tbuckley/cabot-search huggingface dataset:
Nonlinear (amplified) relationship between nuclear occupancy by triiodothyronine and the appearance rate of hepatic alpha-glycerophosphate dehydrogenase and malic enzyme in the rat.
Authors: J H Oppenheimer, P Coulombe, H L Schwartz, N W Gutfeld
Journal: Journal of Clinical Investigation (1978)

Three separate approaches were applied to examine the general relationship between R, the rate of induction of specific enzymes (mitochondrial alpha-glycero-phosphate dehydrogenase and cytosolic malic enzyme) and q, the fractional nuclear occupancy by triiodothyronine in male Sprague-Dawley rats. Daily 200-microgram injections of triiodothyronine per 10u g body wt for 7 days resulted in saturation of the hepatic nuclear sites and the achievement of an apparent new steady state of enzyme levels. The increase achieved over base-line hypothyroid levels was then compared with the increment over hypothyroid base line characteristic of intact euthyroid animals with 47% of nuclear sites occupied. The maximal theoretical reate of steady-state enzyme induction could be protected on the basis of the observed maximal increase in enzyme activity observed 1 day after the injection of graded doses of hormone and lambda, the known fractional rate of enzyme dissipation. The 24-h dose-response studies were used to generate R as a continuous function of q, both in hypothyroid as well as in euthyroid animals. This approach involved the numerical solution of an ordinary differential equation describing the rate of change of enzyme as a function of R, which was assumed to be uniquely related to q. Results of these analyses indicated that the ratio of the maximal rate of induction of enzyme at full occupancy to the rate of induction under euthyroid conditions assumes a value between 9.0 and 19.5, depending on the precise analytic and experimental approach applied. This value is far in excess of the theoretical ratio 2.13 which on would anticipate if R were linearly related to q and 47% of the nuclear sites occupied under physiological conditions. Thus, the signal for enzyme induction appears to undergo progressjive amplification with increasing nuclear occupancy. Moreover, the curve describing the relationship between R and q appears highly nonlinear throughout (concave upwards). Although the molecular mechanism responsible for amplification is unknown, recognition of this phenomenon may be helpful in understanding tissue effects of thyroid hormone excess. Moreover, the analytic technique for determining R as a function of q may be of general applicability in studying hormonal response systems under nonsteady-state conditions.
Sulfonylrea Treatment in Permanent Neonatal Diabetes Due to G53D Mutation in the <i>KCNJ11</i> Gene
Authors: Lucimary C. Gurgel, Felipe Crispim, Maria Helena S. Noffs, Erich Belzunces, Marcio A. Rahal, Regina S. Moisés
Journal: Diabetes Care (2007)

Previous studies have reported the successful switch from insulin to sulfonylrea therapy in some patients who have neonatal diabetes due to KCNJ11 mutations (1); however, data on adults are limited (2,3). Also, it has not yet been determined whether neurological symptoms can be improved by the action of sulfonylrea therapy.

Here, we report the glycemic and neurological responses in an adult patient with the G53D mutation in the KCNJ11 gene who was transferred from insulin to sulfonylurea.

A 26-year-old male patient was diagnosed with diabetes in the third month of …
Topical methyl aminolaevulinate photodynamic therapy for treatment of facial acne vulgaris: results of a randomized, controlled study
Authors: C. Hörfelt, J. Funk, M. Frohm-Nilsson, D. Wiegleb Edström, A-M. Wennberg
Journal: British Journal of Dermatology (2006)

