tbuckley/cabot-search huggingface dataset:
Core–Shell Hydrogel Microcapsules for Improved Islets Encapsulation
Authors: Minglin Ma, Alan Chiu, Gaurav Sahay, Joshua C. Doloff, Nimit Dholakia, Raj Thakrar, Joshua Cohen, Arturo Vegas, Delai Chen, Kaitlin M. Bratlie, Tram Dang, Roger L. York, Jennifer Hollister‐Lock, Gordon C. Weir, Daniel G. Anderson
Journal: Advanced Healthcare Materials (2012)

Islets microencapsulation holds great promise to treat type 1 diabetes. Currently used alginate microcapsules often have islets protruding outside capsules, leading to inadequate immuno-protection. A novel design of microcapsules with core–shell structures using a two-fluid co-axial electro-jetting is reported. Improved encapsulation and diabetes correction is achieved in a single step by simply confining the islets in the core region of the capsules.
Scar remodeling and transmural deformation after infarction in the pig.
Authors: J W Holmes, H Yamashita, L K Waldman, J W Covell
Journal: Circulation (1994)

BACKGROUND Changes in stress and tissue material properties have been proposed as important mechanical factors that may influence infarct expansion and subsequent healing. Because such changes will be reflected by alterations in the finite deformation of the tissue, we examined the direction and magnitude of myocardial deformation after coronary ligation in the pig. METHODS AND RESULTS Gold beads were implanted in the left ventricular free wall of five pigs. After ligation of the coronary supply to the region containing the markers, we used biplane cineradiography to reconstruct the three-dimensional deformations of the myocardium during single cardiac cycles as well as the remodeling deformations that occurred over time. Deformations were studied at 1 and 3 weeks after infarction. The analysis of single cardiac cycles revealed permanent loss of systolic shortening immediately after ligation. However, significant passive systolic wall thickening (P &lt; .001) and large shears were observed at 3 weeks in regions composed almost entirely of collagen. The analysis of remodeling deformations at 1 week revealed infarct expansion with a predominant axis that varied widely. At 3 weeks, a 30% to 60% reduction in local tissue volume was measured in the infarct region, with the principal direction of scar shrinkage nearly circumferential in all animals (range, -2 degrees to 35 degrees). CONCLUSIONS We conclude that infarct expansion and scar shrinkage may be controlled by different factors. In addition, we conclude that measurement of systolic wall thickening alone is not always adequate to assess postinfarction regional contractile function.
SIDELIGHTS ON THE PRACTICE OF MEDICINE IN THE PAST FROM EARLY ENGLISH LITERATURE
Authors: None Greenwood
Journal: BMJ (1915)

THE oriain of the meedical profession in this country is a disputed point.No literature thlrows much ligilt on thle subject, and thle earliest evidence of the practice of tile healing art in Enaland and Wales is thle existence of remains of medical instrumlents and appliances of the Roman period that liave been dug up in various places.For at least three centuries England and Wales was a settled Roman province, containing many large and prosperous cities, and enjoying a civilization equal to that of their sister cities on the Continent.We know from Roman sources that this civilization included all that was then known of medical and surgical science.We learn, too, from the Civil Law that there was a well recognized class or profession of Medici.The gleanings from old Roman remains in this country give ample evidence that these Medici came over lhere and carried on their profession.But in thle fifth century came the deluge of barbarous tribes from the north of Europe, sweeping away the whiole of Roman civilization, and witiL it no doubt most of the medical knowledge that up to that time had been enjoyed by the old population.After thle Saxon invasion, then, it would seem that medical and surgical science had to begin again, and it might be that our profession was slowly evolved de novo, possibly owing little or nothing to thle Roman civilization that had preceded it.Whether any of the Roman Medici survived the invasion and were enabled to carry on thleir art through the troublous times that followed and develop a sclhool at a more peaceful period is purely conjectural.But I cannot lhelp thlinking that we, like our sister pro- fession the law, may o-we much to that great people, whose influence in the civilization of the world has been so profound.Sir Lawrence Gomme has shown that in the case of London customs there are many old survivals from Roman sources, and he suggests that thle origin of our earliest lawyers must be looked for there.In The Village Community he says:Now the Ordler of the Coif (Serjeants-at-law) is the oldest association of lawyers in this country.There is no law for its first institution, nio charter from a sovereign, nothling to shew from whence, it sprinigs, except its remarkable parallel to Roman custom.If this custom coul(d be regarded as evidence, then our present K.C.'s can shew an unbroken descent from the Jurisier iti of ancient Rome.
Transfer of C3 Nephritic Factor from Mother to Fetus
Authors: Alvin E. Davis, Mohammed Amin Arnaout, Chester A. Alper, Fred S. Rosen
Journal: New England Journal of Medicine (1977)

