tbuckley/cabot-search huggingface dataset:
John (“Ian”) Gowan Gray
Authors: John Buchanan
Journal: BMJ (2006)

Former consultant surgeon North Staffordshire Royal Infirmary, Stoke on Trent (b 1927; q Edinburgh 1950; FRCS Ed, FRCS), died from pancreatic cancer on 11 December 2005.

John (“Ian”) did his national service in the Far East during the Korean war. His surgical training was at Glasgow Royal Infirmary and then Queen Elizabeth Hospital, Birmingham, as surgical lecturer. He spent a year as research fellow at the Massachusetts General Hospital, Boston, and Harvard Medical School, concentrating on transplant surgery and using this experience in his 1966 Hunterian professorship lecture at the Royal College of Surgeons. In 1965 he was appointed consultant surgeon in North Staffordshire, retiring in 1992. Predeceased by his wife, Margaret, he leaves six children and 11 grandchildren.
Radiological assessment of arterial branching coefficients
Authors: J. S. M. BEALES, R. E. STEINER
Journal: Cardiovascular Research (1972)

Measurements made on a series of normal aortograms show that at the bifurcation of the normal human aorta there is a mean decrease in the size of the vascular bed by a factor of 0·77. This decrease is also seen in patients with hypertension. Measurements made at a number of other arterial divisions show only a small increase in the size of the vascular bed (1·15-1·25). These findings conflict with previous necropsy reports and have important implications in the study of arterial blood flow.
Vascular Reactivity in Obstructive Sleep Apnea Syndrome
Authors: HANS W. DUCHNA, CHRISTIAN GUILLEMINAULT, RICCARDO A. STOOHS, JOHN L. FAUL, HEITOR MORENO, BRIAN B. HOFFMAN, TERENCE F. BLASCHKE
Journal: American Journal of Respiratory and Critical Care Medicine (2000)

The obstructive sleep apnea syndrome (OSAS) is associated with cardiovascular disease and systemic hypertension. Because systemic arterial blood pressure is proportional to venodilation and venous return to the heart, we hypothesized that altered vascular responsiveness might exist in the veins of subjects with OSAS. We therefore investigated venodilator responses in awake, normotensive subjects with and without OSAS, using the dorsal hand vein compliance technique. Dose-response curves to bradykinin and nitroglycerin were obtained from 12 subjects with OSAS and 12 matched control subjects. Maximal dilation (E(max)) to bradykinin was significantly lower in the OSAS group (62.1% +/- 26.1%) than in the control group (94.3% +/- 10.7%) (p < 0.005). Vasodilation to nitroglycerin tended to be lower in the OSAS group (78.6% +/- 31.8%) than the control group (100.3% +/- 12.9%), but this effect did not reach statistical significance. When six of the OSAS subjects were retested after 60 d of treatment with nasal continuous positive airway pressure (CPAP), E(max) to bradykinin rose from 60.3% +/- 20. 3% to 121.4% +/- 26.9% (p < 0.01). Vasodilation to nitroglycerin also increased, but this effect did not reach statistical significance. These results demonstrate that a blunted venodilatory responsiveness to bradykinin exists in OSAS. This effect appears to be reversible with nasal CPAP therapy.
Crack Cocaine and Cocaine Hydrochloride
Authors: Dorothy K. Hatsukami, Marian W. Fischman
Journal: JAMA (1996)

