tbuckley/cabot-search huggingface dataset:
Biliary cholesterol secretion by the twinned sterol half-transporters ABCG5 and ABCG8
Authors: Henning Wittenburg, Martin C. Carey
Journal: Journal of Clinical Investigation (2002)

The long wait for a cellular and functional definition of canalicular transporters for biliary cholesterol appears to be over. Articles in this issue of the JCI provide a fascinating account of the cellular itinerary of two murine ATP-binding cassette (ABC) half-transporters from the ribosome to the hepatocyte apical membranes (1) and show that the corresponding human genes, when overexpressed in transgenic mice, can greatly augment cholesterol secretion into bile (2).

This field was opened with the genetic solution (3, 4) to the enigma of a disease commonly known as sitosterolemia (5, 6). This autosomal recessive disorder of lipid metabolism is characterized by an accumulation of plant sterols, including sitosterol, in the plasma of patients with this disease and is therefore also known as phytosterolemia. Normally, the intestinal absorption of sitosterol and other unwanted plant sterols is dwarfed by the absorption of cholesterol, and the absorbed phytosterols are cleared from the body by highly efficient secretion into bile (5). However, patients with sitosterolemia display intestinal hyperabsorption of plant sterols and impaired biliary sterol secretion, leading to accumulation of phytosterols in the body (6). The metabolism of cholesterol is altered in the same manner, but to a lesser extent (5), rendering many patients hypercholesterolemic (6) and prone to xanthomas and premature atherosclerosis (5, 6). The dramatic consequences of this rare disease demonstrate the importance of a finely tuned mechanism for restricting the absorption and accumulation of ingested sterols. The underlying pathophysiological defects indicated that unraveling the molecular basis of sitosterolemia might shed light on important principles concerning intestinal sterol absorption as well as cholesterol secretion into bile.

Two independent groups (3, 4) identified mutations in sitosterolemia patients in either member of an adjacent pair of genes, ABCG5 and ABCG8, encoding ABC transporters expressed in the liver and intestine (3, 4, 7). Functional ABC transporters consist of 12 membrane-spanning domains and two ATP-binding sites, whereas ABCG5 and ABCG8 are examples of half-transporters containing only six transmembrane domains and one ATP-binding site. Therefore, both teams of investigators (3, 7) suggested that ABCG5 and ABCG8 function as a heterodimer to limit intestinal sterol absorption by effluxing sterols from enterocytes to small intestinal lumen and by promoting hepatic sterol secretion into bile. Still, in the absence of direct evidence, the function of ABCG5 and ABCG8 and their subcellular localization remained hypothetical until now.
Open Fracture—Dislocation of the Ankle
Authors: Otto E. Aufranc
Journal: JAMA (1961)

Dr.E. T.Wyman Jr.: This 44-year-old woman was injured 20 minutes before admission. She said she had been struck by an automobile and had not been unconscious. There was marked lateral displacement of the right foot at the ankle. The right tibia protruded through a 4-cm. transverse skin laceration located approximately 3 cm. above the tip of the medial malleolus. Articular cartilage of the distal tibia was visible. The medial malleolus had been sheared off just below the level of the joint. There was a small amount of dirt present in the wound. The dorsalis pedis pulse was present and bounding. No defect of sensory or motor nerve function was demonstrated. There were no other injuries, and her general condition was good. After initial evaluation in the emergency ward, an intravenous infusion was started, and blood specimens were sent for cross-matching. After appropriate skin testing had been done, 3,000
Institutionalizing Madness: Families, Therapy, and Society
Authors: Charles Kent Smith
Journal: JAMA (1990)

The heart of this book is a review of the treatment of several families, mostly from various kibbutzim, followed over a period of time. Most had chronic problems, had had intensive psychological therapy, and then were seen in consultation by Dr Minuchin when he was visiting in Israel. An intervention was made that was discussed in some detail, and often long-term follow-up was available. These cases follow an introductory chapter focusing on deinstitutionalizing the treatment of patients with emotional problems. There is a strong focus on the problems inherent in having providers from different disciplines with different frameworks and different explanatory models, and how these different views impact on treatment. The description in the preface that "in the end, the book has become a study of the partial and culture-bound way the mental health field responds to people labeled 'patients'" is an accurate description. The book is interesting, and the
Band 3 Courcouronnes (Ser667Phe): a trafficking mutant differentially rescued by wild-type band 3 and glycophorin A
Authors: Ashley M. Toye, Rosalind C. Williamson, Moudji Khanfar, Brigitte Bader-Meunier, Thérèse Cynober, Madeleine Thibault, Gil Tchernia, Michèle Déchaux, Jean Delaunay, Lesley J. Bruce
Journal: Blood (2008)