Many patients with membranoproliferative glomerulonephritis and partial lipodystrophy have low levels of serum C3.1 2 3 4 Serum of these patients incubated with normal human serum may produce alternative-pathway-mediated cleavage of C3.5 6 7 The C3 cleaving activity has been ascribed to a serum protein called the C3 nephritic factor.5 6 7 Although nephritic factor has been purified and characterized as a unique serum protein,8 other evidence suggests that nephritic factor may be an immunoglobulin.9 A patient with partial lipodystrophy, who had high nephritic-factor titers and low serum C3 levels, became pregnant and thereby allowed study of transplacental transport of nephritic factor.Materials and Methods Serum specimens . . .
Neuropeptide PACAP in mouse liver ischemia and reperfusion injury: Immunomodulation by the cAMP-PKA pathway
Authors: Haofeng Ji, Yu Zhang, Xiu-da Shen, Feng Gao, Cynthia Y. Huang, Catalina Abad, Ronald W. Busuttil, James A. Waschek, Jerzy W. Kupiec-Weglinski
Journal: Hepatology (2012)

Hepatic ischemia and reperfusion injury (IRI), an exogenous antigen-independent local inflammation response, occurs in multiple clinical settings, including liver transplantation, hepatic resection, trauma, and shock. The immune system and the nervous system maintain extensive communication and mount a variety of integrated responses to danger signals through intricate chemical messengers. This study examined the function and potential therapeutic potential of neuropeptide pituitary adenylate cyclase-activating polypeptides (PACAP) in a murine model of partial liver “warm” ischemia (90 minutes) followed by reperfusion. Liver IRI readily triggered the expression of intrinsic PACAP and its receptors, whereas the hepatocellular damage was exacerbated in PACAP-deficient mice. Conversely, PACAP27, or PACAP38 peptide monotherapy, which elevates intracellular cyclic adenosine monophosphate/protein kinase A (cAMP-PKA) signaling, protected livers from IRI, as evidenced by diminished serum alanine aminotransferase levels and well-preserved tissue architecture. The liver protection rendered by PACAP peptides was accompanied by diminished neutrophil/macrophage infiltration and activation, reduced hepatocyte necrosis/apoptosis, and selectively augmented hepatic interleukin (IL)-10 expression. Strikingly, PKA inhibition readily restored liver damage in otherwise IR-resistant, PACAP-conditioned mice. In vitro , PACAP treatment not only diminished macrophage tumor necrosis factor alpha/IL-6/IL-12 levels in a PKA-dependent manner, but also prevented necrosis and apoptosis in primary mouse hepatocyte cultures. Conclusion: Our novel findings document the importance of PACAP-mediated cAMP-PKA signaling in hepatic homeostasis and cytoprotection in vivo . Because the enhancement of neural modulation differentially regulates local inflammation and prevents hepatocyte death, these results provide the rationale for novel approaches to manage liver inflammation and IRI in transplant patients. (Hepatology 2013)
Consultant Appointments and Medical Representation
Authors: G. C. Taylor
Journal: BMJ (1966)

falcipariem parasites were found in the blood after 19 months' stay away from a malarious zone.It is interesting to note that the patient in Walters's report was also five months pregnant.McGregor and Smith2 found that primigravidae seemed to lose immunity against P. falciparum, and Bruce- Chwatt3 observed an increased parasite density during parturition.These two cases tend to support the suggestion that pregnancy might predispose to clinical recrudescence of P. falciparuni malaria.In view of the com- plications associated with this infection great vigilance in detecting and treating it during the antenatal period is necessary.
The association of hepatic glycogen depletion with hyperammonemia in cirrhosis
Authors: Udaya M. Kabadi
Journal: Hepatology (1987)

