bluuebunny/crossref_metadata_2025_split huggingface dataset:
CONTRIBUTION TO THE PATHOGENESIS OF HEMOPHILIA
Authors: PAVLOVSKY ALFREDO 
Published: October 2019

Abstract
The causes of the delayed coagulation of hemophilic blood seem to become clearer as time advances. On one side we have the investigations of the school of Minot, indicating a deficit in the globulin fraction; and on the other side are the works of those who maintain that there exists an excess of anticoagulant substances. We support the latter theory, although in our opinion the two theories do not contradict each other, since it might be possible that this anticoagulant substance would act on the globulin fraction diminishing its coagulant power. This substance could be identified with the anticephalin fraction of Tocantins.
With the idea that this substance might be less stable than the coagulant fractions (fibrinogen, prothrombin, and thromboplastin) we have tried to render it inactive by keeping the blood in a refrigerator for a certain length of time. Inactivity was obtained in some of our experiments. We know that the stability of this substance varies from one patient to the other, but we have not been able to fix the cause of these variations.
In conclusion, we consider that other means of neutralizing the action of this anticoagulant substance should be investigated. This inactivity once obtained, we should have advanced far in solving the intricate problem of hemophilia.
THE PATHOLOGY OF INFECTIOUS MONONUCLEOSIS
Authors: CUSTER R. PHILIP , SMITH EDWARD B. 
Published: October 2019

Abstract
This pathologic study is based on 9 autopsies and many biopsies in cases of infectious mononucleosis.
The gross changes were almost exclusively confined to enlargement of lymphoid tissues, especially the spleen. Nasopharyngeal lymphoid hyperplasia was constant, in one instance suggesting tumor. Other tissues presented no significant gross features related to the primary disease except for (1) rather consistent enlargement of the liver, (2) infrequent icterus, and (3) occasional cutaneous rash. Histologic observations revealed more or less generalized lesions resembling those of certain known virus diseases, notably perivascular aggregates of normal and abnormal lymphocytes. Reaction of this type inconstantly involved all tissues studied except the bone marrow; here lymphocytes were virtually absent in sections, but were present in aspirated marrow because of dilution with peripheral blood.
More specific changes were invariably noted in lymphoid tissues. The abnormal lymphocyte characteristic of the disease could be identified in thin, lightly stained sections. Lymph node reactions varied from a predominantly follicular hyperplasia to a blurred pattern simulating a malignant lymphoma; the latter was due to a lymphocytic and reticulo-endothelial proliferation in the medullary cords. The spleen displayed a lymphocytic infiltration in the thinned capsule and trabeculae, frequently dissolving the latter and rendering the organ liable to rupture. The pattern was partially effaced in most instances and the follicles widely spaced. Blood sinuses contained considerable numbers of normal and abnormal lymphocytes, and accumulations of these cells constantly cuffed intratrabecular arteries and lay beneath the intima of veins. Tonsils displayed ulceration and necrosis in several cases, and the lymphocytic proliferation closely resembled malignant tumor in a tonsil that enlarged rapidly.
A pneumonic exudate in 1 case was almost exclusively of round cell type, while in another the pneumonia was of the usual lobular type with a neutrophilic exudate. Small myocardial infiltrates which we noted probably explain the electrocardiographic changes described in infectious mononucleosis. Other findings of particular interest were the periportal lymphoid collars in the liver which sometimes attained the proportions seen in leukemia, and the presence of meningo-encephalitis in 4 of the 6 brains examined.
We believe that the majority of cells in the lymphocytic "infiltrates" of connective tissues and the perivascular collars are metaplastic rather than inwandering, i.e., that they are formed in situ and stem from cells of the reticulo-endothelial system.
THE EFFECT OF FOLIC ACID ON THE TOXICITY OF ITS ANALOGUE 4-AMINOPTEROYLGLUTAMIC ACID (AMINOPTERIN)
Authors: HIGGINS GEORGE M. , STEMBER MURIEL , MONSEN HARRY 
Published: October 2019

