tbuckley/cabot-search huggingface dataset:
Vasopressin-induced disruption of actin cytoskeletal organization and canalicular function in isolated rat hepatocyte couplets: Possible involvement of protein kinase C
Authors: Marcelo G. Roma, Vicki Stone, Robert Shaw, Roger Coleman
Journal: Hepatology (1998)

The effect of vasopressin (VP) on canalicular function and hepatocellular morphology, with particular regard to actin cytoskeletal organization and the concomitant plasma membrane bleb formation, was studied in isolated rat hepatocyte couplets. VP induced the concentration-dependent formation of multiple plasma membrane blebs as well as simultaneous impairment in both canalicular vacuolar accumulation (cVA) and retention (cVR) of the fluorescent bile acid, cholyl-lysyl-fluorescein (CLF), which evaluate couplet secretory function and tight-junction integrity, respectively. These effects were mimicked by the protein kinase C (PKC) activator, phorbol dibutyrate (PDB), but not by the protein kinase A (PKA) activator, dibutyryl-cAMP. VP-induced bleb formation and canalicular dysfunction were fully prevented by the protein kinase inhibitor, H-7, but not by the PKA inhibitor, KT5720, further suggesting a specific role of PKC. VP-induced alterations were also prevented by pretreatment with the Ca 2+ -buffering agent, BAPTA/AM, but not with the calmodulin-dependent protein kinase II antagonist, calmidazolium. Neither the Ca 2+ -activated neutral protease inhibitor, leupeptin, nor the antioxidants, α-tocopherol or deferoxamine, were able to prevent either VP-induced plasma membrane blebbing or canalicular dysfunction. The Ca 2+ -ionophore, A23187, mimicked the VP-induced alterations, but its harmful effects were completely prevented by H-7. Bleb formation induced by VP and PDB was accompanied by an extensive redistribution of filamentous actin from the pericanalicular area to the cell body, and this effect was fully prevented by H-7. These results suggest that VP-induced canalicular and cytoskeletal dysfunction is mediated by PKC and that classical (Ca 2+ -dependent) PKC appear to be involved because intracellular Ca 2+ is required for VP to induce its harmful effects.
Clinical Features of a Previously Undescribed Codon 216 (proline to serine) Mutation in the Peripherin/Retinal Degeneration Slow Gene in Autosomal Dominant Retinitis Pigmentosa
Authors: Gerald A. Fishman, Edwin Stone, Leonardo D. Gilbert, Kimberlie Vandenburgh, Val C. Sheffield, John R. Heckenlively
Journal: Ophthalmology (1994)
A theme issue by, for, and about Africa
Authors: Catherine Senyimba, Edmund Mwebesa, Siobhan Kennelly, Karen Frame, Richard Harding
Journal: BMJ (2005)

A theme issue by, for, and about Africa Results from Ugandan programme preventing maternal transmission of HIVEditor-Since the efficacy of antiretroviral drugs in preventing HIV transmission from mother to child was first shown, much effort has been devoted in many countries in Africa to implement sustainable regimens. [1]2][3][4] To identify potential reasons affecting uptake we evaluated the five year performance of a programme at St Francis Hospital Nsambya in Kampala, Uganda.The programme included voluntary counselling and confidential HIV testing for pregnant women and administration of antiretroviral prophylaxis in the peripartum period (zidovudine or nevirapine) for HIV positive women.Overall 24 133 women received counselling, 76% (18 384) agreed to be tested, and 2011 (10.9%) were HIV positive; 1341 (66.7% of the HIV positive women) were enrolled in the programme and received antiretroviral drugs.Acceptance of the test increased from 72.7% (9103/12 524) in 2000-2 to 79.9% (9281/11 609) in 2003-4, when a drug access programme became available in the hospital.Acceptance of the test and enrolment in the programme were lower in married or cohabitating women (test acceptance rate 72.9% (7735/10 605)) than single women (78% (860/1106)), indicating that the fear of being identified as HIV positive in the family is still a strong limiting factor and that men could have an important role.Acceptance of the test was lower in women belonging to the local tribe in Kampala (Baganda), probably because of fear of being recognised by hospital health workers.Higher education was associated with a lower prevalence of HIV and a higher enrolment in the programme, confirming that education can have a key role not only in protecting against HIV but also in allowing HIV positive people to benefit from existing measures against the spread of HIV.
Abstract 3481: Dietary acetate supplementation as a means of inducing glioma stem cell growth arrest
Authors: Patrick M. Long, Andrew Tsen, John R. Moffett, Aryan M. A. Namboodiri, Mariano S. Viapiano, Diane M. Jaworski
Journal: Cancer Research (2012)