We describe a mutation in human erythrocyte band 3 (anion exchanger 1; SLC4A1) causing both hereditary spherocytosis and distal renal tubular acidosis. The proband developed a transfusion-dependent, hemolytic anemia following birth. Immunoblotting showed band 3 was reduced to approximately 35% of wildtype; other proteins of the band 3/Rh macrocomplex were also reduced. DNA sequence analysis revealed a novel homozygous mutation, c.2000C>T, leading to the amino acid substitution Ser667Phe. The parents were heterozygous for the same mutation. Sulfate influx in the patient's erythrocytes was approximately 40% wild type. The mutant band 3 produced very little chloride influx when expressed in Xenopus oocytes. Influx was partially rescued by coexpression of glycophorin A and also rescued by coexpression of wild-type band 3. At 2 years of age, an ammonium chloride challenge showed the child has incomplete distal renal tubular acidosis (dRTA). Stable expression of mutant kidney band 3 in both nonpolarized and polarized Madin-Darby canine kidney cells showed that most of the mutant protein was retained in the endoplasmic reticulum. Overall our results suggest that the Ser667Phe does not affect the anion transport function of band 3, but causes a trafficking defect in both erythrocytes and kidney cells.
EU-US trade treaty threatens vital health gains, warn public health experts
Authors: M. Limb
Journal: BMJ (2015)

A study of peak flow variability was carried out among a population sample of 63 wheezy children aged 9-11 years. Recordings were made over 12 days at three times during the day--first thing in the morning, on returning home from school and at bedtime. Eighty nine per cent of the children had symptoms during the diary period. The mean amplitude (difference between the highest and lowest daily peak flow values) was 17% of the mean daily value (range 4-48%). By cosinor analysis the amplitude was 12% of the mean value (range 1-53%). In 65% of the children the lowest point of the daily rhythm as determined by cosinor analysis lay between midnight and 8am; the rhythm was, however, statistically significant in only fourteen individuals (22%). These levels of variability are considerably lower than those previously reported in hospital based studies of adult asthmatics. As a method of demonstrating variable airflow obstruction, which is the defining physiological characteristic of asthma, the use of a peak flow diary alone appears to be of limited value in children.
Abstract 4225: PNA mediated real-time PCR clamping assay to detect IDH1 mutations .
Authors: Jihye Yoon, jae jin Choi, Woohyung Choi, Heekyung Park
Journal: Cancer Research (2013)

Abstract The hotspot mutations in codon 132 of isocitrate dehydrogenase 1 (IDH1) is a frequent DNA alteration in gliomas and astrocytomas. IDH mutations are prognostic and diagnostic for tumors with mutation, associated with a proneural subclass, and have longer survival compared with those without the mutation. We have developed a highly sensitive and simple method to detect hotspot mutations in codon 132 of IDH1 using PNA-mediated real-time PCR clamping, PNAClampTM. PNAClampTM is based on unique properties of PNA probes that PNA oligomers are not recognized by DNA that can serve as sequence-selective clamps during PCR amplification. This method can also detect 5 mutations through only one tube reactions simultaneously, which requires only 10 ng of the target DNA each. Data analysis was much faster and easier to perform than analysis of the sequencing data, and results could be obtained in 3hr from DNA extraction to analysis. Furthermore, we could readily identify a mixture of 1% mutant allele vs. 99% wild type allele with our PNAClamp assay, in comparison to direct sequencing assay which have detection limit of approximately 20% mutant allele. We performed the assay on 191 paraffin-embedded glioma specimens in Korea for diagnosing IDH mutation. The results showed that the PNAClampTM IDH1 detected higher number of mutation (27.2%, 52/191) than of direct sequencing (20.9%, 40/191) in 191 giloma samples in Korea. The result was not in agreement with the sequencing in12 (6.3%) samples. This result was likely due to the high sensitivity of PNAClampTM. PNAClampTM is a fast, sensitive and easy to perform method which can reliably detect common mutations of IDH genes in gliomas or other tumors. Citation Format: Jihye Yoon, jae jin Choi, Woohyung Choi, Heekyung Park. PNA mediated real-time PCR clamping assay to detect IDH1 mutations . [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4225. doi:10.1158/1538-7445.AM2013-4225
Inhibition of gastrin gene expression by somatostatin.
Authors: P S Karnik, S J Monahan, M M Wolfe
Journal: Journal of Clinical Investigation (1989)