Abstract
A study of some of the toxic reactions of 4-aminofolic acid together with the modifications of these reactions induced by giving varying amounts of folic acid daily to white rats is reported.
Seven groups of young male rats ranging in weight from 110 to 130 Gm. were arranged. Aminopterin (4-aminofolic acid) was given intraperitoneally, in amounts equivalent to 50 micrograms daily, to all rats of six of these seven groups. Folic acid was given by mouth to these animals in such amounts as to provide 5, 10, 20, 30 or 50 mg. daily to each animal respectively of five of the six groups receiving aminopterin. One group received the analogue without the vitamin. One group of 8 animals received neither the vitamin nor its analogue.
Observations continued for six days, when all surviving animals were killed and necropsy was performed. Data were assembled on the appetite, body weights, the weights of adrenals, thymus and spleen, the distribution of leukocytes in the peripheral blood and the changes in the bone marrow. The following conclusions seem warranted:
1. Aminopterin is extremely toxic and incites within six days anorexia, extreme diarrhea with atony of the entire gastro-intestinal tract, adrenal hyperplasia, atrophy of the thymus and spleen, and an inhibition to development of myeloid cells in the bone marrow.
2. Small amounts of folic acid are essentially without effect on the toxicity of that amount of the analogue we chose to administer.
3. Larger amounts of folic acid daily (30 mg.) proved effective in essentially inhibiting the development of the severe toxic reactions for the six-day period.
4. The severe toxicity of aminopterin does not manifest itself until the third or or fourth day of its daily administration. The onset of these symptoms is thereafter extremely rapid.
5. Thirty milligrams of folic acid daily will not indefinitely counteract the toxic symptoms induced by 50 micrograms of aminopterin. In our experience, within twelve to fourteen days, the characteristic syndrome will appear in spite of the continuous administration of the vitamin.
FETAL AND ADULT HEMOGLOBINS IN THE BLOOD OF INFANTS AFFECTED WITH HEMOLYTIC DISEASE OF THE NEWBORN
Authors: PONDER ERIC , LEVINE PHILIP 
Published: October 2019

Abstract
A method is described by means of which the rapidly denatured adult Hb can be separated from the slowly denatured fetal Hb by denaturing with alkali and precipitating the denatured material at its isoelectric point. When applied to 15 normal cord bloods and to the cord bloods of 15 infants affected with hemolytic disease of the newborn, the method showed no significant difference in the percentage of fetal Hb present.
Comparison of influenza A virus and formyl-methionyl-leucyl- phenylalanine activation of the human neutrophil
Authors: Hartshorn KL , Daigneault DE , White MR , Tuvin M , Tauber JL , Tauber AI 
Published: October 2019

Abstract
Influenza A virus (IAV) activates the human neutrophil, but induces a dysfunctional state as well. Cell activation may contribute to the containment of the virus and/or cause local tissue damage. Certain features of the neutrophil activation response elicited by IAV are distinctive when compared with that triggered by formyl-methyl-leucyl- phenylalanine (FMLP). An atypical respiratory burst response occurs in which hydrogen peroxide, but no superoxide, is formed. This unusual respiratory burst stoichiometry persists despite marked priming of the IAV-induced response. A comprehensive examination of the activation cascade initiated by these stimuli failed to show an explanation for these differences. Both IAV and FMLP comparably stimulate inositol trisphosphate and phosphatidic acid production. The subsequent increase in intracellular calcium (Ca2+i) upon FMLP stimulation was more dependent on extracellular Ca2+ than with IAV activation, but both stimuli induced Ca2+ influx. FMLP and IAV exhibited equal susceptibility to inhibition by protein kinase inhibitors in eliciting the respiratory burst, and actin polymerization occurred in response to each agonist. A possible explanation for the anomalous respiratory burst induced by IAV is that O2- is generated at an intracellular site inaccessible to assay, and/or virus binding to sialic acid constituents of the plasma membrane alters the O2- generating capacity of the respiratory burst oxidase; evidence for each mechanism is offered.
RARα1/RARα2-PML mRNA Expression in Acute Promyelocytic Leukemia Cells: A Molecular and Laboratory-Clinical Correlative Study
Authors: Li Yun-Ping , Andersen Janet , Zelent Arthur , Rao Sreenivas , Paietta Elisabeth , Tallman Martin S. , Wiernik Peter H. , Gallagher Robert E. 
Published: October 2019