Background There is a need for alternative treatments for moderate to severe acne vulgaris. Preliminary experience suggests that topical methyl aminolaevulinate photodynamic therapy (MAL‐PDT) may have potential. Objectives To investigate the efficacy and tolerability of MAL‐PDT for treatment of moderate inflammatory facial acne. Patients/methods Thirty patients aged 15–28 years with moderate to severe acne were included in a blinded, prospective, randomized, placebo‐controlled multicentre study. Each side of each patient's face was randomly assigned to treatment with MAL (160 mg g−1) or placebo cream, applied for 3 h prior to illumination. A second treatment was given 2 weeks later. On each occasion, patients assessed the intensity of pain using a 10‐cm visual analogue scale. Inflammatory and noninflammatory acne lesions were counted at baseline and 4 and 10 weeks after the last PDT treatment. The investigator assessed the global severity of acne at baseline (seven patients had severe acne on at least one side of the face) and each study visit using a six‐point rating scale. Data were analysed on an intention‐to‐treat basis, including all 30 patients. Results There was a statistically significant greater reduction in the total inflammatory lesion count with MAL‐PDT compared with placebo PDT at week 12; median reduction 54% [95% confidence interval (CI) 35–64%] vs. 20% (95% CI 8–50%), P = 0·0006. MAL‐PDT was associated with more pain than placebo PDT, although intensity varied across centres and was reduced with repeated treatment. Local adverse events were consistent with this treatment modality. Conclusions MAL‐PDT is effective in the treatment of moderate to severe inflammatory facial acne. Further studies are warranted to optimize this promising procedure.
Complete Response From Thalidomide in Angiosarcoma After Treatment of Breast Cancer
Authors: Vinod Raina, Manju Sengar, Nootan K. Shukla, Sankaranavamsam S. Deo, Bidhu K. Mohanty, Dayanand Sharma, Ruma Ray, Prasenjit Das, Goura K. Rath
Journal: Journal of Clinical Oncology (2007)
Fibroblast Contractility
Authors: HIROYUKI MIKI, TADASHI MIO, SONOKO NAGAI, YUMA HOSHINO, TAISHI NAGAO, MASANORI KITAICHI, TAKATERU IZUMI
Journal: American Journal of Respiratory and Critical Care Medicine (2000)

The aim of this study was to compare the function of lung fibroblasts obtained from surgically biopsied specimens of patients with idiopathic pulmonary fibrosis/usual interstitial pneumonia (UIP; n = 5), nonspecific interstitial pneumonia (NSIP; n = 5), and normal parts of surgically resected lungs (control; n = 5). The results showed that (1) fibroblasts obtained from UIP showed increased contractility compared with those obtained from NSIP or controls (UIP, 72.7 ± 6.21%; NSIP, 32.8 ± 5.46; controls, 28.5 ± 3.51, p < 0.01 in UIP versus NSIP or control); (2) this increase in contractility was consistent with enhanced F-actin content in fibroblasts; (3) conditioned media from UIP fibroblast cultures enhanced control fibroblast contractility, whereas those obtained from NSIP or controls did not; (4) the 180 and 25 kD products representing the contractility in conditioned media were identified as fibronectin (ED-A domain) and TGF- β 1 by immunoblots, respectively; (5) the UIP-conditioned media contained higher amounts of fibronectin or TGF- β 1 (fibronectin: UIP 289 ± 47.1 ng/ml, NSIP 121 ± 23.0, control 118 ± 16.0; TGF- β 1: UIP 798 ± 119 pg/ml, NSIP 246 ± 69.1, control 247 ± 53.6, p < 0.01 in UIP versus NSIP or control); (6) the contractility positively correlated with the amount of either fibronectin (r = 0.867, p < 0.001, n = 15) or TGF- β 1 (r = 0.939, p < 0.001, n = 15), respectively. Thus, UIP fibroblasts showed greater contractility than did NSIP fibroblasts and upregulated control fibroblasts.
β-Papillomaviruses and psoriasis: an intra-patient comparison of human papillomavirus carriage in skin and hair
Authors: J.G. Cronin, D. Mesher, K. Purdie, H. Evans, J. Breuer, C.A. Harwood, J.M. McGregor, C.M. Proby
Journal: British Journal of Dermatology (2008)

Human papillomaviruses (HPVs) of the beta genus (beta-PV), especially HPV5 and HPV36, are proposed to play a pathogenic role in psoriasis, but many previous studies have failed to control for potential confounders, including treatment.To re-examine the relationship between beta-PV and psoriasis addressing limitations present in previous studies and analyse intra-patient concordance for carriage of HPV.Plucked eyebrow hairs and forearm skin scrapes were collected from 20 newly diagnosed, previously untreated adult patients with psoriasis and 23 normal controls. A combination of type-specific and degenerate polymerase chain reaction methods was used to achieve comprehensive HPV DNA detection.The prevalence of HPV in hair and skin from psoriasis patients was higher than in controls (83.3% vs. 46.7%, respectively, P < 0.03 corrected for age and clustering). HPV5 or HPV36 were not over-represented. The profile of diverse beta-PV types was comparable in the two groups. Intra-patient concordance for HPV DNA at separate sites was high (P < 0.00001).Our data do not support a specific causal role for HPV5 or HPV36 in psoriasis, but suggest that psoriatic skin may be more permissive for viral presence than normal skin. High intra-patient concordance for specific HPV types at separate sites, together with the ubiquity of HPV DNA in normal human skin, suggests that an individual becomes colonized with a particular beta-PV profile presumably to the exclusion of other types. To what extent this HPV profile is then causal in the subsequent development of hyperproliferative skin disease is unknown.
The Cost of Topical Drugs for Dermatophyte Infections
Authors: S. Elizabeth Whitmore
Journal: JAMA (1995)