Abstract Glioma, the most common primary brain tumor of the adult central nervous system, is associated with a poor prognosis due, in part, to the presence of chemoradiotherapy-resistant glioma stem-like cells responsible for inevitable post-surgical recurrence. N-acetyl-L-aspartate (NAA), one of the most concentrated metabolic sources of acetate in the brain, and aspartoacylase (ASPA), the enzyme responsible for NAA degradation, are significantly reduced in glioma tumors. NAA-derived acetate is converted to acetyl coenzyme A via acetyl-CoA synthetase (AceCS) for use in lipogenesis, protein/histone acetylation, and the TCA cycle. We propose that glyceryltriacetate (GTA), a FDA approved food additive with “generally regarded as safe” status, may be an effective means of reducing glioma growth via restoration of acetate levels. The effect of GTA on the growth of both established (Hs683, HOG) and stem-like (grade II OG33, grade III OG35) oligodendroglioma cell lines was assessed. In vitro, GTA induced growth arrest in all cells examined (i.e., increased proportion of cells in G0/G1 and reduced S phase cells by flow cytometry of propidium iodide labeled cells 24 hours after treatment and unbiased trypan blue exclusion based cytometry up to 5 days post-treatment). Growth arrest was not associated with apoptosis (lack of cleaved poly ADP-ribose polymerase immunolabeling), but differentiation (increased CNPase expression). ASPA expression was greater in stem-like cells when grown in stem cell media than differentiation media and was decreased in GTA-treated OG35 cells. Interestingly, GTA did not decrease ASPA expression in OG33 cells, but induced a novel 26 kDa ASPA isoform. ASPA and AceCS1 were co-localized within the nucleus. Nuclear, but not cytosolic, ASPA expression was decreased upon GTA addition in stem cell media, but not differentiation media. Finally, the effect of GTA on orthotopically grafted luciferase expressing OG33 and OG35 cells was assessed. Bioluminescence and tumor volume were reduced in GTA treated mice. These data suggest that the nuclear ASPA/AceCS1 co-localization provides acetate for histone acetylation to maintain cells in a progenitor/stem-like state and that decreased ASPA promotes gliomagenesis. Inasmuch as infants with Canavan Disease, a leukodystrophy due to ASPA mutation, treated with high dose GTA showed no significant side effects, GTA may prove an effective therapy to prevent recurrence by inducing growth arrest/differentiation of glioma stem-like cells. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3481. doi:1538-7445.AM2012-3481
Melanoma specific protein: occurrence in the urine of patients with halo naevus and vitiligo
Authors: K.B. COOKE, CLAIRE BENNETT, R.C.D. STAUGHTON
Journal: British Journal of Dermatology (1978)

Melanoma specific protein is immunologically related to altered naevus cell cytoplasm. It is excreted by patients with malignant melanoma but in no other malignancy. The protein has been detected in patients with actively developing halo naevi but not when repigmentation is taking place. It also occurs in patients with very active vitiligo but in no other pigment condition we have studied. It is suggested that the protein is a marker of active destruction of naevus cells by immune mechanisms and that the release of toxic materials during this immune reaction may be responsible for the production of the halo phenomenon and for the areas of vitiligo that may be seen elsewhere on the skin.
Ulceroglandular Tularemia Treated with Streptomycin
Authors: Raymond E. Lesser, Sidney Miller
Journal: New England Journal of Medicine (1948)

HEILMAN'S1 demonstration of the effectiveness of streptomycin against Pasteurella tularensis in vitro and in vivo has found application in the treatment of tularemia in man. The cases presented below are considered to be of interest because they report additional experience with the use of streptomycin in the treatment of tularemia. Furthermore, they afford an interesting comparison of the effectiveness of treatment of the acute and chronic phases of the disease.Case ReportsCase 1. A 39-year-old man was hospitalized on February 14, 1947, complaining of "cold sensations," pain in the eyes and back and coughing and sneezing of 2 days' . . .
Somatostatin is required for masculinization of growth hormone–regulated hepatic gene expression but not of somatic growth
Authors: Malcolm J. Low, Veronica Otero-Corchon, Albert F. Parlow, Jose L. Ramirez, Ujendra Kumar, Yogesh C. Patel, Marcelo Rubinstein
Journal: Journal of Clinical Investigation (2001)