Hyperammonemia is a well-recognized metabolic abnormality which occurs in cirrhotic patients with advanced liver dysfunction. We recently documented that hyperglucagonemia that occurs as a result of hepatic glycogen depletion may be responsible for this hyperammonemia by promoting gluconeogenesis to provide glucose as a fuel for functioning of several organ systems. Thus, hepatic glycogen depletion may be the initial process responsible for hyperammonemia. Since the glucose rise following intravenous glucagon administration is a reflection of hepatic glycogen breakdown, we studied the effect of glucagon (1 mg) injection on plasma glucose, insulin and ammonia levels after an overnight fast in cirrhotic patients and normal subjects. Glucose rise was significantly stunted, and ammonia rise was significantly greater in patients with advanced liver dysfunction as compared to normal subjects. Furthermore, the smaller the glucose increment, the earlier the ammonia rise. The smallest glucose responses were seen in the patients with the highest basal plasma ammonia levels. Finally, significant negative relationships were noted between the glucose response to glucagon administration (δglucose) and the degree of liver dysfunction as reflected by Composite Clinical Laboratory Index, as well as basal ammonia and ammonia responses (Δam-monia) on the other. Therefore, this study suggests that hepatic glycogen depletion may be the initial event leading to elevated plasma ammonia concentrations in hepatic cirrhosis.
Dendritic cell-lymphocyte clusters that form spontaneously in rheumatoid arthritis synovial effusions differ from clusters formed in human mixed leukocyte reactions.
Authors: V Tsai, N J Zvaifler
Journal: Journal of Clinical Investigation (1988)

Lymphocytes cluster about dendritic cells (DC) spontaneously in 48 h cultures of rheumatoid arthritis synovial fluid (RA SF) mononuclear cells and in peripheral blood autologous or allogeneic mixed leukocyte reactions. In the latter case, the clusters are predominantly CD4+ T cells (T4/T8 greater than 5) and with time progress in blastic cells that express IL-2 (Tac) and/or transferrin (T9) receptors. In contrast, the clusters in RA SF cultures have a T4/T8 ratio of less than 1 and a majority of the T8 cells coexpress the Leu 7 marker. T cells in these clusters remain inert and with time the clusters disintegrate. Addition of IL-1, IL-2, or IFN-gamma alone or in combination had no effect on RA SF clusters but T cells became blastic when exposed to 10% RA SF. Mixing experiments using RA SF DC with normal T cells and RA T cells with normal DC show that both RA SF DC and T cells are immunofunctional. In addition, clusters of RA SF from a patient with active tuberculosis proliferated vigorously to PPD. Therefore, the unique RA SF cluster profile may reflect the memory nature of the RA SF T cells resulting in a paucity of T cells that are responsive to autologous stimulation. However, an immunosuppressive role for the double-labeled (CD8 and Leu 7) cells has not been excluded.
Loss of Asxl1 leads to myelodysplastic syndrome–like disease in mice
Authors: Jiapeng Wang, Zhaomin Li, Yongzheng He, Feng Pan, Shi Chen, Steven Rhodes, Lihn Nguyen, Jin Yuan, Li Jiang, Xianlin Yang, Ophelia Weeks, Ziyue Liu, Jiehao Zhou, Hongyu Ni, Chen-Leng Cai, Mingjiang Xu, Feng-Chun Yang
Journal: Blood (2013)
Long-Term Experience With Isotope Cisternography
Authors: George J. Alker
Journal: JAMA (1972)

Isotope cisternography and ventriculography were performed on 106 patients with various neurological disorders. Both the normal cisternogram and the abnormal patterns were encountered in this series. Of 14 cases of cerebrospinal fluid rhinorrhea, all but two were correctly diagnosed. In 44 patients with communicating hydrocephalus, the tests were used as criteria for selecting those suitable for shunting procedures. Only a few abnormal cisternograms were encountered in a group of 25 children suspected of having compensated hydrocephalus. Fifteen patients with various shunts were observed with follow-up examinations to determine the patency and efficacy of the shunts. Isotope cisternography and ventriculography complemented the roentgenographic studies in determining the specific etiology of hydrocephalus in a small group of patients.
Tissue typing in brucellosis.
Authors: P T Dawes, S K Ghosh
Journal: Annals of the Rheumatic Diseases (1985)

The index case in this report was clinically, epidemiologically, and serologically proved to be suffering from acute brucellosis acquired in Britain and complicated by acute intractable reactive arthritis. HLA tissue typing was A1, A2, B7, and B27. As there is no information available about HLA typing in brucellosis in Britain, we examined further cases of human brucellosis retrospectively. Three further patients possessing B27 antigen were identified, only one of whom had had reactive arthritis. Eight of the 12 cases studied also carried A2, which is thus shown not to be protective against the development of brucellosis as had been suggested previously.
Five Years of Exemestane as Initial Therapy Compared to 5 Years of Tamoxifen Followed by Exemestane: The TEAM Trial, a Prospective, Randomized, Phase III Trial in Postmenopausal Women with Hormone-Sensitive Early Breast Cancer.
Authors: D. Rea, A. Hasenburg, C. Seynaeve, S. Jones, J. Vannetzel, R. Paridaens, C. Markopoulos, Y. Hozumi, H. Putter, E. Hille, L. Asmar, R. Urbanski, C. van de Velde, J. Bartlett, J. Smeets, D. Kieback
Journal: Cancer Research (2009)

