bluuebunny/crossref_metadata_2025 huggingface dataset:
Colour Clusters for Computer Diagnosis of Melanocytic Lesions
Authors: Seidenari Stefania , Grana Costantino , Pellacani Giovanni
Published: April 2017

Background: To overcome subjectivity and variability in the interpretation of dermoscopic images, image analysis programs, enabling the numerical description of melanocytic lesion images, have been developed. Objectives: Our aim was to assess a method for the description of colours in melanocytic lesion images, based on the subdivision of image colours into red, green and blue clusters. Methods: Melanomas and naevi of the test set were described by means of 23 colour clusters previously selected by a training set comprising 369 melanocytic lesion images. The diagnostic performance obtained by this automated method was compared to sensitivity and specificity of diagnosis of 4 dermatologists. Results: Colour cluster values significantly differed between melanomas and naevi. Moreover, sensitivity and specificity values of computer diagnosis were similar to those achieved by the dermatologists. Conclusion: Our image analysis program based on the assessment of one single parameter has the diagnostic accuracy of dermatologists employing dermoscopy on a regular basis.
Blood Tests for Asbestos-Related Mesothelioma
Authors: Maeda Masahiro , Hino Okio
Published: April 2017

Mesothelioma is an aggressive tumor arising from the mesothelium, and is usually associated with previous exposure to asbestos. The incubation period of the tumor may be described as 30–40 years, and the prognosis is dismal. Recently, serum markers for the diagnosis of mesothelioma have been reported as candidates. In this paper, we mini-reviewed the potential utility of ELISA systems as serum diagnostic markers for asbestos-related mesothelioma.
Efficacy of Consolidation High-Dose Chemotherapy with Ifosfamide, Carboplatin and Etoposide (HD-ICE) Followed by Autologous Peripheral Blood Stem Cell Rescue in Chemosensitive Patients with Metastatic Soft Tissue Sarcomas
Authors: Schlemmer Marcus , Wendtner Clemens-Martin , Falk Martin , Abdel-Rahman Sultan , Licht Thomas , Baumert Jens , Straka Christian , Hentrich Marcus , Salat Christoph , Hiddemann Wolfgang , Issels Rolf-Dieter
Published: April 2017

Background: Prognosis of patients with metastatic soft tissue sarcomas (MSTS) is poor even after response to doxorubicin-based chemotherapy. We report phase II data of high-dose chemotherapy and peripheral blood stem cell (PBSC) rescue in patients with MSTS responding to AI-G chemotherapy. Patients and Methods: From 1997 to 2002, 55 patients with MSTS were prospectively treated with 4 cycles of AI-G (doxorubicin 75 mg/m2, ifosfamide 6 g/m2 with G-CSF support). Responders received 2 further cycles of AI-G with collection of PBSCs. High-dose chemotherapy consisted of ifosfamide 12 g/m2, carboplatin 1.2 g/m2 and etoposide 1.2 g/m2 (HD-ICE) followed by reinfusion of PBSCs. Results: Twenty-one of 55 patients (38%) were assessed as responders (3 complete response, 18 partial response). All but 2 patients refusing treatment received high-dose chemotherapy with PBSC rescue leading to grade IV hematologic toxicity without severe infections in all patients. No toxic death occurred. After a median follow-up time of 30 months, the median progression-free time was 12 months and survival time was 22 months for the entire group. By intent-to-treat analysis the probability of 5-year progression-free survival was significantly higher for patients allocated to HD-ICE compared to patients receiving second-line chemotherapy after failure of AI-G (14 vs. 3%; p = 0.003). The estimated 5-year overall survival between the 2 groups was different (27% vs. not reached) but did not reach significance (p = 0.08). Conclusion: HD-ICE is feasible and promising in patients with chemosensitive MSTS. A randomized phase III trial is warranted to further define the role of HD-ICE as consolidation treatment in these patients.
Plausible Linkage of Hypoxia-Inducible Factor (HIF) in Uterine Endometrial Cancers
Authors: Fujimoto Jiro , Sato Eriko , Alam Syed Mahfuzul , Jahan Israt , Toyoki Hiroshi , Hong Bao Li , Sakaguchi Hideki , Tamaya Teruhiko
Published: April 2017

Objective: Angiogenesis is essential for the development, growth and advancement of solid tumors. Angiogenesis is induced by hypoxia with the angiogenic transcription factor hypoxia-inducible factor (HIF). This prompted us to study the clinical implications of HIF relative to angiogenesis in uterine endometrial cancers. Methods: Sixty patients underwent curative resection for uterine endometrial cancers. In the tissue of 60 uterine endometrial cancers, HIF-1α, HIF-2α and HIF-1β mRNA levels, and the ratio of angiopoietin (Ang)-2 to Ang-1 (Ang-2/Ang-1) mRNA levels were determined by RT real-time PCR; histochemical scores and localization of HIF-1α were determined by immunohistochemistry. Levels of basic fibroblast growth factor (bFGF), vascular endothelial growth factor (VEGF), thymidine phosphorylase (TP) and interleukin-8 (IL-8) were determined by enzyme immunoassay. Results: In stage I uterine endometrial cancers, HIF-1α histochemical scores and mRNA levels significantly increased with myometrial invasion of uterine endometrial cancers. HIF-1α histochemical scores and mRNA levels correlated with the levels of Ang-2/Ang-1 and IL-8. Conclusion: The angiogenic mediator HIF-1α, linked to Angs and IL-8, might work on angiogenesis with myometrial invasion of cancer cells in uterine endometrial cancers.
Dealing with Missing Data in Family-Based Association Studies: A Multiple Imputation Approach
Authors: Croiseau Pascal , Génin Emmanuelle , Cordell Heather J.
Published: April 2017