Pulsatile growth hormone (GH) secretion differs between males and females and regulates the sex-specific expression of cytochrome P450s in liver. Sex steroids influence the secretory dynamics of GH, but the neuroendocrine mechanisms have not been conclusively established. Because periventricular hypothalamic somatostatin (SST) expression is greater in males than in females, we generated knockout (Smst–/–) mice to investigate whether SST peptides are necessary for sexually differentiated GH secretion and action. Despite marked increases in nadir and median plasma GH levels in both sexes of Smst–/– compared with Smst+/+ mice, the mutant mice had growth curves identical to their sibling controls and retained a normal sexual dimorphism in weight and length. In contrast, the liver of male Smst–/– mice was feminized, resulting in an identical profile of GH-regulated hepatic mRNAs between male and female mutants. Male Smst-/- mice show higher expression of two SST receptors in the hypothalamus and pituitary than do females. These data indicate that SST is required to masculinize the ultradian GH rhythm by suppressing interpulse GH levels. In the absence of SST, male and female mice exhibit similarly altered plasma GH profiles that eliminate sexually dimorphic liver function but do not affect dimorphic growth.
Hannah's Heirs: The Quest for the Genetic Origins of Alzheimer's Disease
Authors: T. Marteau
Journal: BMJ (1994)

Daniel A Pollen Oxford University Press, pounds sterling 16.95, pp 296 ISBN 0-19-506809-2

During a six week period in the autumn of 1992, three research groups independently published their discovery of the link between the abnormal gene for familial Alzheimer's disease and the long arm of chromosome 14. Daniel Pollen, a neurologist, tells his story of this discovery, starting with a visit to his surgery, seven years earlier, of a member of one of the largest known families affected by familial Alzheimer's disease.

The personal tragedy of Jeff's diagnosis was tempered by the pedigree that he had brought with him. The family was documented back to the birth of …
Intravenous Zanamivir for Oseltamivir-Resistant 2009 H1N1 Influenza
Authors: Aditya H. Gaur, Bindiya Bagga, Subrata Barman, Randall Hayden, Aubrey Lamptey, James M. Hoffman, Deepa Bhojwani, Patricia M. Flynn, Elaine Tuomanen, Richard Webby
Journal: New England Journal of Medicine (2009)

To the Editor: A 10-year-old girl with acute lymphoblastic leukemia was transferred to our hospital on August 31. The patient required mechanical ventilation for worsening lobar pneumonia, despite the administration of broad-spectrum antibiotics (for details, see the Supplementary Appendix, available with the full text of this letter at NEJM.org). Two weeks earlier, she had completed 5 days of oseltamivir for an upper respiratory tract infection caused by influenza A virus (with positive results on rapid antigen testing). On August 27, she had presented with lobar pneumonia (with negative results on rapid antigen testing). On admission to our hospital, infection with . . .
Successful Excision of a Left Ventricular Hamartoma
Authors: FLOYD R. PARKS, FORREST ADAMS, WILLIAM P. LONGMIRE
Journal: Circulation (1962)

A case of a 2-year-old child with a large hamartoma of the left ventricular wall is presented. The excision of the tumor is described, and a 2-year follow-up is given. Primary cardiac tumors should be suspected in patients with unexplained cardiac failure, unexplained cardiac arrhythmias, intracardiac calcifications, irregular shadows on x-ray, or symptoms and murmurs that change with position. Angiocardiography is suggested for diagnosis. Technical problems at operation involve the maintenance of satisfactory cardiac function and valve competence.
Treatment of Heart Failure with Spironolactone — Trial and Tribulations
Authors: John J.V. McMurray, Eileen O'Meara
Journal: New England Journal of Medicine (2004)