To review and discuss the differences and similarities between the use of crack cocaine and cocaine hydrochloride; and to determine how these findings might affect policies on the imprisonment and treatment of cocaine users.English-language publications were identified through a computerized search (using MEDLINE) between 1976 and 1996 using the search terms "smoked cocaine," "crack cocaine," "freebase," and "cocaine-base." In addition, manual searches were conducted on references cited in original research articles, reviews, and an annotated bibliography, and on selected journals.Only those articles that compared various routes of cocaine administration or types of cocaine (cocaine base or crack cocaine vs cocaine hydrochloride) were examined.Studies were reviewed to obtain information on the composition of the 2 forms of cocaine, and the prevalence, pharmacokinetics and pharmacodynamics, abuse liability, pattern of use, and consequences across the various routes of cocaine administration and forms of cocaine.Cocaine hydrochloride is readily converted to base prior to use. The physiological and psychoactive effects of cocaine are similar regardless of whether it is in the form of cocaine hydrochloride or crack cocaine (cocaine base). However, evidence exists showing a greater abuse liability, greater propensity for dependence, and more severe consequences when cocaine is smoked (cocaine-base) or injected intravenously (cocaine hydrochloride) compared with intranasal use (cocaine hydrochloride). The crucial variables appear to be the immediacy, duration, and magnitude of cocaine's effect, as well as the frequency and amount of cocaine used rather than the form of the cocaine. Furthermore, cocaine hydrochloride used intranasally may be a gateway drug or behavior to using crack cocaine. Based on these findings, the federal sentencing guidelines allowing possession of 100 times more cocaine hydrochloride than crack cocaine to trigger mandatory minimum penalties is deemed excessive. Although crack cocaine has been linked with crime to a greater extent than cocaine hydrochloride, many of these crimes are associated with the addiction to cocaine. Therefore, those addicted individuals who are incarcerated for the sale or possession of cocaine are better served by treatment than prison.
Cytomegalovirus Infection Persists in the Liver Graft in the Vanishing Bile Duct Syndrome
Authors: Joachim C. Arnold, Bernard C. Portmann, John G. O'grady, Nikolai V. Naoumov, Graeme J.M. Alexander, Roger Williams
Journal: Hepatology (1992)

Cytomegalovirus infection is one factor implicated in the cause of the vanishing bile duct syndrome complicating liver transplantation. To further investigate the role of cytomegalovirus in this syndrome, we studied serial liver biopsy material by in situ hybridization for cytomegalovirus DNA using a highly sensitive technique that allows the localization of viral replication. Cytomegalovirus DNA was identified in hepatocytes in 10 of 12 patients with the vanishing bile duct syndrome, 1 of whom had no serological evidence of cytomegalovirus infection. It was also present in all 18 patients with uncomplicated cytomegalovirus infection but was not identified in any of 10 subjects with transplants who had neither complication. Nine of the patients in this series underwent a diagnostic liver biopsy at 1 wk and subsequently had cytomegalovirus infection develop; cytomegalovirus DNA was identified in liver tissue of all nine patients, indicating that cytomegalovirus replication commences at an early stage. In those with uncomplicated cytomegalovirus, infection occurred earlier (p less than 0.05) but was eliminated more quickly (p less than 0.0005), and the number of infected hepatocytes was greater (p less than 0.05) when compared with those with the vanishing bile duct syndrome; in these, cytomegalovirus DNA was detectable until death or retransplantation. Cytomegalovirus DNA was never identified in either biliary or endothelial tissue. These data indicate that the vanishing bile duct syndrome is associated with persistent cytomegalovirus replication within hepatocytes.
Mucoepidermoid Carcinoma of the Thyroid with Concomitant Papillary Carcinoma: Comparison of Findings on Fine-Needle Aspiration Biopsy and Histology
Authors: Vikas Nath, Graham E. Parks, Mithra Baliga, Edgar O. Hartle, Kim R. Geisinger, Veena Shenoy
Journal: Endocrine Pathology (2014)
Immunisation against infectious disease.
Authors: K. M. Citron, J. A. Lunn
Journal: BMJ (1988)

ciation of the potential risks of not being im- munised many doctors do not use the opportunity to offer immunisation during routine consulta- tions; other strategies are needed to bring about change.These results suggest the importance of using more than one intervention to produce an improvement in performance.Although the system described was carried out using manual recording, the potential for this type of intervention using computers is greatly in- creased.Using these figures for interpractice comparisons, with due regard to their limitations, could be a useful way of improving motivation.
Eating Disorders in Austrian Men: An Intracultural and Crosscultural Comparison Study
Authors: Barbara Mangweth, Harrison G. Pope, Jr., James I. Hudson, Roberto Olivardia, Johannes Kinzl, Wilfried Biebl
Journal: Psychotherapy and Psychosomatics (1997)

Background: We compared 30 male university students with eating disorders and 30 male comparison subjects without eating disorders recruited by advertisement at Innsbruck University, Austria. Methods: Subjects were interviewed using instruments that we had previously used in a controlled study of college men with eating disorders in the United States. Results: The Austrian men with eating disorders differed sharply from Austrian comparison subjects, but closely resembled their American counterparts, on prevalence of personal and familial psychopathology, adverse family experiences, and scores on rating scales for eating disorder. Interstingly, dissatisfaction with body image was consistently greater among American subjects regardless of eating disorder status. Conclusions: Our data suggest a weak association between eating disorders and homosexual or bisexual orientation in men, and no consistent association between eating disorders and childhood sexual abuse.
4. Role of Notch1 in Augmenting Intracellular Trafficking and Transgene Expression of Recombinant Adeno-Associated Virus-2
Authors: Changchun Ren, April F. White, Selvarangan Ponnazhagan
Journal: Molecular Therapy (2006)