To test for association between a disease and a set of linked markers, or to estimate relative risks of disease, several different methods have been developed. Many methods for family data require that individuals be genotyped at the full set of markers and that phase can be reconstructed. Individuals with missing data are excluded from the analysis. This can result in an important decrease in sample size and a loss of information. A possible solution to this problem is to use missing-data likelihood methods. We propose an alternative approach, namely the use of multiple imputation. Briefly, this method consists in estimating from the available data all possible phased genotypes and their respective posterior probabilities. These posterior probabilities are then used to generate replicate imputed data sets via a data augmentation algorithm. We performed simulations to test the efficiency of this approach for case/parent trio data and we found that the multiple imputation procedure generally gave unbiased parameter estimates with correct type 1 error and confidence interval coverage. Multiple imputation had some advantages over missing data likelihood methods with regards to ease of use and model flexibility. Multiple imputation methods represent promising tools in the search for disease susceptibility variants.
Current Status and Clinical Applications of Cardiac Multidetector Computed Tomography
Authors: Halon David A. , Rubinshtein Ronen , Gaspar Tamar , Peled Nathan , Lewis Basil S.
Published: April 2017

Contrast-enhanced multidetector-row computed tomography (MDCT) is now capable of providing high-quality noninvasive views of cardiac anatomy and ‘instant’ noninvasive coronary angiography. With current generation 64-slice scanners, MDCT can be performed in most patients with minimal patient discomfort and high diagnostic accuracy. MDCT may obviate the need for invasive diagnostic angiography in patients with borderline symptoms or equivocal noninvasive testing. It is useful in assessing the symptomatic patient postrevascularization and in emergency room triage in selected patients with chest pain. Calcified vessels are still difficult to assess, as is the accurate evaluation of implanted coronary stents. The volume of contrast material required for proper opacification limits the use of MDCT in patients with renal dysfunction, but newer emerging technologies will greatly improve these disadvantages in the near future. MDCT is expected to become an integral part of our diagnostic armamentarium in the cardiac patient.
Blood-Derived Serum Albumin Contributes to Neurodegeneration via Astroglial Stress Fiber Formation
Authors: Moser Karma V. , Humpel Christian
Published: April 2017

Enhanced influx of blood-derived serum albumin into the brain is seen after blood-brain barrier disrupture and may induce neurodegeneration. The aim of the present study was to explore the effects of high levels of bovine serum albumin (BSA) on the survival of cholinergic neurons in organotypic brain slices of the basal nucleus of Meynert and in comparison in isolated primary astroglia. When brain slices were exposed to high BSA concentrations, a strong tissue shrinkage was observed accompanied with cholinergic cell death. The shrinkage was prevented by endothelial cell growth factor and heparin. In primary astrocytes, high BSA concentrations induced stress fiber formation, which was reduced by hydrocortisone or the phosphoinositol-3-kinase inhibitor LY294002. In conclusion, high BSA levels are neurotoxic for brain neurons. Cholinergic neurons are protected in an intact astroglial network, which might be of importance in neurodegenerative diseases, such as Alzheimer’s disease.
A Community Genetics Perspective on Consanguineous Marriage
Authors: Bittles A.H.
Published: April 2017

Consanguineous marriage has long been a controversial topic, with particular attention focused on adverse health outcomes. Unfortunately, the studies that have been conducted on consanguinity to date have usually lacked control for important sociodemographic variables, such as maternal age and birth intervals, and in estimating specific disease gene frequency, they have ignored the influence of population sub-division. Inadequate attention has also been paid to the social benefits associated with intra-familial marriage, resulting in a biased overall cost-benefit assessment. Worldwide, some 1,000 million people live in countries where 20 to more than 50% of marriages are consanguineous, and large migrant communities from these regions are now resident in Western Europe, North America and Oceania. The need for comprehensive and more balanced investigations into all aspects of consanguineous marriage is pressing and merits a substantial international collaborative research effort.
Does Offering Prenatal Screening Influence Pregnant Women’s Attitudes regarding Prenatal Testing?
Authors: Kleinveld Johanna H. , van den Berg Matthijs , van Eijk Jacques T.M. , van Vugt John M.G. , van der Wal Gerrit , Timmermans Daniëlle R.M.
Published: April 2017

Objectives: This study aims to find out whether offering prenatal screening for Down syndrome and neural tube defects influences pregnant women’s attitudes toward having a screening test. Methods: Women were randomised into a group that was offered prenatal screening and a group that was not offered screening (controls). Both groups completed questionnaires before screening was offered, after the offer (not the control group), and in the last trimester of pregnancy. Results: Women with a neutral attitude at baseline who accepted the screening test had a more positive attitude, decliners became more negative and the attitude of the control group did not change. Conclusion: Offering prenatal screening triggers a change in some pregnant women’s attitude regarding prenatal testing. This instability of women’s attitudes may pose a problem for determining whether some women made an informed choice.
Vasoactive Intestinal Peptide as a Healing Mediator in Crohn’s Disease
Authors: Arranz A. , Abad C. , Juarranz Y. , Leceta J. , Martinez C. , Gomariz R.P.
Published: April 2017