To the Editor.  —The article by Drs Chren and Landefeld 1 was very good; however, the authors should note that clotrimazole is now available over the counter (Lotrimin AFR, Mycelex OTCR, as well as store brands). Twenty-four to 30-gram tubes of these products can be purchased in local drug stores in Baltimore, Md, for $7 to $15.  It may be that the most cost-effective way for a physician to treat dermatophyte infections not involving scalp and nails is with the recommendation of an over-the-counter clotrimazole product, as well as a prescription for a different antifungal cream if the skin does not clear within a month. Finally, it is important for the physician to recommend further followup or referral to a dermatologist if the prescription cream is also unsuccessful in clearing the infection. Potassium hydroxide wet mount or fungal culture of skin scale, skin biopsy, or patch testing for allergic contact
Does delta infection play a part in the pathogenesis of hepatitis B virus related hepatocellular carcinoma?
Authors: M C Kew, G M Dusheiko, S J Hadziyannis, A Patterson
Journal: BMJ (1984)

1727 clinical findings, but this did not alter management.Of the 60 patients in category 2 with abnormal radiographs, 57 had clinical evidence of cardiorespiratory disease.in B-viral induced hepatocellular carcinoma.Cancer (in press).
Expression of interferon alfa signaling components in human alcoholic liver disease
Authors: Van-Anh Nguyen, Bin Gao
Journal: Hepatology (2002)

Interferon alfa (IFN-α) is currently the only well-established therapy for viral hepatitis. However, its effectiveness is much reduced (&lt;10%) in alcoholic patients. The mechanism underlying this resistance is not fully understood. In this study, we examined the expression of IFN-α signaling components and its inhibitory factors in 9 alcoholic liver disease (ALD) and 8 healthy control liver tissues. In comparison with normal control livers, expression of IFN-β, IFN-α receptor ½, Jak1, and Tyk2 remained unchanged in ALD livers, whereas expression of IFN-α, signal transducer and activator of transcription factor 1 (STAT1), and p48 were up-regulated and expression of STAT2 was down-regulated. Expression of antiviral MxA a karyophilic 75 kd protein induced by IFN in mouse cells carrying the influenza virus resistance allele Mx + and 2'-5' oligoadenylate synthetase (OAS) proteins was not regulated, whereas expression of double-stranded RNA-activated protein kinase (PKR) was decreased by 55% in ALD livers. Three families of inhibitory factors for the JAK-STAT signaling pathway were examined in ALD livers. Members of the suppressor of cytokine signaling (SOCS) family, including SOCS 1, 2, 3, and CIS, and the protein tyrosine phosphatases, including Shp-1, Shp-2, and CD45, were not up-regulated in ALD livers, whereas the phosphorylation of and protein levels of p42/44 mitogen-activated protein kinase (p42/44MAP kinase) were increased about 3.9- and 3.2-fold in ALD livers in comparison with normal control livers, respectively. In conclusion, these findings suggest that chronic alcohol consumption down-regulates STAT2 and PKR, but up-regulates p42/44 mitogen-activated protein kinase (p42/44MAP kinase), which may cause down-regulation of IFN-α signaling in the liver of ALD patients.
Enterovenous Fistulization in Crohn's Disease
Authors: Leopold Reiner
Journal: JAMA (1978)

A case of Crohn's disease was complicated by enterovenous fistulization (ileum to superior mesenteric vein) with septic manifestations. The fistulization was diagnosed by the observation of gas in the liver and by the opacification of mesenteric veins following a barium meal. (<i>JAMA</i>239:130-132, 1978)
THERAPEUTIC ACTION OF N-PHENYLGLYCINEAMIDE-p-ARSONIC ACID (TRYPARSAMIDE) UPON EXPERIMENTAL INFECTIONS OF TRYPANOSOMA RHODESIENSE
Authors: Louise Pearce, Wade H. Brown
Journal: The Journal of Experimental Medicine (1921)

