodium output, volume output, fractional excretions and free water clearances were not detectable with mean renal arterial pressure reductions, which averaged 29 ± 2.9, 22 ± 2.8 and 27 ± 5.2 mm Hg, respectively. Right atrial pressures, effective renal blood flows and glomerular filtration rates did not change with the renal arterial pressure changes in these groups. In the group D dogs, during the larger pressure reductions of 54 ± 6.6 mm Hg from higher values of 158 ± 7.0 mm Hg, mean urine flow and effective renal blood flow remained constant while glomerular filtration rate and sodium output decreased only slightly. Output efficiency ratios related to perfusion pressure were calculated. With no more than modest pressure-induced excretory changes, it is concluded that excretory sodium and urinary volume autoregulation in concert with nearly perfect circulatory autoregulation were demonstrated with regionally varied mean renal arterial pressure. The same preglomerular myogenic responses to transvascular pressure, which restrict glomerular and transcapillary pressures, are viewed dominantly responsible for both circulatory and excretory autoregulation under normal conditions of minimal stress and low fractional sodium excretions. Homeostatic implications are discussed concerning likely relevance to the Guyton-Coleman theory for the long-term control of arterial blood pressure.
Intracellular pH Measurement with Fluorescent Dye in Canine Basilar Arteries
Authors: Yu J. , Zheng J.J. , Ong B.Y. , Bose R.
Published: April 2017

The intracellular pH (pHi) of basilar artery rings was determined with 2’,7’-bis-(carboxyethyl)-5,(6)-carboxyfluorescein (BCECF) by measuring the ratio of emitted (540 nm) fluorescence intensities (FI) at excitation wavelengths of 500 and 440 nm. There was a dye loss from the rings in 90 min (39.3 ± 3.6%; p < 0.001). We found that the ratio of fluorescence intensities does not adequately correct for dye loss; hence, we derived a method to correct for dye loss during pHi determinations. Calibration curves of the ratio versus pH, were constructed for the artery rings. The slope and intercept of the calibration curves depended on FI440. Linear regression lines for the slope and intercept versus FI440 were: slope = 0.00343 × FI440 + 0.32484 (r – 0.96; p < 0.0001) and intercept = –0.02048 × FI440 – 0.80123 (r = –0.97; p < 0.0001). In solutions with different pH and different concentrations of free BCECF, the slope of the ratio versus pH of the solution was steeper at high concentrations of BCECF. Thus, pH was calculated from a calibration curve in which the slope and intercept were determined from FI440 with the above formula. The corrected pHi was 7.37 ± 0.05 (n = 25) at pHo 7.4 and 37 °C.
Multiple Serotonin Receptors on Large Arterioles in Striated Muscle
Authors: Alsip Nancy L. , Harris Patrick D. , Durrani Gary E.
Published: April 2017

In rat striated muscle, serotonin (5-hydroxytryptamine; 5-HT) constricts large arterioles (first-order; A1) via 5-HT2 receptor activation but dilates smaller arterioles via a 5-HT1-like receptor. In this preparation, A1 arterioles possess little basal tone. The purpose of this study was to determine if 5-HT would elicit A1 dilation if arteriolar tone was first induced. In anesthetized rats, A1 diameters of the cremaster muscle were measured via in vivo videomicroscopy. Topical application of angiotensin II caused a 26 ± 3 % constriction of the vessels. 5-HT dilated the preconstricted Als by 36 ± 7% while constricting normal tone Als by 33 ± 5%. This dilation was enhanced by blocking 5-HT2 receptors with LY53857, but abolished with methysergide, a 5-HT1 and 5-HT2 receptor antagonist indicating that the dilation was mediated by a 5-HT1-like receptor. Thus, A1 arterioles possess both 5-HT2 and 5-HT1-like receptors. The net result of 5-HT application in striated muscle, dilation or constriction, will depend on the initial tone of the vessels.
Effects of Buflomedil on Microvascular Disorders in Diabetic Patients
Authors: Dévéhat Le , Vimeux M. , Bondoux G. , Khodabandehlou T.
Published: April 2017