The vasoactive intestinal peptide/pituitary adenylate cyclase-activating peptide (VIP/PACAP) system is considered as a paradigm for the use of a neuroendocrine-immune mediator in therapy. We review the role of VIP in 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced colitis as a murine model of Crohn’s disease. VIP treatment led to the recovery of clinical factors, the amelioration of parameters related to the recruitment and traffic of cell populations, and the balance of inflammatory mediators derived from granulocytes, antigen-presenting cells and T lymphocytes including Th1, Th2 and Th17. Finally, the most recent data validate its therapeutic role through the modulation of TLR2 and 4 receptors.
Bilateral Endophthalmitis in a Patient with Bacterial Meningitis Caused by Streptococcus pneumoniae
Authors: Torii Hidemasa , Miyata Hiroshi , Sugisaka Eiko , Ichikawa Yuho , Shinoda Kei , Inoue Makoto
Published: April 2017

Aim: To present a patient who developed bilateral endogenous endophthalmitis secondary to Streptococcus pneumoniae meningitis. Methods: A 44-year-old man who was unconscious because of bacterial meningitis was referred to us for conjunctival hyperemia and decreased pupillary light reflexes. Ophthalmoscopy revealed inflammation in the anterior chamber and vitreous opacities in both eyes. He was diagnosed as having endogenous endophthalmitis associated with the meningitis. Ceftazidime and vancomycin hydrochloride were injected intravitreally and subconjunctivally repeatedly in both eyes. Results: Vision improved to 20/200 in the left eye 1 month later, but the right eye became hypotonic and blind. Vision deteriorated to light perception in the left eye due to a retinal detachment with proliferative vitreoretinopathy, and vitreous surgery successfully reattached the retina. Vision recovered to 20/80, and the retina has remained attached for 1 year. Conclusions: We recommend that endogenous endophthalmitis be suspected in cases of meningitis, and if present, intravitreal and subconjunctival antibiotics should be promptly given to preserve vision.
Vestibular Evoked Myogenic Potentials Are Heavily Dependent on Type I Hair Cell Activity of the Saccular Macula in Guinea Pigs
Authors: Lue June-Horng , Day An-Shiou , Cheng Po-Wen , Young Yi-Ho
Published: April 2017

This study applied the vestibular evoked myogenic potential (VEMP) test to guinea pigs coupled with electronic microscopic examination to determine whether VEMPs are dependent on type I or II hair cell activity of the saccular macula. An amount of 0.05 ml of gentamicin (40 mg/ml) was injected directly overlaying, but not through, the round window membrane of the left ear in guinea pigs.One week after surgery, auditory brainstem response test revealed normal responses in 12 animals (80%), and elevated thresholds in 3 animals (20%). The VEMP test using click stimulation showed absent responses in all 15 animals (100%). Another 6 gentamicin-treated animals underwent the VEMP test using galvanic stimulation and all 6 also displayed absent responses. Ultrathin sections of the saccular macula in the gentamicin-treated ears displayed morphologic alterations in type I or II hair cells, including shrinkage and/or vacuolization in the cytoplasm, increased electron density of the cytoplasm and nuclear chromatin, and cellular lucency. However, extrusion degeneration was rare and only present in type II hair cells. Quantitative analysis demonstrated that the histological density of intact type I hair cells was 1.1 ± 1.2/4000 μm2 in the gentamicin-treated ears, showing significantly less than that in control ears (4.5 ± 1.8/4000 μm2). However, no significant difference was observed in the densities of intact type II hair cells and supporting cells between treated and control ears. Furthermore, the calyx terminals surrounding the damaged type I hair cells were swollen and disrupted, while the button afferents contacting the damaged type II hair cells were not obviously deformed. Based on the above results, we therefore conclude that VEMPs are heavily dependent on type I hair cell activity of the saccular macula in guinea pigs.
Influence of Clonidine (Catapressan®-ST155) on the Muscle Blood Flow in the Legs of Hypertensive Patients (Antagonism of Tolazoline)
Authors: Amery A. , Bossaert H. , Clement D. , Deruyttere M. , Verstraete M.
Published: April 2017

Using the Xenon133 local clearance technique, the influence of clonidine on the blood flow in the tibial anterior muscle of hypertensive patients was studied. Within 10 min after a single, slow intravenous injection of 0.15 mg clonidine, the mean blood pressure and the resting muscle blood flow decreased significantly, while the calculated resistance in this vascular bed tended to increase. During chronic oral administration of varying doses of clonidine, no significant changes were found in the muscle blood flow and vascular resistance at rest; however, determined after maximal ischemic exercise, the muscle blood flow was significantly decreased and the vascular resistance increased. Twenty mg tolazoline, injected intravenously in patients under chronic clonidine treatment, increase pulse rate and blood pressure but further decrease the resting muscle blood flow in the first 15 minutes after the injection.
Klinisch manifeste Atherosklerose und Ergebnisse der biomikroskopischen und histologischen Konjunktivaluntersuchung
Authors: Mörl H. , Fuhrmeister H. , Ziegan J.
Published: April 2017

Seventy men, showing a clinical manifest atherosclerosis at an extensive angiological examination, were subjected to a biomicroscopical examination and a histological conjunctival examination as well for estimating the involvement of the terminal vessels. While the results of vitalmicroscopy stand only as a groups comparison in persons with healthy vessels, the histological conjunctival-examination shows to be an additional measure for estimating the grade of seriousness of the atherosclerosis in organism on account of the good coincidence of the alterations at the conjunctival vessels with the extent of atherosclerosis in the larger vessels.
Immunological Response to the Revascularisation of Experimental Myocardial Infarction
Authors: Ježková Z. , Bartoš J. , Pokorný J.
Published: April 2017