Adeno-associated virus-2 (AAV) has attracted considerable interest as a gene therapy vector over the past decade. Studies in the past few years have identified several cellular factors, which play key roles in receptor-mediated internalization, nuclear trafficking, and complementary strand synthesis of AAV2. We report here the significance of Notch1 receptor in intracellular trafficking and transgene expression of recombinant AAV2 by RNA microarray, confocal microscopy using fluorescent-conjugated virus, reporter gene expression and blocking assays to determine the roles of proteasome and endosome pathways. RNA profiling of human prostate cancer cell lines PCa2b, DU145, LNCaP with varying degrees of AAV transduction as compared to AAV2 permissive HeLa and non-permissive M07e cells indicated a correlation of the amount of Notch1 transcript to rAAV2 transgene expression. A definitive role of Notch1 in enhancing AAV2 transduction was confirmed by developing clonal derivatives of DU145 cells overexpressing either the full-length or the intracellular domain of Notch. To further discern the stage(s) of AAV2 transduction influenced by Notch1, competitive binding with soluble heparin, endocytic and intracellular trafficking using Cy3-labeled rAAV2, and blocking of proteasome and dynamin pathways were performed. Results indicate that in the absence or low level expression of Notch1, only binding of the vector was found on the cell membrane but internalization was impaired. However, reversal of Notch expression in these cells allowed efficient perinuclear accumulation of the labeled capsids and vector transduction. Although the presence of labeled capsids could not be detected in the nuclear compartment, nuclear transport of vector genome was evident from transgene expression. The addition of proteasome inhibitor doxorubicin did not exert any influence in transgene expression indicating the Notch-influenced enhancement is likely to be independent of proteasome pathway. Interestingly, the effect of Notch1 was not found to influence the transduction of AAV serotypes 1, 3, 4, 5 and 6. These studies provide additional insights into the underlying mechanisms of intracellular trafficking of AAV2 in different cell types, which may have implications in the optimal use of AAV2 in human gene therapy.
Defence subscriptions for general practitioners.
Authors: P. Fenn, R. Dingwall, C. Ham
Journal: BMJ (1988)

relieving the symptoms of the postmenopausal syndrome.Meanwhile, perhaps it would be wise to maintain circulating concentrations of oestradiol above 150 pmol/l, since this has been shown to relieve the postmenopausal syndrome and arrest bone loss,2 but below 440 pmol/l.Such an approach may enable the maximum clinical benefit to be obtained from replacement treatment with the minimum of risk.
A Macrophage NBR1-MEKK3 Complex Triggers JNK-Mediated Adipose Tissue Inflammation in Obesity
Authors: Eloy D. Hernandez, Sang Jun Lee, Ji Young Kim, Angeles Duran, Juan F. Linares, Tomoko Yajima, Timo D. Müller, Matthias H. Tschöp, Steven R. Smith, Maria T. Diaz-Meco, Jorge Moscat
Journal: Cell Metabolism (2014)
The Zero of Potential of the Electrical Field Produced by the Heart Beat
Authors: ROBERT H. BAYLEY, CONRAD L. KINARD
Journal: Circulation Research (1954)

The zero of potential of the electrical field produced by the heart beat is defined and measured as the average value over the surface of a large spherical, integrating electrode which contains the subject and a homogeneous conducting medium. The Zero of potential thus defined is apparently free of assumptions of any kind and is used to evaluate the error on the three-branch and the four-branch central terminal with equal resistances. The latter may, in certain instances, be brought to zero by using unequal resistances. The potential function at its electrodes is that of an unweighted resultant vector or a point dipole. The electrodes which contribute to its potential are remote.
Peptide Receptors as Molecular Targets for Cancer Diagnosis and Therapy
Authors: Jean Claude Reubi
Journal: Endocrine Reviews (2003)