Abstract
In addition to the major fusion gene PML-RARα, the t(15; 17) in acute promyelocytic leukemia (APL) produces the reciprocal fusion gene RARα-PML. To determine the scope of RARα-containing mRNA expression in APL cells, we tested PML-RARα–positive APL cells for the presence of mRNAs initiated from two distinct RARα gene promoters, α1 and α2. From the normal allele, both RARα1 and RARα2 mRNAs were expressed in all APL cases (N = 24). From the translocated allele, RARα1-PML mRNA was expressed in 77% and RARα2-PML mRNA in 28% of cases (N = 98). RARα2-PML mRNA was not observed in the absence of RARα1-PML mRNA. There was no association between RARα1-PML or RARα2-PML mRNA expression and the type of PML-RARα mRNA formed by either 5′ or 3′ breaksites in the PML gene. RARα1-PML mRNAs and RARα2-PML mRNAs from 5′ PML breaksite cases coded for full-length RARα-PML proteins but RARα2-PML mRNAs from 3′ PML breaksite cases encoded a truncated RARα2 peptide. RARα1/α2-PML mRNA expression was not associated with differences in APL cell sensitivity to all-trans retinoic acid(tRA)-induced differentiation in vitro or in clinical outcome after tRA or chemotherapy induction therapy (protocol E2491). Our analysis indicated that RARα1/α2-PML mRNA expression markedly differs from normal RARα1/α2 mRNA expression, that the difference in RARα1-PML and RARα2-PML mRNA expression frequency is primarily related to the genomic separation of the RARα1 and RARα2 coding exons, and that variations in RARα1/α2-PML mRNA expression likely have no clinically relevant function in APL cells.
TEL-JAK2 transgenic mice develop T-cell leukemia
Authors: Carron Clémence , Cormier Françoise , Janin Anne , Lacronique Virginie , Giovannini Marco , Daniel Marie-Thérèse , Bernard Olivier , Ghysdael Jacques 
Published: October 2019

Abstract
We previously reported a fusion between TEL and JAK2in a t(9;12)(p24;p13) chromosomal translocation in childhood acute T-cell leukemia. This fusion gene encodes a TEL-JAK2 chimeric protein in which the 336 amino-terminal residues of TEL, including its specific self-association domain, are fused to the kinase domain of JAK2. TEL-JAK2 exhibits constitutive activation of its tyrosine kinase activity which, in turn, confers growth factor–independent proliferation to the interleukin-3–dependent Ba/F3 hematopoietic cell line. To elucidate the properties of TEL-JAK2 in primary cells and to create an animal model for TEL-JAK2–induced leukemia, we generated transgenic mice in which the TEL-JAK2 complementary DNA was placed under the transcriptional control of the EμSR enhancer/promoter. TEL-JAK2 founder mice and their transgenic progeny developed fatal leukemia at 4 to 22 weeks of age. Selective amplification of CD8-positive T cells was observed in blood, lymph nodes, thymus, spleen, and bone marrow. Expression of a tyrosine-phosphorylated TEL-JAK2 protein and activation of STAT1 and STAT5 (signal transducer and activator of transcription) were detected in leukemic tissues. TEL-JAK2 diseased mice also displayed invasion of nonhematopoietic organs, including liver, brain, lung, and kidney, by leukemic T cells. Leukemic organs of founder and transgenic progeny contained a monoclonal/oligoclonal T-cell population as analyzed by the rearrangement of the TCRβ locus. Transplantation of TEL-JAK2 leukemic cells in nude mice confirmed their invasive nature. We conclude that the TEL-JAK2 fusion is an oncogene in vivo and that its expression in lymphoid cells results in the preferential expansion of CD8-positive T cells.
Megakaryocyte dense granule components are sorted in multivesicular bodies
Authors: Youssefian Tayebeh , Cramer Elisabeth M. 
Published: October 2019