In experimental work on dogs, was performed a myocardial ischemia of differing duration. By means of a non-suture mammary-coronary artery anastomosis, a revascularisation was achieved. We realise that the diagnosis of the anastomostic potency using normal methods is not sufficiently clear. For this reason we tried to improve our diagnostic potential by means of antibody detection.
The Regulation of the Limb Circulation in Lymph-Oedema (Development of an Arteriovenous Shunt Circulation in Experimental Lymph-Oedema of the Leg)
Authors: Solti F. , Ungváry Gy. , Bálint A. , Nagy Z.
Published: April 2017

The effect of lymph stasis on limb blood flow was studied in 38 dogs where lymph-oedema of one of the hindlimbs was induced by ligation of the lymphatics on the thigh and of the regional lymph-node. Haemodynamic examinations were conducted in 17 animals; total blood flow and the nutritive flow to the muscles and skin (86Rb extraction) were determined in both hindlimbs. Microcirculation was studied in 16 dogs by means of the india ink-gelatin injection method, the benzidine reaction and by the polyvinylchloride injection technique. In all cases specimens were taken from muscle, skin and subcutaneous connective tissue of both hindlimbs for light microscopic analysis. The results presented indicate an increase in total blood flow without any change in the nutritive flow to the skin or muscle in the lymph-oedematous limb. Lymph stasis induced intimal swelling and plasma infiltration of the intima and media of small vessels (pre-capillaries and metarterioles) of skin, muscles and subcutaneous tissue, which led to a blocked transportation of proteins. Small vessels of the limb with lymph-oedema were spottily dilated, whereas at other areas compressed capillaries could be seen. Evidence is supplied for the appearance of arteriovenous shunt circulation in lymph-oedema of the lower limb. In a previous study we observed that, unlike venous congestion, lymph-oedema of the limbs in man was accompanied by increased blood flow and a conspicuously low arteriovenous oxygen difference in the limb. (1) This finding led us to assume that chronic lymph stasis may induce arteriovenous shunt circulation. The present experiments were designed to study relative changes of total and nutritive limb blood flow and to examine alterations of the microcirculation in experimental lymph-oedema of the limb.
The Treatment of Experimental Lymphedema
Authors: Földi-Börcsök Ethel , Casley-Smith J.R. , Földi M.
Published: April 2017

It has been shown previously, by plethysmographic measurements, that experimental lymphedema can be treated successfully by administration of coumarin and by massage. The present study confirms this fact by histological examination.
Angioorganopathie – ischämische Neuropathie
Authors: Glatzel W. , Preuss E.-G. , Tietze K.
Published: April 2017

Ill patients with angiopathies concerning the legs were neurologically and electromyographically explored; more over 14 of them suffered from diabetes mellitus. 88.8 % showed hypesthesia, 68.4 % disturbance of pallesthetic sensibility and 59.3% ataxia. The reflex excitability was more or less reduced for the patellar reflex in 61.3% and for the achilles reflex in 94.2% – scarcely only seldom abolished. Especially in states II, III and IV after Fontaine, action potentials of lower amplitude and subnormal duration were found electromyographically. Besides, more than usual action potentials with split points and polyphasic potentials were manifested. A retardation of the motor conduction velocity was at 36.5%. In perfect equality with the weight of the angiopathy, there was a corresponding stronger falling-off of single to many motor unities during maximal voluntary contraction as well as frequent disturbing of motor conduction velocity. Spontaneous discharges above all as fibrillation potentials were occasionally met. The neurologic and electromyographic disturbances were far more striking, in particular the retardation of the motor conduction velocity besides contemporary diabetes.
Catechol-O-Methyltransferase and Dopamine-β-HydroxyIase Activity in the Blood Vessels of Hypertensive Rats
Authors: Trajkov Trajko , Berkowitz Barry A. , Spector Sydney
Published: April 2017

Catechol-O-methyltransferase (COMT) activity was measured in the aorta and mesenteric arteries of hypertensive rats. In both spontaneously hypertensive rats (SHR) and uninephrectomized-DOCA salt treated hypertensive rats COMT activity per milligram vascular protein increased. The elevated COMT specific activity may be compensatory to the increased blood pressure and serve to increase catecholamine degradation. In contrast to the degradative enzyme, the activity per milligram vascular protein of a synthetic enzyme, dopamine-β-hydroxylase (DBH) decreased by 50% in the mesenteric artery of the SHR. We suggest the possibility that in some types of hypertension both the enzymes of synthesis and degradation may be altered simultaneously to regulate neurotransmitter activity.
Release of ATP from Perfused Heart during Coronary Vasodilatation
Authors: Paddle B.M. , Burnstock G.
Published: April 2017

The release of ATP into the coronary circulation during the vasodilatory response to hypoxia of the perfused guinea pig heart has been measured by the highly sensitive firefly luciferin-luciferase assay method. A reduction in perfusion pressure by more than 50% was accompanied by an increase in ATP concentration in the perfusate from 0.21 ± 0.05 to 0.64 ± 0.09 pmol/ml. When ATP (0.1 µM) was infused into the coronary circulation, about 99% was bound and/or metabolized during transit, indicating that the measured increase in perfusate ATP during hypoxia is likely to be a substantial underestimate of the true release. This conclusion is supported by experiments with the ATPase inhibitor ouabain, which markedly increased the amount of ATP in the perfusate from the hypoxic heart. Neither guanethidine nor hyoscine significantly altered the vasodilatory response to hypoxia, thus indicating that adrenergic and cholinergic nerves are not responsible. Guanethidine and hyoscine also had no effect on the release of ATP. The possibility that ATP is involved in the physiological regulation of coronary flow is discussed, as well as thequestion of whether the source of the ATP is anoxic cardiac muscle or purinergic nerves.
Fine Structural and Autoradiographic Study of the Adrenergic Innervation of the Dog Lateral Saphenous Vein
Authors: Coimbra A. , Ribeiro-Silva A. , Osswald W.
Published: April 2017