During the past decade, proof of the principle that peptide receptors can be used successfully for in vivo targeting of human cancers has been provided. The molecular basis for targeting rests on the in vitro observation that peptide receptors can be expressed in large quantities in certain tumors. The clinical impact is at the diagnostic level: in vivo receptor scintigraphy uses radiolabeled peptides for the localization of tumors and their metastases. It is also at the therapeutic level: peptide receptor radiotherapy of tumors emerges as a serious treatment option. Peptides linked to cytotoxic agents are also considered for therapeutic applications. The use of nonradiolabeled, noncytotoxic peptide analogs for long-term antiproliferative treatment of tumors appears promising for only a few tumor types, whereas the symptomatic treatment of neuroendocrine tumors by somatostatin analogs is clearly successful. The present review summarizes and critically evaluates the in vitro data on peptide and peptide receptor expression in human cancers. These data are considered to be the molecular basis for peptide receptor targeting of tumors. The paradigmatic peptide somatostatin and its receptors are extensively reviewed in the light of in vivo targeting of neuroendocrine tumors. The role of the more recently described targeting peptides vasoactive intestinal peptide, gastrin-releasing peptide, and cholecystokinin/gastrin is discussed. Other emerging and promising peptides and their respective receptors, including neurotensin, substance P, and neuropeptide Y, are introduced. This information relates to established and potential clinical applications in oncology.
Differential Diagnosis of Hypercalcemia-Reply
Authors: Edward T. Wong
Journal: JAMA (1982)

<h3>In Reply.—</h3> Mr Bertini suggests that asking the question about a history of taking drugs that can cause hypercalcemia much earlier than decision 4 would save the patient "the pain and risks of multiple venipunctures and the costs of the concomitant laboratory tests." Let us consider how the algorithm might be applied to a patient with drug-induced hypercalcemia. Decision 1 asks for two tests, a serum calcium value and a serum protein electrophoresis, to avoid investigation of spurious hypercalcemia. Decision 2 asks whether there is a present or past history of carcinoma. Decision 3 asks whether hypercalcemia has been documented for more than one year in the patient's medical record and whether there are symptoms compatible with primary hyperparathyroidism, such as kidney stones or peptic ulcer. For drug-induced hypercalcemia, the questions in decisions 2 and 3 would most likely be answered negatively simply on the basis of only the history
High-Tech Medicine in the Caribbean
Authors: Robert N. Ubell
Journal: New England Journal of Medicine (1983)

When Cuban guerrilla bands fought in remote mountain villages more than a quarter of a century ago, one of their first promises was to provide Cubans with medical care equal to any in the world. Today, on the eve of the silver anniversary of the "triumph of the revolution," even Cuba's detractors admit that the new government has made good on that commitment. Although in certain respects Cuba's revolutionaries started with a nation somewhat less medically deprived than other Third World countries, Cubans still suffered the punishment of poverty and neglect. Now the island has emerged in such good health . . .
ACE Gene I/D Polymorphism and Sarcoidosis Pulmonary Disease Severity
Authors: DEIRDRE S. McGRATH, PATRICK J. FOLEY, MARTIN PETREK, LYDIE IZAKOVICOVA-HOLLA, VITEZSLAV DOLEK, SRIHARI VEERARAGHAVAN, PENELOPE A. LYMPANY, PANAGIOTIS PANTELIDIS, ANNA VASKU, ATHOL U. WELLS, KENNETH I. WELSH, ROLAND M. DU BOIS
Journal: American Journal of Respiratory and Critical Care Medicine (2001)

Previous studies of the insertion/deletion (I/D) polymorphism of the angiotensin-converting enzyme (ACE) gene in sarcoidosis have revealed both ethnic heterogeneity of I/D frequencies and controversy surrounding the association between the polymorphism and severity of disease. The objective of this study was, therefore, to clarify the role of the ACE I/D polymorphism in (1) disease susceptibility, (2) pulmonary disease severity (with particular reference to pulmonary fibrosis), and (3) pulmonary disease progression, in two distinct European sarcoidosis populations. Standard chest radiographic staging was performed on 118 UK and 56 Czech white patients with sarcoidosis at 2 yr from presentation. Pulmonary function data were analyzed, and patients were then categorized according to disease severity. A PCR-SSP assay was used to determine the ACE I/D genotype of each patient studied. The I/D allele frequencies from these patients were compared with frequencies from ethnically matched UK (n = 386) and Czech (n = 179) control subjects using a chi-square contingency table. No significant differences were seen in the distribution of the ACE I/D genotypes, allele frequencies or phenotype frequencies. Furthermore, no association was found between the ACE I/D polymorphism and pulmonary disease severity, fibrosis, and progression. We conclude that the ACE I/D polymorphism has no role in sarcoidosis susceptibility in European whites and that it is not a regulatory variant in this disease.Keywords: ACE; polymorphism; susceptibility gene; sarcoidosis; ethnicity
Gene therapy for severe combined immunodeficiency: are we there yet?
Authors: Marina Cavazzana-Calvo, Alain Fischer
Journal: Journal of Clinical Investigation (2007)