The aim of this work was to evaluate the effect of buflomedil on hemorheologic, hemodynamic and microcirculatory properties in diabetic patients. Patients were 20 non-insulin-dependent diabetics with distal arteriopathy characterized by chronic hypoxia (transcutaneous oxygen pressure = 25.2 ± 4.8 mm Hg). They were randomly assigned to two groups for a double-blind study versus placebo. The treatment consisted of a 4-hour intravenous perfusion of 400 mg of buflomedil or placebo as a daily dose during 7 days. Results showed significant improvements in hemodynamic parameters such as post-occlusive peak flow and time to peak flow at the end of buflomedil treatment. In the same manner, the transcutaneous oxygen pressure was found to be significantly increased after buflomedil treatment, whereas there was no modification by placebo. Indeed, red cell aggregation was significantly less important as a result of buflomedil treatment whilst red cell deformability was found to be significantly increased. These hemorheological improvements make the blood flow redistribution through the microcirculatory network easier and lead ultimately to better tissue oxygenation.
Clinical Feature and Bowel Ultrasound in Crohn’s Disease – Does Additional Information from Magnetic Resonance Imaging Affect Therapeutic Approach and When Does Extended Diagnostic Investigation Make Sense?
Authors: Girlich Christiane , Ott Claudia , Strauch Ulrike , Schacherer Doris , Obermeier Florian , Jung Ernst Michael , Schölmerich Jürgen , Schreyer Andreas Georg , Klebl Frank
Published: April 2017

Background/Aims: Some suggest MRI to be superior to ultrasound in Crohn’s disease. We analyzed how often MR enterography (MRE) following a routine ultrasound leads to a change in therapeutic decision. Material and Methods: We retrospectively evaluated 47 patients with Crohn’s disease undergoing routine ultrasound examination. Actual medical history, complete blood count, C-reactive protein (CRP), and sonographic findings were assessed independently by two specialists who retrospectively provided a therapeutic proposal. Additionally, all patients received MRE. Thereafter, the specialists had to provide a new therapeutic concept regarding all the available information. Results: Evaluation of the rectum was not successful by ultrasound, but MRE gave good results. Only 1 of 7 abscesses was identified sonographically. Three of the abscesses missed at sonography were localized in the perirectal/perianal region. MRE detected more inflamed bowel segments, but ultrasound assessment of anatomically fixed bowel parts showed good recognition by MRE. With increasing CRP values, we found more positive results of ultrasound and MRE. Therapeutic change was suggested in only 18 patients. Conclusions: Ultrasound should be performed by an experienced examiner, and a proctological examination should be added. MRE is justified in cases of discrepancy between clinical findings and the results of diagnostic ultrasound and, moreover, if Crohn’s lesions are suspected at sites proximal to the terminal or neoterminal ileum.
Association of Serum Adipocytokines with Hepatic Steatosis and Fibrosis in Patients with Chronic Hepatitis C
Authors: Baranova Ancha , Jarrar Mohammed H. , Stepanova Maria , Johnson Andrew , Rafiq Nila , Gramlich Terry , Chandhoke Vikas , Younossi Zobair M.
Published: April 2017