The tunica media of the dog lateral saphenous vein contains 8–12 layers of predominantly circular smooth muscle fibers. Numerous nerve profiles exhibit bright green fluorescence after formaldehyde gas treatment. These profiles occur amongst the muscle cells throughout the whole thickness of the media. Electron microscopy shows such profiles to be surrounded by Schwann cell processes enveloping axons which contain large (43%) and small (57%) dense-core vesicles. Axons are separated from muscle cells by 100–300 nm; in some cases intimate contacts, ≈20 nm wide, were seen between an axon and a muscle cell projection. After incubation of the vein with exogenous radioactive noradrenaline, nerves showed a great accumulation of radioactive material. Extraneuronal tissues (muscle and connective tissue) exhibit a much lower grain density (≈15 times less), which is, however, far above background levels. The dense innervation of the vessel wall and the intimate neuromuscular relationship are considered to form the morphological basis for the speed of nerve-evoked contractile responses in this preparation, as well as for the great extent of transmitter inactivation through neuronal reuptake.
Innervation Pattern and Neurogenic Response of Rabbit Veins
Authors: Bevan John A. , Hosmer David W. , Ljung Bengt , Pegram Barbara L. , Su Che
Published: April 2017

The adrenergic neuroeffector mechanism has been assessed in 14 different veins of the rabbit chosen to represent vessels of different, function and regional location. The pattern, distribution and density of the adrenergic innervation were assessed by fluorescence histochemistry. The magnitude of the neurogenic contractile response of isolated segments was studied in vitro in relation to the maximum response to 1-norepinephrine. The diameter and wall thickness of the veins was determined. The amount of adrenergic innervation determined histochemically was related to the size of the contractile response. Both fluorescence and response were absent in the superficial cervical, femoral, subcutaneous from back, brachial and deep circumflex iliac branch veins. The amount of adrenergic innervation increased in order in the renal, inferior vena cava, pulmonary, jugular, parietal branch of internal iliac, mesenteric, central ear, cephalic and small saphenous veins. In the latter two veins, innervation was not restricted to the adventitio-medial junction but entered the media. The pattern of innervation and contractile response may be related to the functional need for active venoconstriction in the various parts of the capacitance section of the vascular system.
Human Greater and Canine Lateral Saphenous Veins
Authors: Goldberg Michael R. , Joiner Paul D. , Hyman Albert L. , Kadowitz Philip J.
Published: April 2017

Canine lateral saphenous vein and human greater saphenous vein were studied together to determine similarities and differences. Helical strips of both vessels contracted to norepinephrine with similar sensitivity. Canine veins developed more isometric tension than human veins treated similarly. Histological studies show canine veins to have little connective tissue and a single circular layer of smooth muscle. Human veins have much connective tissue and three layers of smooth muscle, an inner circular layer, middle longitudinal layer and outer circular layer.
Comparison of the Relaxing Effect of Dopamine with that of Adenosine, Isoproterenol and Acetylcholine in Isolated Canine Coronary Arteries
Authors: Toda Noboru , Hojo Masakazu , Sakae Koichiro , Usui Hachiro
Published: April 2017

Isolated canine coronary arteries were contracted with prostaglandin F2α and the relaxing effects of dopamine, adenosine, isoproterenol and acetylcholine were compared. Relaxation induced by dopamine in phenoxybenzamine-treated arteries was not significantly influenced by propranolol and atropine in concentrations sufficient to shift dose-response curves of isoproterenol and acetylcholine, respectively, to the right. Dose-response curves of isoproterenol were shifted significantly to the left by 2 x 10–5 M aminophylline. In contrast, the relaxing effect of adenosine was significantly attenuated by aminophylline (5 × 10–6–10–4 M) in a dose-dependent manner. Kinetic analysis showed that aminophylline competitively antagonized the effect of adenosine, and the pA2 was 5.57. At these concentrations, aminophylline did not alter the relaxing action of dopamine and acetylcholine. It may be concluded that dopamine produces relaxation at a different site and with a different mechanism of action from those of isoproterenol, the effect of the latter being presumably mediated by cellular cyclic AMP, and that dopamine also does not share the site of action with adenosine and acetylcholine. It appears that receptive sites specific for adenosine are present in canine coronary arteries.
Isoenzymes of Lactate Dehydrogenase in Varicose Veins
Authors: Mrhová O. , Přerovský I.
Published: April 2017

The activity of lactate dehydrogenase and fractions of this enzyme has been estimated in human large saphenous veins. Typical varicosities were compared in composition with normal veins from the same patients. The total LDH activity was significantly decreased in typical varicosities. Varicose veins further differed from macroscopically normal veins by a lower content of aerobic fractions of LDH and a higher content of anaerobic fractions. These results suggest that there is a disturbance in metabolism of the smooth muscle of the venous wall in varicosities which would make the diseased wall more dependent on anaerobic glycolysis than normal tissue.
Rat Aortic Histamine Synthesis during Short-Term Hypertension
Authors: Yarnal James R. , Hollis Theodore M.
Published: April 2017