Previous studies performed in this laboratory have demonstrated somatostatin-containing cells in close proximity to gastrin cells in antral mucosa and have shown that somatostatin exerts a local regulatory effect on gastrin release. The present studies were directed to determine whether the effects of somatostatin on the antral gastrin cell involve pretranslational events. The effects of somatostatin on gastrin mRNA were determined by dot blot hybridization using a gastrin antisense RNA probe derived from human gastrin cDNA. Inclusion of somatostatin in the incubation medium caused a dose-dependent inhibition of steady-state gastrin mRNA. Conversely, when antral somatostatin was neutralized by the addition of specific somatostatin antibodies to the incubation medium, gastrin mRNA levels increased by 116 +/- 31% over control values (P less than 0.01). Northern blot hybridization of total antral RNA demonstrated a single major band with a molecular size of approximately 620 nucleotides, closely matching the predicted size of gastrin mRNA. The effect of somatostatin on the rate of gastrin gene transcription was examined using nuclear run-off transcription assays. Inclusion of antibodies to somatostatin in the incubation medium resulted in a 33.8 +/- 3.3% increase in gastrin gene transcriptional activity (P less than 0.01). These studies indicate that, in addition to its established effect on peptide release, somatostatin exerts inhibitory effects on antral gastrin cells at the pretranslational level. Although this inhibition appears to occur in part at the gene transcriptional level, the results also indicate that somatostatin may affect posttranscriptional processing of gastrin mRNA.
Observations on Chloramines as Nasal Antiseptics
Authors: E. K. Dunham, H. D. Dakin
Journal: BMJ (1917)

contracture of the tendo Achillis.Marked hyperaesthesia to cottoil-wool stimulation on the sole aild on the outer side of the foot.Fi1fth Operation.-Division of tendo Achillis and forcible ex- 'tension of the knee with the hope of stretching nerve fibres and diminishing pain.Scar was felt to stretch in the popliteal apace.Slight alleviation of pain for two days, but it recurre(l.Sixth Operation (May 24th).-Removal of scar, freeing nerve and fascial "1 sleeve."Both popliteal nerves were found sur- rounded by large areas of fibrous tissue.Both nerves were freed from scar as much as possible, and this extended for 3 irl.above their junction.The n-erves felt hard and fibrous, but to such an extent that further treatment seemned contrainIdicated.Fascial sheaths taken from both thighs 6 in.bv 2 in.; invested both popliteals an(d the sciatic like a pair of trousers.All three nerves inijected with 5 c.cn. normal saline above and belowv the "sleeves."Temporary relief was obtained for a week but the pain afterwards recurred.June 18th.Pain as before and foot oedematous.July 4th.As patient continues to lose weight and is very depressed it was decided to sacrifice the " sciatic " nerve.This on account of the length of time the patient has been in bed (fifteen months), although there is voluntary power in extension of the ankle.Sevenzth Operation (Jully 6th).-Excision of sciatic nerve at the junction.Four inches removed, which included repair work of operation No. 6, with fascial covering.July 10th.All pain gone; anaesthesia in foot.September 19th.Patient invalided to Canada;, boot and iron to prevent drop-foot.solvents.A study of the germicidal action of these bodies will be found in the Proc.llnvt.Sbc., B, 89, p. 232, 1916.-t It may be worth noting that Captain Sweet and Dr. L,ee, at our suggestion, have invrestigated the use of a timnilar mDixture containingX 5-per cent. of dichloramine-T as a surgical dressing for infected wounds.
Role of Coronary Artery Lumen Enlargement in Improving Coronary Blood Flow After Balloon Angioplasty and Stenting: A Combined Intravascular Ultrasound Doppler Flow and Imaging Study
Authors: Morton J Kern, Patrick Dupouy, John H Drury, Frank V Aguirre, Eduardo Aptecar, Richard G Bach, Eugene A Caracciolo, Thomas J Donohue, Jean-Luc Dubois Rande, Herbert J Geschwind, Carol J Mechem, Ghanshyam Kane, Emannuel Teiger, Thomas L Wolford
Journal: Journal of the American College of Cardiology (1997)
Abstract 676: Substrate specificity and inhibitors of histone lysine HMTase NSD1, NSD2/MMSET/WHSC1, and NSD3/WHSC1L1.
Authors: Eric Di Luccio, Masayo Morishita
Journal: Cancer Research (2013)