Abstract
Recent studies suggest that multivesicular bodies are an intermediate stage in the formation of -granules. In contrast, the kinetics and mode of appearance of dense granules during megakaryocytic maturation has remained poorly understood. Immunoelectron microscopy was used to monitor the appearance of dense granular markers (granulophysin and serotonin) on cryosections of human megakaryocytes (MKs) cultured from CD34+ precursors. The monitoring was done on days 8 and 13 of culture. The data suggest that dense granules appear in immature MKs early during their maturation, concomitantly with -granule formation. In MKs of intermediary maturation stage, granulophysin was mainly localized within dense granules and multivesicular bodies (MVBs), which were also labeled for serotonin. This study provides evidence that granulophysin is a dense granule marker in human MKs and that MVBs are an intermediary stage of dense granule maturation and probably constitute a sorting compartment between -granules and dense granules.
A national atlas of tsetse and African animal trypanosomosis in Mali
Authors: Diarra Boucader , Diarra Modibo , Diall Oumar , Bass Boubacar , Sanogo Youssouf , Coulibaly Etienne , Sylla Mahamadou , Zhao Weining , Paone Massimo , Cecchi Giuliano 
Published: October 2019

AbstractBackgroundTsetse-transmitted trypanosomosis is a deadly, neglected tropical disease and a major challenge for mixed crop-livestock agriculture in sub-Saharan Africa. It is caused by several species of the genusTrypanosoma. Information on the occurrence of tsetse flies and African animal trypanosomosis (AAT) is available for different areas of Mali. However, these data have never been harmonized and centralized, which prevents the development of comprehensive epidemiological maps and constrains an evidence-based planning of control actions. To address this challenge, we created a dynamic geo-spatial database of tsetse and AAT distribution in Mali.MethodsA digital repository containing epidemiological data collected between 2000 and 2018 was assembled. In addition to scientific publications, the repository includes field datasheets, technical reports and other grey literature. The data were verified, harmonized, georeferenced and integrated into a single spatially-explicit database.ResultsFor the tsetse component, approximately 19,000 trapping records, corresponding to 6000 distinct trapping locations and 38,000 flies were included in the database.Glossina palpalis gambiensiswas the most widespread and abundant species, and it was found in the southern, southern-central and western parts of the country.Glossina tachinoideswas only found in the South. Only a few specimens ofGlossina morsitans submorsitanswere detected. For the AAT component, approximately 1000 survey records were included, corresponding to 450 distinct survey sites and 37,000 tested bovines. AAT was found in all surveyed regions, although data for the tsetse-free North and North-East are lacking.Trypanosoma vivaxandTrypanosoma congolensewere the dominant species, whileTrypanosoma bruceiinfections were much less numerous.ConclusionsThe atlas of tsetse and AAT in Mali provides a synoptic view of the vector and disease situation at the national level. Still, major geographical gaps affect the North, the North-East and the West, and there is also a severe lack of data over the past five years. Trypanosomosis remains a major animal health problem in Mali. However, despite its prevalence and distribution, monitoring and control activities are presently very limited. Efforts should be made to strengthen the progressive control of AAT in Mali, and the atlas provides a new tool to identify priority areas for intervention.
Quantitative proteomic analysis and functional characterization of Acanthamoeba castellanii exosome-like vesicles
Authors: Lin Wei-Chen , Tsai Chia-Yun , Huang Jian-Ming , Wu Shang-Rung , Chu Lichieh Julie , Huang Kuo-Yang 
Published: October 2019