Thoracic aortic histamine synthesis has been examined in rats rendered hypertensive for periods ranging from ¼ to 8 days through ligation of the abdominal aorta between origins of the renal arteries, in a preliminary attempt to establish whether activity of the aortic nonmast-cell histidine decarboxylase system is increased in experimental hypertension. Results indicate that aortic histamine synthesis is increased 66, 75, 96 and 55% at postsurgical intervals of ¼, ½, 1 and 8 days. These data suggest at least one biochemical explanation for both increased arterial wall permeability and the arterial inflammation consistently associated with both clinical and experimental hypertension by resolving these into those associated with the prolonged inflammatory response.
Isolation and Characterization of Plasma Membrane from Rat Mesenteric Arteries
Authors: Wei Jiann-Wu , Janis Ronald A. , Daniel Edwin E.
Published: April 2017

A method for isolating a plasma membrane-enriched fraction and other subcellular fractions from rat mesenteric arteries by the use of a discontinuous sucrose density gradient is described. Electron microscopy showed both plasma membrane and endoplasmic reticulum fractions to be composed of vesicles. 5’-Nucleotidase, alkaline phosphatase, ouabain-sensitive (Na++K+)-ATPase and K+-phosphatase, and phosphodiesterase I were concentrated in the plasma membrane fraction. The increase in ATP-dependent calcium uptake in the presence of oxalate was greater in the endoplasmic reticulum than in the plasma membrane fraction. The lack of inhibition of active calcium uptake by azide suggests that the plasma membrane-enriched fraction was relatively free of mitochondrial contamination. Calcium uptake by the plasma membrane or the endoplasmic reticulum fraction was not enhanced by high-energy compounds other than ATP, and was little affected by 100 mM KCl or NaCl in the Mg++-containing medium. Subcellular fractions isolated by this method will be useful for investigating the biochemistry of small blood vessels of the rat.
A Comparative Study of the Role Played by Some Inactivation Pathways in the Disposition of the Transmitter in the Rabbit Aorta and the Saphenous Vein of the Dog
Authors: Brandão Fernando
Published: April 2017

The aim of this study was to determine the relative importance of neuronal uptake, catechol-O-methyltransferase (COMT) and diffusion in the disposition of endogenous noradrenaline (NA) in the rabbit aorta and dog saphenous vein. Helical strips of dog saphenous vein and rabbit aorta were stimulated transmurally, relaxation occurring either in oil or in Krebs-Henseleit solution. The rate of inactivation of NA by various mechanisms was assessed from the decrease in the rate of relaxation after blockade of one or more of these processes. Cocaine was used to inhibit neuronal uptake and COMT was blocked with 3,4-dihydroxy-2-methyl propiophenone. Diffusion out of the tissue was prevented by replacing the Krebs-Henseleit solution in the muscle bath with mineral oil. Neuronal uptake was the primary mechanism of inactivation in the saphenous vein whereas diffusion and COMT appear to be more important in the aorta. The differences in the relative importance of the inactivation mechanisms (neuronal uptake, O-methyltransferase and diffusion) existing between these two vessels are attributed primarily to differing density and distribution of the adrenergic innervation.
Specific α-Adrenergic Receptor Desensitization in Vascular Smooth Muscle
Authors: Carrier, Jr. Oliver , Wedell Eberhard K. , Barron Kirk W.
Published: April 2017

Specific desensitization of vascular tissue to norepinephrine was studied using an open-ring-type strip preparation of rabbit aorta. Aortae were taken from untreated, reserpine-pretreated (0.1 mg/kg/day; 3, 5, or 7 days) and 6-hydroxydopamine-pretreated (50 mg/kg; 3 or 7 days before sacrifice) rabbits. Aortic strips from the pretreated rabbits were supersensitive to norepinephrine. Subsequent to obtaining the first dose-response curve for norepinephrine, aortic strips were less sensitive to norepinephrine. It was found that desensitization to norepinephrine occurred following 10 min preincubation with 10–6 m norepinephrine, and 20 min preincubation with 10–7 m norepinephrine. The desensitization of supersensitive strips was significantly greater than in controls. Dopamine and isoproterenol desensitized both untreated and pretreated strips to norepinephrine. Phenylephrine desensitized strips to norepinephrine from 6-hydroxydopamine-pretreated rabbits. Acetylcholine and potassium did not desensitize strips to norepinephrine; however, acetylcholine desensitized strips to acetylcholine. It is concluded from these studies that norepinephrine desensitization is a specific α-adrenergic-related event.
Alterations in Lysosomes, Catalase-Containing Organelles, Mitochondria and Plasma Membrane Fragments from Hypertensive Rat Aorta and Caudal Artery
Authors: Stauber W.T. , Hedge A.M. , Schottelius B.A.
Published: April 2017

Vascular smooth muscle (VSM) cells from hypertensive and normotensive rat aortae and caudal arteries were isolated by enzymatic techniques, homogenized, and fractionated by differential pelleting. By these techniques, only mitochondria could be enriched more than fivefold in any one fraction. The other organelles were distributed heterogeneously in almost all fractions. Hypertensive smooth muscle enzyme distribution patterns were different from the normotensive, suggesting that changes in sedimentation characteristics had occurred. Activity of the enzyme 5’-nucleotidase increased in whole tissue homogenates and in the ‘microsomal’ fraction of aortic and caudal artery of hypertensive VSM. The lysosomal protease, cathepsin D, of hypertensive animals decreased in activity for both vascular smooth muscles while N-acetyl-β-glucosaminidase and pNPPase (acid phosphatase) increased. The possibility of a functional deficiency in protein degradation causing lysosomal overloading is discussed.
Quantitative Investigation of Sudanophilic Lesions around the Aortic Ostia of Human Fetuses, Newborn and Children
Authors: Sinzinger H. , Silberbauer K. , Auerswald W.
Published: April 2017