The application of evidence based on the results of clinical trials is a key aim of modern medical practice. Viewed from that perspective, the findings of Juurlink and colleagues in this issue of the Journal (pages 543–551) could be considered encouraging. The Randomized Aldactone Evaluation Study (RALES) showed that, when added to standard treatment (including an angiotensin-converting–enzyme [ACE] inhibitor), a low dose of the aldosterone antagonist spironolactone reduced the risk of death by 30 percent over an average follow-up period of two years among carefully selected patients with current or recent heart failure of New York Heart Association (NYHA) functional . . .
An Unusual Complication Of Pacemaker Insertion
Authors: John M. Keshishian
Journal: JAMA (1967)

To the Editor:—  Unusual complications following insertion of a pacemaker have been reported in the literature. The following complication developed in a patient after a seemingly routine insertion of a pervenous electrode.  Report of a Case:—  A 75-year-old widow was transferred by air evacuation from Maxwell Air Field to the George Washington University Hospital. Approximately 8 days before she had sustained a fractured hip and was hospitalized for operative treatment of the fracture. However, as a complication of the operation, the patient sustained ventricular fibrillation and cardiac arrest. This was quickly corrected, but complete heart block then developed. She had previously suffered transient bouts of incomplete heart block on a number of occasions. Accordingly, a temporary pervenous electrode was passed via the right external jugular and impacted in the right ventricle. Suitable pacing was obtained by a batterypowered pulse generator. The orthopedic situation was resolving, and it was decided that
Longitudinal Study of Earthquake-Related PTSD in a Randomly Selected Community Sample in North China
Authors: Xiangdong Wang, Lan Gao, Naotaka Shinfuku, Huabiao Zhang, Chengzhi Zhao, Yucun Shen
Journal: American Journal of Psychiatry (2000)

This study longitudinally described rates of posttraumatic stress disorder (PTSD) in two groups with different levels of severity of exposure to an earthquake in North China. The effects of diagnostic criteria on the frequency of detected PTSD were also examined.Subjects were randomly sampled in two villages at different distances from the earthquake epicenter. A total of 181 and 157 subjects were assessed at 3 months and 9 months after the earthquake, respectively, for PTSD by using both DSM-IV and DSM-III-R criteria. The brief version of the World Health Organization Quality of Life Assessment and three subscales of the SCL-90-R were also administered at both assessment points.The village with a higher level of initial exposure to the earthquake and a higher level of postearthquake support had a lower frequency of PTSD than the village with a lower level of initial exposure and less postearthquake support. The rate of onset of DSM-IV PTSD within 9 months for the two villages was 19.8% and 30.3%, respectively. In both villages, the rate of onset of earthquake-related PTSD within 9 months was 24.2% by using DSM-IV criteria and 41.4% by using DSM-III-R criteria. The introduction in DSM-IV of a criterion requiring clinically significant distress or impairment in functioning for a diagnosis of PTSD was a major contributor to the lower rate of DSM-IV PTSD.PTSD may be as prevalent and persistent in disaster victims in China as in those elsewhere. Prompt and effective postdisaster intervention could mitigate the impact of initial exposure and reduce the probability of PTSD occurrence. Caution should be used in comparing rates of postdisaster PTSD identified by using different diagnostic criteria.
Improved methods of detection, and prognostic significance, of vascular invasion in breast cancer.
Authors: RA Mohammed, IO Ellis, AR Green, EC Paish, MS Gill, SG Martin
Journal: Cancer Research (2009)