Background: The pathogenic mechanisms of hepatic steatosis in hepatitis C (HCV) remain unclear. Aim: To assess the potential role of cytokines and adipokines in HCV-related steatosis and fibrosis. Methods: We profiled several adipokines, cytokines, and related soluble molecules in 99 HCV patients and analyzed their potential associations with hepatic steatosis and fibrosis. Results: Serum leptin and IL-1RA were significantly higher in HCV genotype 1 as compared to genotype 3. On the other hand, serum resistin, IL-8, IL-1B and sIL-6R, were significantly higher in HCV genotype 3. No differences were observed for adiponectin, visfatin, IL-6 and TNF-α. Regardless of HCV genotype, steatosis could be predicted by a combination of IL-8, IL-6, and sIL-6R/IL-6. When analysis was repeated for each of the genotypes, the reliability of models improved. Regardless of HCV genotype, moderate to severe fibrosis (Metavir score >F2), was predicted by IL-8 and resistin levels. Conclusions: Analysis of adipocytokines associated with steatosis supports the hypothesis that steatogenic pathways differ in HCV genotype 3 from those infected with non-genotype 3 infections.
Expression Profile of p63 in 127 Patients with Laryngeal Squamous Cell Carcinoma
Authors: Borba M. , Cernea C. , Dias F. , Faria P. , Bacchi C. , Brandão L. , Costa A.
Published: April 2017

Objectives: To evaluate p63 expression in laryngeal squamous cell carcinoma and its prognostic significance. Methods: p63 expression was examined by immunohistochemistry and scored in 127 patients with laryngeal squamous cell carcinomas. Results: Sixty-two cases had scored 3, sixty had scored 2, four had scored 1 and one case did not show any expression (48.8, 47.2, 3.1 and 0.8%, respectively). Overall survival was 73.9% at 24 months and 59.5% at 60 months. The disease-free survival was 77.2 and 75.1%, and the disease-specific survival was 79 and 67% at 24 and 60 months, respectively. Uni- and multivariate analysis identified that decreased immunoexpression of protein p63 was a statistically significant factor for the risk of recurrence and death by cancer. Conclusions: p63 expression was highly prevalent in laryngeal squamous cell carcinomas, and its underexpression was correlated with a worse prognosis.
Acute Myeloid Leukemia with a RUNX1-RUNX1T1 t(1;21;8)(q21;q22;q22) Novel Variant: A Case Report and Review of the Literature
Authors: Kim Hanah , Moon Hee-Won , Hur Mina , Yun Yeo-Min , Lee Mark Hong
Published: April 2017

Variants of t(8;21)(q22;q22) account for approximately 3% of all t(8;21) in acute myeloid leukemia (AML). We report a 63-year-old female patient with AML, who showed a 3-way novel variant of t(8;21), t(1;21;8)(q21;q22;q22). She presented with gastric discomfort and splenomegaly, and her complete blood count was: white blood cell count 7.96 × 109/l, with 7% blasts; hemoglobin 8.3 g/dl, and platelets 66 × 109/l. Her bone marrow showed increased blasts (32.5%) with a basophilic cytoplasm, salmon-pink granules and Auer rods. Cytogenetic analysis revealed a karyotype of 46,XX,t(1;21;8)(q21;q22;q22), and fluorescence in situ hybridization confirmed a RUNX1-RUNX1T1 fusion signal on the derivative chromosome 8. After induction chemotherapy, the patient achieved complete remission and has been stable for 6 months. To the best of our knowledge, this is the first report on the novel variant of t(8;21) involving the breakpoint 1q21 and the third case with a translocation among chromosomes 1, 21 and 8. Although the clinical relevance of variant t(8;21) is still unclear, a review of 24 such cases in the literature does not imply a poorer prognosis of variant t(8;21) than of the classic t(8;21).
Photodynamic Therapy for Variant Central Serous Chorioretinopathy: Efficacy and Side Effects
Authors: Gupta B. , Mohamed M.D.
Published: April 2017