The sudanophilic lesions around the aortic ostia of 10 fetuses, 10 newborns and 10 children aged up to 1 year were studied using a polar coordinate mapping method. The periorificial sudanophilic lesions develop initially distal to the orifices and show a continuous increase with age in percentage and extent. In children the lesions nearly completely surround all the ostia with a significant distal peak. There was no sex difference; the involvement of the right and left side was comparable. The comparison of the morphological data from the parents and children with anamnestics showed no relationship.
Ontogenesis of Hypertension and Responsiveness to Antihypertensive Agents in Spontaneously Hypertensive Rats
Authors: Antonaccio Michael J. , Cavaliere Thomas , Cote Donald
Published: April 2017

Heart rate, systolic blood pressure and responses of spontaneously hypertensive rats (SHR) to guanethidine, timolol, minoxidil and phentolamine were monitored at 2, 6 and 12 months of age. All antihypertensive agents produced significant and comparable reductions in systolic blood pressure at 6 and 9 months of age, at which time systolic blood pressures were maximally elevated, but had very little effect at 2 months when pressures were only marginally higher. However, at 12 months of age, SHR maintained their response to guanethidine and timolol but responded less well to minoxidil and, especially, to phentolamine. Aortic strips of SHR contracted less than those of normotensive rats to both KC1 and norepinephrine at all ages and also relaxed less to nitroglycerin. SHR aortic strips appeared to specifically lose the ability to contract to norepinephrine at 12 months of age. It is suggested that a progression of change in responsiveness to antihypertensive agents exists for SHR. Furthermore, this progression will differ for agents with differing mechanisms of action and is probably a result of physical and/or biochemical factors which combine to alter the responsivity of SHR vascular smooth muscle.
Effect of Benzothiadiazine Derivatives on Cyclic Nucleotide Phosphodiesterase and on the Tension of the Aortic Strip
Authors: Vulliemoz Yvonne , Verosky Mariagnes , Triner Lubos
Published: April 2017

Diazoxide and chlorothiazide (0.1–1.5 mM) had a dose-dependent inhibitory effect on the rate of cAMP and cGMP hydrolysis determined in a 500-g supernatant of rat aorta homogenates; both compounds were weaker inhibitors of cAMP and cGMP hydrolysis than theophylline. cAMP and cGMP content of the aorta did not change in the presence of diazoxide or chlorothiazide; diazoxide, however, further increased the isoproterenol-induced rise in cAMP, while chlorothiazide did not. Both benzothiadiazines decreased the maximum tension of the aortic strip induced by serotonin, phenylephrine or potassium. Diazoxide was a stronger and chlorothiazide a weaker inhibitor of the contractile response than theophylline. Comparison of the biochemical and functional effects of diazoxide and chlorothiazide indicates that the inhibitory effect of these compounds on cyclic nucleotide phosphodiesterase does not by itself explain their vasodilating effect.
Functional and Morphological Properties of Human Omental Resistance Vessels
Authors: Aalkjær Christian , Mulvany Michael J.
Published: April 2017

We have examined the functional and morphological properties of arterial resistance vessels with lumen diameters about 200 µm from the human omentum. The vascular smooth muscle cells were circumferentially oriented and arranged in about 3 layers within the media. The cells, when held at a length where their contractile response was maximal, were 97 µm long and had a mean diameter of 3.9 µm. In response to maximum potassium stimulation the force developed per cell was 2.4 µN. The maximum response to norepinephrine (NE) was about 90% of the response to potassium, while the sensitivity to NE (NE-ED50 = 0.4 µM) was about the same as the NE sensitivity reported for larger human vessels. The sensitivity to NE was unaffected by cocaine, while the response to potassium was unaffected by phentolamine. Fluorescence microscopy indicated that the vessels contained few adrenergic nerve terminals. These findings suggest that although the vessels are well supplied with alpha-receptors, the vessels are only of minor importance for sympathetic blood pressure control.
Flow-Pressure Relationships in Newborn and Infant Spontaneously Hypertensive Rats
Authors: Karr-Dullien Vivian , Bloomquist Eunice I. , Beringer Theodore , El-Bermani Al-Walid I.
Published: April 2017

In flow-pressure studies of the perfused ‘forebody’, newborn (3–12 h old) SHR demonstrated significantly lower pressures than newborn WKY at high flow rates. Newborns from dams fed high salt during pregnancy showed no significant differences in flow-pressure relationships from newborns of the corresponding strain whose dams received standard salt. At 2 weeks, SHR continued on standard salt had pressures not significantly different from those of WKY at intermediate and high flow rates. However, 2-week standard salt SHR did demonstrate significantly lower pressures at low perfusion rates than 2-week WKY. 2-week SHR on high salt showed strikingly lower pressures at high flows than 2-week standard salt SHR.
A Comparative Study of the Relaxing Effect of Nitroprusside and Verapamil on Human Umbilical Vessels
Authors: Ozaki H. , Shibata S. , Kitano H. , Matsumoto P. , Ishida Y.
Published: April 2017