Abstract Abstract #3010 Vascular invasion, encompassing both lymphovascular (LVI) and blood vascular invasion (BVI), influences breast cancer patient prognosis. We have previously shown, using an immunohistochemical approach to distinguish between LVI and BVI in a well characterized group of 177 consecutive paraffin-embedded specimens breast cancer patients (52 LN+ and 125 LN-), that VI was detected in 32% of specimens and that 96% of such VI were invasion of lymphatic vessels. The presence of LVI was significantly associated with the presence of metastasis, recurrence and worse disease free interval (DFI) and overall survival (OS). In multivariate analysis, LVI was an independent poor prognostic factor. This original study has been expanded by examining LVI, assessed by podoplanin staining, in 1000 LN-, early stage, breast cancers. In addition to verifying initial results showing the prognostic power of detection of LVI in early stage tumours, it also allowed an examination of LVI in histological and basal phenotypes to determine if the frequency of LVI influences prognosis in different breast cancer phenotypes.&amp;#x2028; LVI was detected in 212 (21% of specimens). The lowest LVI positivity was observed in tubular carcinoma (5.6%), followed by mucinous (7.1%) and atypical medullary (18.5%) types. The highest LVI positivity was detected in invasive carcinoma of no special type (26%). Tumours with basal phenotype were significantly associated with higher LVI (29%) compared with 19% in non-basal tumours P =0.002.&amp;#x2028; In the LVI-positive specimens; 203 (76%) specimens had peri-tumoural LVIs and 58 (24%) had an LVI in intra-tumoural vessels (9 specimens had LVIs in the intra-tumoural vessels only and 49 specimens had an LVI in both intra- and peri-tumoural vessels). The frequency of LVI ranged from 1 to 79: 167specimens (79%) had &amp;lt;5 LVIs, 23 (11%) had 6-10 LVIs and 22 (10%) had &amp;gt;10LVIs. There was no significant difference between the frequency of LVI and development of recurrence or death from the disease.&amp;#x2028; Patients with LVI had a significantly worse prognosis. The 20-year OS rate was 85% in patients without LVI compared with 68% in patients with LVI. In multivariate analysis for OS, tumour size (P =0.004), tumour grade (P&amp;lt; 0.0001), and LVI (P &amp;lt;0.0001) retained significance. However, for DFI, only LVI (P&amp;lt;0.0001) remained significant. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 3010.
Sulphonamide in the Treatment of Corneal Ulcer
Authors: A. Philipp, K. W. Stuart
Journal: BMJ (1941)

influence of an anaesthetic.Data are wanting by which the relative value of the different methods of handling a patient can be assessed.Treatment In addition to such points as have already been men- tioned note should be kept of all drugs given, the dose and time being recorded-for example, A.T.S., morphine, atropine, oxygen, sulphanilamide.A record should be kept of all fluids administered, whether by mouth, rectum, or vein.When blood or plasma is given the rate of trans-
Plasma Antithrombin III and Thrombin Generation Time: Correlation with Hemoglobin A1 and Fasting Serum Glucose in Young Diabetic Women
Authors: James R Sowers, Michael L Tuck, Pilek K Sowers
Journal: Diabetes Care (1980)

Three parameters of coagulability – thrombin generation time (TGT), antithrombin III (AT III), and activated partial thromboplastin time (ATPP) – and two parameters of diabetic control – serial measurements of fasting serum glucose (FG) and hemoglobin A1(HbA1) – were used to study the relationship between diabetic control and hypercoagulability. Four groups of females were studied consisting of 10 young normal, 10 young insulin-dependent diabetic, 10 pregnant nondiabetic, and 8 first-trimester, insulin-dependent, pregnant diabetic subjects. Fasting serum glucose values and HbA1 were higher (P &amp;lt; 0.005) in nonpregnant diabetic subjects (193.1 ± 29.1 mg/dl, 12.9 ± 1.1%) and pregnant diabetic subjects (111.0 ± 13.6 mg/dl, 8.2 ± 1.7%) than in controls (64.8 ± 4.4 mg/dl, 5.9 ± 0.1%) and the nondiabetic pregnant females (71.6 ± 3.8 mg/dl, 6.1 ± 0.2%). Young diabetic females, pregnant females, and pregnant diabetic subjects had a shorter (P &amp;lt; 0.01) TGT than did the controls. AT III was greater (P &amp;lt; 0.01) for controls (99.7 ± 2.7%) than for pregnant nondiabetic (83.2 ± 3.8%), diabetic (79.5 ± 2.5%), and pregnant diabetic subjects (76.2 ± 4–4%). There was a positive correlation (r = 0.88, P &amp;lt; 0.005) between HbA1 and FG in the 10 young diabetic and in the 8 pregnant diabetic subjects (r = 0.74, P &amp;lt; &amp;lt; 0.05). In the 10 diabetic females there was a negative correlation between AT III andFG(r = -0.76, P &amp;lt; 0.01) and between AT III and HbA1 (r = -0.79, P &amp;lt; 0.01). Thus, AT III is depressed in both diabetes and pregnancy, with pregnant diabetic subjects displaying the lowest AT III levels. Our observation that depression of AT III levels in young diabetic females was closely correlated with elevations of fasting serum glucose and HbA1 suggests that strict diabetic control may help prevent hypercoagulability in diabetes.