Background: Retinal pigment epithelial detachment (PED) is a recognised associated finding in central serous chorioretinopathy (CSC). We report our experience in treating patients using photodynamic therapy (PDT) in a variant of chronic CSC that presents with only an isolated PED. We present long-term follow-up data and novel observations on the pattern of retinal pigment epithelium (RPE) changes seen after treatment. Methods: Retrospective case series. Results and Discussion: CSC with subfoveal PED can be associated with a poor visual prognosis especially when the PED becomes chronic. PDT has been used to treat typical CSC with good outcomes. Three eyes in 3 patients were successfully treated with PDT, using the Treatment of Age-Related Macular Degeneration with Photodynamic Therapy protocol. However, marked RPE disturbance was observed after treatment directly overlying the areas of brisk choroidal hyperpermeability.
Mechanisms Balancing Tolerance and Immunity in the Liver
Authors: Böttcher Jan P. , Knolle Percy A. , Stabenow Dirk
Published: April 2017

The liver has a pivotal role in glucose, lipid and protein metabolism as well as in removal of toxins and waste products. A unique microanatomy and a network of resident scavenger cell populations specialized in endocytic uptake of antigens and macromolecules cooperatively mediate these salient hepatic functions together with parenchymal hepatocytes. Antigens taken up by hepatic scavenger cell populations, such as Kupffer cells, hepatic dendritic cells, stellate cells and liver sinusoidal endothelial cells (LSECs), can be (cross-)presented on MHC class I and II molecules, which leads to modulation of T cell immune functions. Among these cell populations, LSECs are endowed with the highest scavenger activity and are the most efficient cell population in cross-presenting soluble exogenous antigens to CD8 T cells. Together with their large number and the high cumulative surface area, LSECs represent the hepatic cell population that is best situated to interact with circulating T cells. Under physiological conditions, antigen-specific interaction of LSECs with CD8 T cells induces tolerance that is characterized by nonresponsiveness towards T cell receptor-mediated stimulation. In contrast to functional maturation of dendritic cells by activation through pattern recognition receptors, there is no such maturation in antigen-presenting LSECs, demonstrating that even under inflammatory conditions induction of CD8 T cell tolerance is preserved. However, upon viral infection of LSECs, a unique program of T cell differentiation into effector cytotoxic T cells is initiated that is independent of currently known costimulatory signals. These results highlight specific mechanisms operative in liver-resident antigen-presenting cells governing the local balance between tolerance and immunity.
Genetic Variants in the Promoter Region of the ALOX5AP Gene and Susceptibility of Ischemic Stroke
Authors: Ji Ruijun , Jia Jianping , Ma Xin , Wu Jian , Zhang Yanli , Xu Liqing
Published: April 2017

Background: Despite accumulating evidence supporting the association between variants of the ALOX5AP gene and atherosclerotic vascular events, the precise mechanism is still unclear. No variants in the coding sequence that lead to amino acid substitution have been found. We investigated genetic variants in the promoter region of the ALOX5AP gene and the association with ischemic stroke in a north Chinese Han population. Methods: 505 cases of ischemic stroke and 500 age- and gender-matched controls of the north Chinese Han population were enrolled. Genetic variants in the promoter region of the ALOX5AP gene were identified by polymerase chain reaction and DNA sequencing. 40 cases and 40 controls were randomly selected and compared for serum leukotriene B4 (LTB4) concentration. The effect on ischemic stroke was evaluated by logistic regression. Results: Three genetic variants were identified, including a mutation (–519 G > A), an insertion and deletion polymorphisms (–581_582 Ins A) and a single nuclear polymorphisms (–946 A > G). Association study showed that the II genotype of –581_582 Ins A was significantly associated with ischemic stroke of a large artery atherosclerosis (OR = 3.50, 95% CI = 1.93–6.36, p = 0.0002) and undetermined etiology (OR = 3.66, 95% CI = 1.92–6.94, p = 0.0006). No significant association was found between the –519 GA genotype (OR = 0.35, 95% CI = 0.02–5.88, p = 0.46), –946 AG genotype (OR = 1.35, 95% CI = 0.85–2.16, p = 0.21) and ischemic stroke. There was no significant difference in serum LTB4 concentration between cases (n = 40) and controls (n = 40) (log serum LTB4 of cases vs. controls: 2.67 ± 0.14 vs. 2.73 ± 0.18 pg/ml, p = 0.10). However, the serum LTB4 concentration was significantly higher in participants with the II genotype of –581_582 Ins A (n = 12) than that of participants with the DD genotype (n = 68) (log serum LTB4 of participants with II genotype vs. DD genotype: 2.82 ± 0.18 vs. 2.68 ± 0.15 pg/ml, p = 0.01). Conclusion: The –581_582 Ins A polymorphism might be a novel genetic risk factor for ischemic stroke in a north Chinese Han population. Further studies on molecular mechanism are warranted.
Apoptosis-Inducing Factor Is Involved in Gentamicin-Induced Vestibular Hair Cell Death
Authors: Zhang Daogong , Fan Zhaomin , Han Yuechen , Bai Xiaohui , Liu Wenwen , Lu Sumei , Wang Mingming , Xu Lei , Luo Jianfen , Li Jianfeng , Wang Haibo
Published: April 2017