Abstract The nuclear receptor binding SET domain proteins (NSDs) is a family of three histone-lysine N-methyltransferases, NSD1, NSD2/MMSET/WHSC1, and NSD3/WHSC1L1. The NSDs are oncogenes. The amplification of NSD1 has been reported in multiple myeloma, lung cancer, neuroblastomas and glioblastomas. The amplification of either NSD1 or NSD2 triggers the cellular transformation to cancer formation. NSD2 is associated with tumor aggressiveness or prognosis in most types of cancers including prostate cancer and multiple myeloma and is overexpressed in at least 15 different cancers. Increased NSD2 activity was reported in tumor proliferation in glioblastoma multiforms and myeloma, resulting in aberrantly high global levels of H3K36me2. NSD3 is involved in lung cancer and found amplified in breast cancer cell lines and primary breast carcinomas. The abnormal NSD1-NUP98 and NSD3-NUP98 fusions increase H3K36 methylation, leading to acute myeloid leukemia. Although the NSD proteins are instrumental in the development of numerous cancers, their mechanisms of action in this context remain unclear. However, it appears that consequently increased H3K36 methylation by deregulated NSDs concomitant with decreased H3K27 methylation is perhaps one of the underlying mechanisms that alter gene expression profiles. In this study, we defined the molecular determinants of the recognition of histone marks by the NSDs to provide medicinal chemistry insights into the design of selective and specific NSDs inhibitors. Our data highlights the catalytic versatility of NSD1, NSD2, and NSD3 in regulating the epigenome. Our results propose the first molecular models of the binding of 6-mer peptides H3K4 a.a.1-7; H3K9 a.a.5-11; H3K27 a.a.23-29; H3K36 a.a.32-38; H3K79 a.a.75-81; H4K20 a.a.16-22 with the catalytic domain of the NSDs. Exploiting this data, we derived a virtual ligand screening strategy to identify inhibitors targeting NSD1, NSD2 and NSD3. In vitro, using recombinant NSDs-SET purified enzyme, we performed H3K36me1 inhibitory assays with the top candidates. Here for the first time, we report the discovery of a small subset of NSD inhibitors (namely LEM-xx) that do not violate the empirical Lipinski's rule of five, have a wcLogP &amp;lt; 3 and a total polar surface area &amp;lt;90 A**2. Citation Format: Eric Di Luccio, Masayo Morishita. Substrate specificity and inhibitors of histone lysine HMTase NSD1, NSD2/MMSET/WHSC1, and NSD3/WHSC1L1. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 676. doi:10.1158/1538-7445.AM2013-676 Note: This abstract was not presented at the AACR Annual Meeting 2013 because the presenter was unable to attend.
Dose-response testing with nickel sulphate using the TRUE testR in nickel-sensitive individuals. Multiple nickel sulphate patch-test reactions do not cause an "angry back"
Authors: K.E. ANDERSEN, C. LIDEN, J. HANSEN, A. VOEUND
Journal: British Journal of Dermatology (1993)

Journal Article Dose‐response testing with nickel sulphate using the TRUE test® in nickel‐sensitive individuals. Multiple nickel sulphate patch‐test reactions do not cause an “angry back” Get access K.E. ANDERSEN, K.E. ANDERSEN Department of Dermatology, Odense University Hospital, Odense, Denmark Correspondense: Dr. K. E. Andersen, Department of Dermatology, Odense University Hospital, DK‐5000, Odense, Denmark. Search for other works by this author on: Oxford Academic Google Scholar C. LIDEN, C. LIDEN Department of Occupational Dermatology, Karolinska Hospital, and National Institute of Occupational Health, Stockholm, Sweden Search for other works by this author on: Oxford Academic Google Scholar J. HANSEN, J. HANSEN Kebi Pharmacia, Hillrod Denmark Search for other works by this author on: Oxford Academic Google Scholar A. VØEUND A. VØEUND NOVO Research Institute, Bagsværd, Denmark Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 129, Issue 1, 1 July 1993, Pages 50–56, https://doi.org/10.1111/j.1365-2133.1993.tb03311.x Published: 01 July 1993 Article history Accepted: 28 January 1993 Published: 01 July 1993
Activation of Mitochondrial K <sub>ATP</sub> Channel Elicits Late Preconditioning Against Myocardial Infarction via Protein Kinase C Signaling Pathway
Authors: En Takashi, Yigang Wang, Muhammad Ashraf
Journal: Circulation Research (1999)