Inherited and acquired diseases of the hematopoietic system can be cured by allogeneic hematopoietic stem cell transplantation. This treatment strategy is highly successful when an HLA-matched sibling donor is available, but if not, few therapeutic options exist. Gene-modified, autologous bone marrow transplantation can circumvent the severe immunological complications that occur when a related HLA-mismatched donor is used and thus represents an attractive alternative. In this review, we summarize the advantages and limitations associated with the use of gene therapy to cure SCID. Insertional mutagenesis and technological improvements aimed at increasing the safety of this strategy are also discussed.
The effects of topical doxepin on responses to histamine, substance P and prostaglandin E<sub>2</sub>in human skin
Authors: R.A. SABROE, C.T.C. KENNEDY, C.B. ARCHER
Journal: British Journal of Dermatology (1997)

The tricyclic antidepressant, doxepin, is known to have H1 and H2 antihistaminic effects. Recently, 5% doxepin cream has been marketed in the U.S.A. for treatment of eczematous dermatoses. We investigated the effects of topical doxepin treatment on histamine-, substance P- and prostaglandin E2- (PGE2) induced responses in the skin of normal and atopic subjects. We compared the effects of topical doxepin with those of the oral antihistamine terfenadine. The weal volume and flare area responses to histamine were significantly reduced by treatment with topical doxepin or oral terfenadine in both normal and atopic subjects (P < 0.05). The mean +/- SEM percentage reduction in flare area for 10 micrograms/site of histamine in non-atopics and atopics was 48 +/- 8% and 60 +/- 17% with terfenadine, and 54 +/- 12% and 81 +/- 4% with topical doxepin, respectively. The mean percentage reduction in weal volume for the same dose of histamine in non-atopics and atopics was 70 +/- 9% and 63 +/- 16% with terfenadine, and 96 +/- 2% and 89 +/- 6% with topical doxepin, respectively. The flare but not the weal response to substance P was inhibited by both treatments in all subjects (P < 0.05). The mean +/- SEM percentage reduction in flare area for 200 pmol/site of substance P in non-atopics and atopics was 53 +/- 10% and 73 +/- 4% with terfenadine, and 74 +/- 7% and 75 +/- 4% with topical doxepin, respectively. The cutaneous responses to PGE2 were not affected by either drug. The inhibitory effects of doxepin were as great as those of terfenadine, and doxepin had a significantly greater effect than terfenadine in inhibiting the weal response to histamine and flare response to substance P in normal volunteers (P < 0.05). There was no significant difference between atopics and non-atopics in the percentage reduction of cutaneous responses by oral terfenadine or topical doxepin. Marked sedation occurred in three of the first 10 subjects treated with topical doxepin, necessitating a reduction in dosage for the remaining six subjects. In summary, topical doxepin was as effective as, and sometimes more effective than, a standard dose of oral terfenadine in the inhibition of histamine-induced and axon-reflex-mediated cutaneous responses. The marked sedative effect may limit its clinical use in some patients.
Adult Thymus Contains FoxN1− Epithelial Stem Cells that Are Bipotent for Medullary and Cortical Thymic Epithelial Lineages
Authors: Ahmet Ucar, Olga Ucar, Paula Klug, Sonja Matt, Fabian Brunk, Thomas G. Hofmann, Bruno Kyewski
Journal: Immunity (2014)

Within the thymus, two major thymic epithelial cell (TEC) subsets-cortical and medullary TECs-provide unique structural and functional niches for T cell development and establishment of central tolerance. Both lineages are believed to originate from a common progenitor cell, yet the cellular and molecular identity of these bipotent TEC progenitors/stem cells remains ill defined. Here we identify rare stromal cells in the murine adult thymus, which under low-attachment conditions formed spheres (termed "thymospheres"). These thymosphere-forming cells (TSFCs) displayed the stemness features of being slow cycling, self-renewing, and bipotent. TSFCs could be significantly enriched based on their distinct surface antigen phenotype. The FoxN1 transcription factor was dispensable for TSFCs maintenance in situ and for commitment to the medullary and cortical TEC lineages. In summary, this study presents the characterization of the adult thymic epithelial stem cells and demonstrates the dispensability of FoxN1 function for their stemness.