Aim: Vestibular hair cell loss in response to different stimuli may be attributable to the occurrence of apoptosis, in which apoptosis-inducing factor (AIF) is an important regulator mediating apoptotic process independent of caspases. This study was designed to investigate the possible involvement of AIF in gentamicin (GM)-induced vestibular hair cell death. Methods: Vestibular organs from postnatal day 3 or 4 rats were maintained in tissue culture and were exposed to 2 mg/ml GM for up to 72 h. Vestibular hair cell viability was quantified by MTT assay. Apoptosis was determined by flow cytometry. AIF activation was examined by RT-PCR. The expressions of the mitochondrial protein and cytoplasm protein of AIF were detected by Western blot. Results: GM could significantly inhibit the cell viability of vestibular hair cells in a dose- and time-dependent manner. The number of apoptotic cells treated with GM was higher than that of cells not treated with GM. RT-PCR showed upregulation of AIF mRNA under GM. Western blot showed that AIF from mitochondria was decreased, whereas AIF from cytoplasm was increased after GM exposure. Conclusions: AIF participates in GM-induced apoptosis of vestibular hair cells.
MicroRNA-372 Is Associated with Poor Prognosis in Colorectal Cancer
Authors: Yamashita Shinya , Yamamoto Hirofumi , Mimori Koshi , Nishida Naohiro , Takahashi Hidekazu , Haraguchi Naotsugu , Tanaka Fumiaki , Shibata Kohei , Sekimoto Mitsugu , Ishii Hideshi , Doki Yuichiro , Mori Masaki
Published: April 2017

Objective: MicroRNA-372 (miR-372) is reportedly shown to be an oncogene in human testicular germ cell tumors and gastric cancers, but its expression in colorectal cancer (CRC) is not yet determined. This study investigated the clinical significance of miR-372 expression in CRC. Methods: qRT-PCR was used to evaluate miR-372 in 144 CRC patients, and large tumor suppressor 2 (LATS2) expression was also examined as the likely target gene of miR-372. In vitroassays were performed to evaluate the biological function of miR-372. Results: Multivariate analysis indicated that high miR-372 expression was an independent prognostic factor (p = 0.006). High miR-372 expression was associated with synchronous liver metastasis (p = 0.035). We found an inverse relationship between miR-372 and LATS2 by qRT-PCR (p = 0.007) and immunohistochemistry (p = 0.042) using CRC tissue samples. Furthermore, pre-miR-372 led to a decrease in the LATS2 protein and an increase in proliferative activity of LoVo cells. We also found a significant association between low LATS2 expression and liver metastasis (p = 0.042). Conclusions: This study suggested that miR-372 was a novel independent prognostic factor in CRC. Our data suggest that LATS2 may serve as one of the target genes of miR-372 in clinical CRC tissues.
Cholangiocarcinoma Complicating Secondary Sclerosing Cholangitis from Cryptosporidiosis in an Adult Patient with CD40 Ligand Deficiency: Case Report and Review of the Literature
Authors: Rahman Monira , Chapel Helen , Chapman Roger W. , Collier Jane D.
Published: April 2017