Abstract Background: Exemestane (E) is a steroidal aromatase inhibitor (AI) with an established role in early breast cancer after 2–3 years of tamoxifen (T). Additionally, AIs have shown superiority to T as initial adjuvant therapy. The Tamoxifen Exemestane Adjuvant Multinational (TEAM) study has been prospectively designed to compare the role of E as initial adjuvant therapy with a sequential approach of T followed by E (T→E).Methods: Postmenopausal patients with hormone receptor–positive early breast cancer were randomized to open-label E 25 mg/d or T 20 mg/d. All patients completed surgery and chemotherapy, if indicated. Data were collected and analyzed by the Central Data Center in Leiden, The Netherlands. The trial was initiated in 2001 with the primary objective being a comparison of disease-free survival (DFS) with T vs E. In 2004, TEAM was modified in response to new data; all those initially receiving T were switched to E after 2.5–3 years. An additional 2500 patients were recruited and randomized at diagnosis to E or T→E for 5 years. The modified study design includes 2 coprimary endpoints: (1) DFS of T vs E that was previously reported at 2.75 years median follow-up (Jones S et al, abstract #15 presented at SABCS 2008); and (2) DFS at 5 years of E vs T→E that will be the focus of results presented here.Results: Between 2001 and January 2006, 9775 women were randomized to TEAM. In total, 99% of patients were ER+ and/or PgR+, 50% were node-negative, 44% underwent mastectomy, 68% received radiotherapy, and 36% received chemotherapy. In September 2009, median follow-up will be 5.5 years and the protocol-specified 1285 overall DFS events (locoregional or distant recurrence, second breast cancers, or death without recurrence) will have occurred, allowing for analysis of the second coprimary endpoint. We will present a detailed analysis of the 5-year results from theTEAM trial, the only prospectively powered randomized trial to compare 5 years of an initial AI vs T→AI, 2 commonly received adjuvant therapies for women with hormone receptor–positive early breast cancer. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 11.
73. Cats Produce a Potent CTL Response after Neonatal Gene Therapy That Can Be Blocked with CTLA4-Ig
Authors: Katherine P. Ponder, Baomei Wang, Ping Wang, Xiucui Ma, Ramin Herati, Bin Wang, Karyn Cullen, Patty O'Donnell, Tina M. Primeau, Mark E. Haskins
Journal: Molecular Therapy (2006)

Although gene therapy has reduced manifestations of genetic diseases, immune responses can abrogate the effect. One approach to induce tolerance is to perform gene transfer in newborns when the immune system is immature. This has allowed a therapeutic response to be achieved for lysosomal storage diseases and hemophilia in mice. However, it is unclear if this approach would be effective in large animals with more-mature immune systems at birth, and it is unlikely that this will be effective in humans. Immune responses will likely pose a tremendous hurdle for patients with null mutations, and identification of a large animal model with a sufficiently mature immune system at birth should facilitate preclinical studies to identify ways to block an expected immune response in humans. Gene therapy experiments were performed in mucopolysaccharidosis I (MPS I) cats, which are deficient in the lysosomal enzyme α-L-iduronidase (IDUA) due to a 3 bp deletion. An amphotropic retroviral vector (RV) expressing the canine IDUA was injected IV into newborn cats at 10(9) or 10(10) TU/kg. The canine protein differs from the feline protein at 130 positions of 653 aa. Expression can be followed by analysis of enzyme activity in serum, as some of the enzyme produced by cells is secreted into blood. Cats achieved high serum activity that averaged 286+/−416 (SD; N=7) U/ml and 2355+/−2763 (SD) U/ml at 1 month after gene transfer for the low and high RV dose, respectively. However, all animals lost expression by 3 months, which was associated with the development of cytotoxic T lymphocytes (CTLs) that could kill autologous cIDUA-expressing fibroblasts, and with a marked decrease in RV RNA sequences in the liver. In contrast, antibodies to cIDUA did not develop. In an attempt to block a CTL response, two cats were treated with the immunosuppressive agent CTLA4- Ig for 2 weeks around the time of transduction with the high dose of RV. CTLA4-Ig binds to CD80 or CD86, and prevents them from stimulating an immune response by activating CD28 on the surface of lymphocytes. These cats achieved 187+/−161 U/ml of IDUA activity in serum, which has been stable for 10 months to date, and did not develop a CTL response These data demonstrate that CTLA4-Ig can prevent a CTL response after neonatal gene therapy. Factors that reduce the efficiency of the immune system in newborn mice and/or humans include reduced secretion of cytokines by lymphocytes, and reduced levels of the co-stimulatory partners CD40 ligand and CD40. In contrast, lymphocytes from newborn humans have normal levels of CD80/CD86 and CD28. We hypothesize that the CD80/CD86 interaction with CD28 may be of particular importance in the newborn period in cats, explaining why transient CTLA4-Ig is so effective at inducing tolerance. The cat appears to be an excellent pre-clinical model for neonatal gene therapy.
Novel Use and Utility of Integrated Electronic Health Records to Assess Rates of Prediabetes Recognition and Treatment: Brief Report From an Integrated Electronic Health Records Pilot Study
Authors: Julie A. Schmittdiel, Sara R. Adams, Jodi Segal, Marie R. Griffin, Christianne L. Roumie, Kris Ohnsorg, Richard W. Grant, Patrick J. O’Connor
Journal: Diabetes Care (2013)