Abstract —Activation of mitochondrial K ATP (mitoK ATP ) channel induces acute ischemic preconditioning (PC) against ischemic injury. The ability of this channel to elicit late PC remains unknown. The present study tests the hypothesis that stimulation of mitoK ATP channel induces late PC via the protein kinase C (PKC) signaling pathway. Rats were subjected to 30 minutes of regional ischemia and 120 minutes of reperfusion (I/R). In other groups, rats were pretreated with diazoxide, a specific opener of the mitoK ATP channel (7 mg/kg, IV), 12, 24, 48, and 72 hours before they were subjected to I/R. A maximum reduction in infarct size was observed after 24 hours (33.3±2.2% versus I/R group, 62.1 ±2.4%). Pretreatment with diazoxide did not reduce the infarct size significantly after 12, 48, and 72 hours (50.2±4.3%, 50.5±4.6%, and 58.2±4.9%) compared with the I/R group. The protection was blocked with 5-hydroxydecanoic acid (5-HD, 5 mg/kg IV), a relatively selective mitoK ATP channel blocker (56.5±2.7%), and chelerythrine (5 mg/kg IV), an effective PKC inhibitor (57.1±3.4%) administered either on the first day before diazoxide pretreatment or 10 minutes before I/R on the second day. Cell necrosis was decreased by ≈50% in the diazoxide preconditioned hearts compared with control I/R hearts. Cell death by apoptosis was also significantly decreased in diazoxide pretreated hearts (3.2%) as compared with I/R (11.3%). In conclusion, activation of mitoK ATP channel with diazoxide produces late PC against reperfusion injury. The effect of mitoK ATP channel appears to be dependent on the PKC-mediated signal pathway.
"The Fitness Factory," Part I: The Psychiatrist's Role in Determining Competency
Authors: ROBERT LLOYD GOLDSTEIN
Journal: American Journal of Psychiatry (1973)

This article is the first in a series on the work of the New York City Forensic Psychiatry Clinic, which performs mental competency evaluations of defendants appearing before the New York City Criminal Court. The author describes the clinic's philosophy regarding competency and contrasts its roles before and after the enactment of the new Criminal Procedure Law that granted considerably broader powers to the clinic.
Lipid‐Conjugation of Endogenous Neuropeptides: Improved Biotherapy against Human Pancreatic Cancer
Authors: Gopakumar Gopalakrishnan, Sinda Lepetre, Andrei Maksimenko, Simona Mura, Didier Desmaële, Patrick Couvreur
Journal: Advanced Healthcare Materials (2015)

Neuropeptides are small neuronal signaling molecules that act as neuromodulators for a variety of neural functions including analgesia, reproduction, social behavior, learning, and memory. One of the endogenous neuropeptides-Met-Enkephalin (Met-Enk), has been shown to display an inhibitory effect on cell proliferation and differentiation. Here, a novel lipid-modification approach is shown to create a small library of neuropeptides that will allow increased bioavailability and plasma stability after systemic administration. It is demonstrated, on an experimental model of human pancreatic adenocarcinoma, that lipid conjugation of Met-Enk enhances its tumor suppression efficacy compared to its nonlipidated counterparts, both in vitro and in vivo. More strikingly, the in vivo studies show that a combination therapy with a reduced concentration of Gemcitabine has suppressed the tumor growth considerably even three weeks after the last treatment.
Colonoscopic finding of an unusual sigmoid colon fistula caused by ovarian teratoma
Authors: Hang Yi, Yi Mou, Wei Liu, Hongze Zeng, Qiming Wang, Chengwei Tang, Bing Hu
Journal: Endoscopy (2015)

A 42-year-old woman was admitted to our hospital because of intermittent lower abdominal pain with mild constipation over the preceding 4 months. Her medical history was uneventful and we recommended that she undergo a colonoscopy. During the procedure, we discovered to our surprise a fistula in the colon (16 cm from the anal verge near the rectosigmoid junction) with swollen surrounding mucosa and a tuft of hair that was protruding straight into the colonic lumen ([Fig. 1]; [Video 1]). Our endoscopic diagnosis was of a fistula of the sigmoid colon with the suspicion of an underlying teratoma. An abdominal computed tomography (CT) scan revealed a heterogeneous left ovarian mass in close contact with the sigmoid colon ([Fig. 2]).