A 43-year-old man with a hyper-immunoglobulin M syndrome due to CD40 ligand deficiency presented with insidious onset of recurrent diarrhoea and deranged liver function tests. Standard stool microscopy was repeatedly negative for cryptosporidia but immunofluorescent testing and polymerase chain reaction demonstrated the presence of infection eventually. Despite both paromomycin and nitazoxanide, he developed sclerosing cholangitis secondary to cryptosporidial infection. Whilst being considered for dual bone marrow and liver transplantation, he was found to have cholangiocarcinoma on imaging after three biopsies of a suspicious lesion. This is a rare complication of this combined immune deficiency predominantly in children that has not been reported previously in a long-term survivor with this condition.
Sexual Dimorphism in the Brain of the Monogamous California Mouse (Peromyscus californicus)
Authors: Campi Katharine L. , Jameson Chelsea E. , Trainor Brian C.
Published: April 2017

Sex differences in behavior and morphology are usually assumed to be stronger in polygynous species compared to monogamous species. A few brain structures have been identified as sexually dimorphic in polygynous rodent species, but it is less clear whether these differences persist in monogamous species. California mice are among the 5% or less of mammals that are considered to be monogamous and as such provide an ideal model to examine sexual dimorphism in neuroanatomy. In the present study we compared the volume of hypothalamic- and limbic-associated regions in female and male California mice for sexual dimorphism. We also used tyrosine hydroxylase (TH) immunohistochemistry to compare the number of dopamine neurons in the ventral tegmental area (VTA) in female and male California mice. Additionally, tract tracing was used to accurately delineate the boundaries of the VTA. The total volume of the sexually dimorphic nucleus of the preoptic area (SDN-POA), the principal nucleus of the bed nucleus of the stria terminalis (BNST), and the posterodorsal medial amygdala (MEA) was larger in males compared to females. In the SDN-POA we found that the magnitude of sex differences in the California mouse were intermediate between the large differences observed in promiscuous meadow voles and rats and the absence of significant differences in monogamous prairie voles. However, the magnitude of sex differences in MEA and the BNST were comparable to polygynous species. No sex differences were observed in the volume of the whole brain, the VTA, the nucleus accumbens or the number of TH-ir neurons in the VTA. These data show that despite a monogamous social organization, sexual dimorphisms that have been reported in polygynous rodents extend to California mice. Our data suggest that sex differences in brain structures such as the SDN-POA persist across species with different social organizations and may be an evolutionarily conserved characteristic of mammalian brains.
Posttraumatic Glioma: Report of a Case
Authors: Spallone Aldo , Izzo Chiara , Orlandi Augusto
Published: April 2017

For a long time, head injury has been considered as a possible causative factor for later development of brain tumors. However, the actual role of previous head trauma in the pathogenesis of intracranial tumors is still a matter of debate, also due to the possible medico-legal implications. Some authors have suggested several criteria for establishing a possible causal relationship between the aforementioned factors. We report a case of a left posterior paraventricular high-grade glioma which developed 20 years after a posttraumatic hematoma occurring in the same area. This case is reported in detail and the relevant literature is reviewed.
Coxsackievirus A6 and Hand,Foot and Mouth Disease:Three Case Reports of FamilialChild-to-Immunocompetent Adult Transmission and a Literature Review
Authors: Kaminska Karolina , Martinetti Gladys , Lucchini Renzo , Kaya Gürkan , Mainetti Carlo
Published: April 2017