A series of experiments was carried out to determine the effects of tryparsamide upon the infections produced in various species of animals by Tr. rhodesiense. The strain of trypanosome used was one which possessed a very low virulence for guinea pigs, was fairly virulent for mice and rats, and highly virulent for rabbits. Therapeutic experiments carried out on 24 hour infections in mice and rats showed that cures could be obtained in this class of infections by the administration of a single large dose of the drug amounting to approximately two-thirds of the maximum tolerable dose, as contrasted with similar results in cases of gambiense infections from approximately one-ninth and one-fifth of this dose respectively. With advanced infections in rabbits, there appeared to be no single dose of the drug capable of insuring a cure which could be administered with safety, although some cures were obtainable with doses approximating the maximum tolerable dose. Treatment of these infections could be carried to a successful conclusion, however, by an intensive system of treatment in which large doses of the drug were administered at short intervals of time, and even relapses yielded to this treatment in some instances. The employment of such a method of treatment was possible on account of the unusual tolerance exhibited by animals to this drug, a fact which was previously emphasized.
Concepts in Anesthesiology
Authors: Vincent J. Collins
Journal: JAMA (1963)

<h3>To the Editor:</h3> —Since there is essential agreement with regard to Dr. Sherman's letter, it is only necessary to make some further comments. With respect to the matter of inferiority complex that is prevalent in the specialty of anesthesiology, perhaps it is more likely a matter of motivation or intrinsic laziness. At any rate, too many anesthesiologists are content with a cursory visit, if any at all, prior to administration of the anesthetic followed by its technical administration and very little postoperative medical care. This is the easy way out and it must be halted. I am in perfect agreement that we must accept equal responsibility for the care of the patient during the surgical experiences. To have equal responsibility, however, we must have knowledge, skills, and judgement consistent with the responsibility. These too are lacking in many of our colleagues. Surgeons want first-class internists labeled anesthesiologists to help them,
Abstract P4-03-08: Pathological analysis of intraductal papillary lesions in 3690 patients
Authors: Z Xu, W Xing, Z Yang, Q Li, Y Gu, Y Zhang
Journal: Cancer Research (2013)

Abstract Background:Papillary lesions of the breast (PL) account for 1 - 2% in breast tumors and 10% in benign tumors. Ductoscopy due to its high rate (60 times) amplification and visualization of lesions, which makes it possible to directly visualize the duct from the orifice of the duct well into the periphery. It could not only find abnormities which other tests could not provide, but also predict histological diagnosis.However, ductoscopy findings and pathological results are not always consistent. Ductoscopy examine is limited by many factors such as complicated anatomical structure of breast and ductal obstruction, so in some cases it may have missed diagnosis. Lesions could be missed due to extrusion and shedding during ductoscopy examine procedure and preparation of pathological section. Methods:In this study, we retrospectively studied on 4170 papillary lesions diagnosed by ductoscopy in 3690 patients from April 23, 2008 to October 31st, 2012 and compared incidence of each disease. These cases were evaluated by final histopathology(42.2% solitary papillary lesion, 32.5% multiple papillomatosis, 13.0% premalignant or malignant lesions, 6.5% mammary duct or plasma cell mastitis, 5.7% epithelial hyperplasia). The sensitivity of ductoscopy for PL in this study was 87.8%, and specificity was 89.2%. Results and Discussion:Spontaneous nipple discharge(SND) is the third third most common presenting symptom of breast disease accounting for 3∼8% of breast symptoms. But in our experience, not all of the intraductal lesions would have SND, especially in those cases which localized more distally. Besides, intraductal lesions in premalignant or malignant lesions cases would have more incidence to localize distally than their benign papilloma. Thus, if we only take ductoscopy on patients who suffer SND, we might have some missed diagnosis for those people who did not suffer SND including malignant lesions.At present, although ductoscopy is not routine examination for breast cancer screening, we consider that for people who share a high-risk of developping breast cancer, although she might not have SND, ductoscopy could be a selective screen tool. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P4-03-08.
Science, medicine, and the future: Microbial genome sequencing---beyond the double helix
Authors: P. J Jenks
Journal: BMJ (1998)

Considerable advances in automated DNA sequencing and bioinformatics have made the sequencing of entire microbial genomes a reality (see fig 1). Researchers have been quick to recognise the scientific value of microbial sequence data, and there is now a frantic rush to sequence a wide range of important micro-organisms. The continuing release of data from these projects, combined with advances in techniques used to investigate pathogenesis, will lead to an unprecedented understanding of micro-organisms and how they cause disease.