Relaxing effects of nitroprusside and verapamil on the resting or K-stimulated tension and 45Ca uptake in human umbilical vessels were investigated. Both nitroprusside and verapamil reduced the resting and K-stimulated tensions in a dose-dependent manner. Nitroprusside was much more effective than verapamil in reducing resting tension. However, verapamil caused a greater relaxation of the K-induced contraction than nitroprusside. In a Ca2+-free medium, K+ still caused a small and sustained contraction. Nitroprusside abolished the contraction in the Ca2+-free medium, which verapamil failed to inhibit. Neither nitroprusside nor verapamil affected the resting 45Ca uptake measured by a lanthanum method. The K-induced increase in 45Ca uptake was inhibited by verapamil, but not by nitroprusside. The results suggest that nitroprusside unlike verapamil does not act as a Ca2+ influx inhibitor resulting in the relaxation of human umbilical vessels.
Local Modulation of Neurotransmitter Release in Bovine Splenic Vein
Authors: Dzielak David J. , Thureson-Klein Åsa , Klein Richard L.
Published: April 2017

Bovine splenic vein has an abundant sympathetic innervation. Isolated strips were used to examine whether autoinhibition of norepinephrine release from the noradrenergic nerve terminals could be demonstrated under various experimental conditions and whether additional local regulatory modulators of transmitter release could also be implicated. In particular, the possibility of a histamine interaction with presynaptic inhibitory receptors was examined because ultrastructural evidence disclosed a close spatial relationship between mast cells and noradrenergic nerve terminals in the vessel wall. To investigate the presence of presynaptic α-receptors the competitive blocking agent phentolamine was included in the superfusion medium at concentrations ranging from 1 to 50 µM during electrical field stimulation at frequencies between 1 and 10 Hz. Transmitter outflow was measured as fractional tritium release. Low frequency stimulation (1 Hz) with 1 µM phentolamine resulted in the typical increase in norepinephrine release characteristic for presynaptic α-receptor inhibition. In contrast, high frequency (10 Hz) stimulation in the presence of 50 µM phentolamine caused an unexpected decrease in norepinephrine outflow. This unusual result can be explained by additional pharmacological actions of phentolamine unrelated to α-receptor blockade, e.g. histamine release from the mast cells which subsequently can act on presynaptic inhibitory histamine receptors. This effect, manifested at higher phentolamine concentrations, would overcome the α-receptor blockade. The presence of histamine receptors was supported by the results from electrical stimulation in the presence of exogenous histamine. Histamine decreased norepinephrine outflow while increasing basal tension and the contractile response of the vein strip. Unexpectedly, these effects appeared to be mediated by histamine receptors of the H1-type because they were reduced after pyrilamine but unaffected by agonists and antagonists to receptors of the H2-type. It is speculated that interactions between mast cells and noradrenergic nerve terminals may serve to maintain homeostasis in the bovine splenic vein.
Innervation Sites of Dog Hindpaw Series and Parallel Vascular Circuits
Authors: Baker Carleton H. , Davis Darrell L. , Lindsey Bruce G.
Published: April 2017

The neural control of the distribution of blood flow between the parallel nutritional and nonnutritional vascular circuits in the dog hindpaw has been assessed. The right hindpaw of anesthetized dogs was vascularly and neurally isolated and placed in a volume recorder sealed by the skin flap. The animals were heparinized. The autoperfused preparation was isovolumetric during the control period. The inflow tubing had side arms for measurement of perfusion pressure and for injections of indicators (131I-albumin, 86Rb and 85Sr-microspheres). Vascular volume changes were determined from venous time-concentration curves and by plethysmography. The peripheral cut ends of the superficial and deep fibular nerves and the tibial nerve were individually stimulated at 5 and 11 Hz. The permeability surface area product of 86Rb and the capillary filtration coefficient were determined and A-V shunt patency was assessed by the venous recovery of 85Sr 15 µm microspheres. Each nerve stimulation increased blood flow resistance. Superficial fibular nerve innervation included essentially uniform effects on the arterioles and A-V shunts, the upstream arteries and also the veins. Deep fibular nerve stimulation indicated that its innervation included the arteries and the A-V shunt nonexchange vessels. Tibial nerve stimulations indicated that its innervation included the A-V shunt vessels and veins with minimal influences on the arteries and arterioles.
Activation of Muscarinic and Serotonergic Receptors Results in Phosphoinositide Hydrolysis but Not in Mobilization of Calcium in Sympathetic Neurons
Authors: Wakade Taruna D. , Bhave Anjali S. , Bhave Sanjiv V. , Wakade Arun R.
Published: April 2017

The effects of various neurotransmitters on phosphoinositide hydrolysis, mobilization of Ca2+ and release of [3H]-norepinephrine ([3H]-NE) were studied in cultures of sympathetic neurons of chick embryos. [3H]-inositol-1,4,5-triphosphate ([3H]-IP3) was increased in sympathetic neurons by acetylcholine (ACh), muscarine and serotonin (5-HT). Dopamine and norepinephrine did not stimulate phosphoinositide hydrolysis. Intracellular concentration of free Ca2+ ([Ca2+]i) was measured in Indo-1-loaded sympathetic neurons at rest and after addition of test agents. Measurements were made in the cell body and growth cone regions since Ca2+ mobilization is known to be different in different regions of the sympathetic neurons. ACh (nicotinic component was blocked by hexamethonium) and 5-HT failed to increase the [Ca2+]i, in the cell body as well as in the growth cone. The spontaneous release of [3H]-NE was not affected by ACh and 5-HT. Caffeine increased the [Ca2+]i only in the cell body but not in the growth cone and had no effect on the release of [3H]-NE. These results suggest that an IP3-insensitive but caffeine-sensitive pool of Ca2+ is present only in the somatic region of sympathetic neurons and is not coupled to the transmitter release.