Hand, foot and mouth disease (HFMD) is a highly contagious viral infection characterized by typical maculopapular or vesicular eruptions on the hands and feet and in the oral cavity. It affects predominantly children and/or immunocompromised adults. It usually follows a benign and self-limiting course. However, HFMD cases with severe or lethal complications such as encephalitis, meningitis, pulmonary edema and myocarditis have also been reported, mostly in children, but also in adults. High infectivity of HFMD has contributed to several large outbreaks of this disease in recent decades in East and Southeast Asia, the United States and Finland. The most common pathogens were Coxsackievirus A16, Enterovirus 71 and, recently, also Coxsackieviruses A6 and A10. Differences in the course of HFMD have been observed, depending on the virus type. Recently, many cases of atypical HFMD have been described in the literature with unusual morphology and/or localization of skin lesions. Atypical HFMD manifestations including vesiculobullous exanthema, often on the trunk or extremities, and perioral zone involvement were often caused by Coxsackievirus A6 infections. We present 3 cases of familial transmission of HFMD caused by Coxsackievirus A6 with some atypical features, benign course and complete recovery among immunocompetent adults.
Validation of the Revised International Prognostic Scoring System for Patients with Myelodysplastic Syndromes
Authors: Savic Aleksandar , Marisavljevic Dragomir , Kvrgic Vanja , Stanisavljevic Natasa
Published: April 2017

The objective of this study is to externally validate the recently published Revised International Prognostic Scoring System (IPSS-R) for myelodysplastic syndrome (MDS) and compare it with the International Prognostic Scoring System (IPSS). We conducted a retrospective study of 173 adult MDS patients who had not received disease-altering treatment. Using the Cox hazard method, we found the IPSS-R to be a significant predictor of survival (p < 0.001, hazard ratio, HR = 1.82, 95% confidence interval, CI 1.57-2.12) and time to acute myeloid leukemia (AML; p < 0.001, HR = 2.05, 95% CI 1.55-2.70). The IPSS-R has greater prognostic power for survival and time to AML compared with the IPSS, given higher Somers' D values (0.41 vs. 0.39 and 0.55 vs. 0.53, respectively). Using the log-rank test, we found a significant difference when comparing IPSS-R groups (p < 0.02), with the exception of the high-risk versus very high-risk group comparison. The IPSS-R reclassified low-risk and intermediate-1 IPSS groups into four groups (log-rank, p < 0.001) and intermediate-2 and high-risk IPSS groups into three groups (log-rank, p < 0.04, excluding high-risk vs. very high-risk comparison). We conclude that the IPSS-R has significant prognostic utility for MDS patients.
Suppressor of Cytokine Signaling 3 Is a Negative Regulator for Neointimal Hyperplasia of Vein Graft Stenosis
Authors: Xiang Shui , Liu Jinping , Dong Nianguo , Shi Jiawei , Xiao Yaqiong , Wang Yu , Hu Xingjian , Gong Li , Wang Wenshuo
Published: April 2017

Coronary artery bypass graft (CABG) surgery is one of the most effective treatments for coronary artery disease. However, neointimal hyperplasia and ultimate luminal occlusion that is caused by vascular smooth muscle cell (VSMC) migration, proliferation and inflammatory response impede the long-term prognosis. The SOCS3 protein is involved in modulating various autoimmune and inflammatory diseases. However, the role of SOCS3 in vein graft disease is still unclear. We found that the mRNA and protein expression levels of IL-1β, IL-6, MCP-1, ICAM-1, TNF-α, STAT3, P-STAT3 and SOCS3 were significantly higher in the graft samples compared to normal veins. After transfecting the recombinant adenovirus carrying the rat SOCS3 gene into cultured rat VSMCs or grafting veins in rat, SOCS3 overexpression was found to significantly inhibit VSMC migration and proliferation in vitro and neointimal hyperplasia in vivo, respectively. Furthermore, SOCS3 overexpression inhibited VSMC migration and growth in vitro and alleviated VSMC inflammation in vitro by inhibiting STAT3 activation and phosphorylation. In conclusion, SOCS3 is a crucial physiological negative regulator for vein graft failure and provides a novel target for vein graft stenosis therapy after CABG.