In this article I discuss how this sequence information will affect the practice of clinical microbiology and the management of infectious diseases. In particular, I examine how the large scale study of the entire genetic complement of micro-organisms should result in the provision of more rapid and efficient diagnostic techniques, as well as the development of new antimicrobial strategies.

In the past few years a large number of clinically important bacteria, parasites, and fungi have been sequenced, and genomic data for many human pathogens will be available by the turn of the century (see box). Because many of the early sequencing efforts were funded by private industry, concerns were raised about ownership and freedom of access to the data generated by these projects. As sequencing technology has become more refined and efficient, however, the cost of such projects has fallen, and funding is increasingly being provided by government agencies and medical charities. This has greatly improved access to microbial sequence information, and data from most projects are deposited, often on a daily basis, on websites on the internet.

A comprehensive catalogue of all genome sequencing projects is provided by the Magpie Genome Sequencing Project List (www.mcs.anl.gov), and links to individual projects are also available at this site. Other useful resources include the website of the Institute for Genomic Research (www.tigr.org), which …
Abstract 5233: MicroRNA in biofluid as robust biomarkers for cancer
Authors: Thorarinn Blondal, Anni Thomsen, Jörg Krummheyer, Peter Mouritzen, Ditte Andreasen, Maria Theilum, Jan Stenvang, Claus L. Andersen, Hans J. Nielsen, Nils Brünner
Journal: Cancer Research (2014)

Abstract microRNAs constitute a class of small cellular RNAs (typically 19-23 nt) that function as post-transcriptional regulators of gene expression. Current estimates indicate that more than one third of the human cellular transcriptome is regulated by this small class of RNA (∼2000 miRNA). The study of extracellular microRNAs and their potential as pathophysiological markers has greatly expanded in the last couple of years. microRNAs have been shown to be actively exported from tissues into the circulation through a variety of mechanisms including exosome and microvesicle transport, and complexing with RNA binding proteins or HDL. The high relative stability of microRNAs in common clinical source materials (FFPE blocks, plasma, serum, urine, saliva, etc.) and the ability of microRNA expression profiles to accurately classify discrete tissue types and specific disease states have positioned microRNAs as promising new biomarkers for diagnostic application in cancer. We have applied Exiqons highly sensitive LNA™-based qPCR platform for detection of microRNAs, which has enabled microRNA profiling in biofluids where levels are extremely low. The platform uses a single RT reaction to conduct full miRNome profiling and allows high-throughput profiling of microRNAs without the need for pre-amplification. Thousands of biofluid samples including serum/plasma and urine have been profiled to determine normal reference ranges for circulating microRNAs as well as to identify biomarkers of disease. Extensive data qualification and analysis methods have been developed and are central parameters to secure high quality data from biofluids. The methods can quickly and robustly be applied in biomarker discovery and validation projects. We will present examples from our collaborative cancer diagnostic projects. Also we have developed a new exosome enrichment method and will present a comparison of microRNA profiles obtained with this method to profiles obtained with different commercial available exosome isolation methods and standard profiles of whole plasma and serum. Citation Format: Thorarinn Blondal, Anni Thomsen, Jörg Krummheyer, Peter Mouritzen, Ditte Andreasen, Maria Theilum, Jan Stenvang, Claus L. Andersen, Hans J. Nielsen, Nils Brünner. MicroRNA in biofluid as robust biomarkers for cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 5233. doi:10.1158/1538-7445.AM2014-5233
BACK STRAIN AND SCIATICA
Authors: FRANK R. OBER
Journal: JAMA (1935)

It is my purpose in this paper to present a new theory relating to the cause of lame backs. The members of the profession at large know only too well that there are many symptoms of low back disabilities for which there have been no explanations. The terms sacro-iliac strain and dislocation or lumbosacral strain are in common use. Up to the present, these explanations have satisfied most physicians, depending on which side of the fence they happen to be. When roentgenograms of the sacro-iliac and lumbosacral joints are presented which show no evidence in this region of any pathologic condition, either congenital or acquired, it would seem difficult to make a positive diagnosis of either sacro-iliac or lumbo-sacral strain. One is frequently troubled by the fact that there is a negative roentgenogram of a patient whose clinical signs and symptoms are those of extreme irritation in the sacro-iliac or