OBJECTIVE This study uses novel methods to examine the frequency of diagnosis and treatment of prediabetes in real-world clinical settings using electronic health record (EHR) data. RESEARCH DESIGN AND METHODS We identified a cohort of 358,120 adults with incident prediabetes (fasting plasma glucose [FPG] 100–125 mg/dL or glycated hemoglobin 5.7–6.4% [39–46 mmol/mol]) between 2006 and 2010 and examined rates of diagnosis and treatment in the 6 months after identification. RESULTS In the 6 months after identification of prediabetes, 18% of patients had their blood glucose levels retested; 13% received a physician diagnosis of prediabetes/hyperglycemia; 31.0% had prediabetes, diabetes, or lifestyle documented in the clinical notes; and &amp;lt;0.1% initiated metformin. Among patients with FPG 120–125 mg/dL, 31% were retested; metformin initiation remained &amp;lt;1%. CONCLUSIONS Documented rates of follow-up and treatment for prediabetes are low. EHR data may be a valuable tool to improve identification and treatment of prediabetes in the U.S.
Mechanisms of human eosinophil activation by complement protein C5a and platelet‐activating factor: similar functional responses are accompanied by different morphologic alterations
Authors: G. Zeck‐Kapp, C. Kroegel, U.N. Riede, A. Kapp
Journal: Allergy (1995)

The complement system is an important amplification system for the propagation of allergic as well as pseudoallergic inflammatory reactions. In the present study, the effect of the major anaphylatoxin C5a was compared with that of platelet‐activating factor (PAF) on highly purified eosinophils (≥95%) by functional as well as morphologic criteria. Upon stimulation with C5a, eosinophils maintained their spheric structure, developing short, pseudopodia‐like protrusions, whereas PAF induced the generation of a number of digitating protrusions. As shown by functional and ultrastructural assay systems, both stimuli provoked significant extracellular and intracellular H 2 O 2 production in eosinophils, which was inhibited by cytochalasin B. With C5a, a pronounced H 2 O 2 production was detected within the small cytoplasmic vesicles, whereas PAF‐induced H 2 O 2 production was observed on the outer surface of the plasma membrane in the contact zones between adjacent cells. Morphologic signs of degranulation induced by C5a and PAF were accompanied by the significantly increased release of eosinophil cationic protein and eosinophil peroxidase in the presence of cytochalasin B. Like PAF, C5a induced a significant production of reactive oxygen species in eosinophils. as measured by lucigenin‐dependent chemiluminescence (CL) responses in eosinophils. Maximal responses, comparable with those of interleukin‐5 (100 U/ml), were observed at concentrations of 10 5‐ ‐10 ‐6 and 10 ‐7 ‐10 ‐8 M for PAF and C5a, respectively. Separation of eosinophils by discontinuous density gradients revealed the existence of two hypodense eosinophil populations, one of them showing significantly reduced CL responses upon stimulation with C5a and PAF. In addition, CL responses upon stimulation with C5a and PAF were abrogated by cytochalasin B, staurosporine, and wortmannin, and were almost completely blocked by pertussis toxin. In conclusion, these data indicate that C5a induces events in human eosinophils comparable to those induced by PAF in the assay systems tested. Thus, C5a, generated after activation of the complement system, may be of major importance for the eosinophil activation observed in eosinophil‐related disease.