AbstractBackgroundPathogenic protozoans use extracellular vesicles (EVs) for intercellular communication and host manipulation.Acanthamoeba castellaniiis a free-living protozoan that may cause severe keratitis and fatal granulomatous encephalitis. Although several secreted molecules have been shown to play crucial roles in the pathogenesis ofAcanthamoeba, the functions and components of parasite-derived EVs are far from understood.MethodsPurified EVs fromA. castellaniiwere confirmed by electron microscopy and nanoparticle tracking analysis. The functional roles of parasite-derived EVs in the cytotoxicity to and immune response of host cells were examined. The protein composition in EVs fromA. castellaniiwas identified and quantified by LC-MS/MS analysis.ResultsEVs fromA. castellaniifused with rat glioma C6 cells. The parasite-derived EVs induced an immune response from human THP-1 cells and a cytotoxic effect in C6 cells. Quantitative proteomic analysis identified a total of 130 proteins in EVs. Among the identified proteins, hydrolases (50.2%) and oxidoreductases (31.7%) were the largest protein families in EVs. Furthermore, aminopeptidase activities were confirmed in EVs fromA. castellanii.ConclusionsThe proteomic profiling and functional characterization of EVs fromA. castellaniiprovide an in-depth understanding of the molecules packaged into EVs and their potential mechanisms mediating the pathogenesis of this parasite.
Early outcomes of tapering jejunoplasty by antimesenteric seromuscular stripping and mucosal inversion for proximal jejunal atresia
Authors: Marei Mahmoud Marei , Abouelfadl Mohamed Hamed , Rawwash Ahmed Arafa Elsayed , Seleim Hamed Mahmoud , Mahmoud Wesam Mohamed , Yassin Tamer Yassin Mohamed , El-Tagy Gamal Hassan 
Published: October 2019

Abstract

Background
High jejunal atresia is associated with significant dilatation of the proximal segment. This poses two problems: (a) calibre discrepancy with the distal unused segment and (b) hypomotility causing stasis. Tapering jejunoplasty/enteroplasty could offer a practical solution in selected cases, leading to early establishment of feeds. This work aims to evaluate the outcome of tapering jejunoplasty including its effect on establishing enteral feeding in neonates with proximal jejunal atresia.

Results
Twenty-two neonates with jejunal atresia (types I, II and IIIa) were reviewed. Cases with multiple atresia, apple-peel variant and meconium ileus were excluded. The included cases fell retrospectively into two groups: group A (13 cases)—very proximal atresia and significant dilatation and group B (9 cases)—mid/distal jejunal atresia. For group A, we excised only the distal tip of the dilated bowel and stripped a seromuscular triangle up to the duodenojejunal flexure and inverted the mucosa along the antimesenteric border, followed by an end-to-oblique anastomosis. For group B, we performed a standard excision of a short proximal segment and an end-to-oblique anastomosis. There was no significant difference in the gestation age or birth weight between both groups. The mean operative time was 90 min for group A and 60 min for group B. The duration until full enteral feeds became tolerated, and parenteral nutrition was weaned accordingly was shorter in group A (mean 10.8 days) as compared to group B (mean 14.5 days), p = 0.045.

Conclusion
Tapering jejunoplasty by seromuscular stripping and mucosal inversion facilitates early establishment of feeds in proximal jejunal atresia.
Microtubules at focal adhesions – a double-edged sword
Authors: Seetharaman Shailaja , Etienne-Manneville Sandrine 
Published: October 2019

ABSTRACT
Cell adhesion to the extracellular matrix is essential for cellular processes, such as migration and invasion. In response to cues from the microenvironment, integrin-mediated adhesions alter cellular behaviour through cytoskeletal rearrangements. The tight association of the actin cytoskeleton with adhesive structures has been extensively studied, whereas the microtubule network in this context has gathered far less attention. In recent years, however, microtubules have emerged as key regulators of cell adhesion and migration through their participation in adhesion turnover and cellular signalling. In this Review, we focus on the interactions between microtubules and integrin-mediated adhesions, in particular, focal adhesions and podosomes. Starting with the association of microtubules with these adhesive structures, we describe the classical role of microtubules in vesicular trafficking, which is involved in the turnover of cell adhesions, before discussing how microtubules can also influence the actin–focal adhesion interplay through RhoGTPase signalling, thereby orchestrating a very crucial crosstalk between the cytoskeletal networks and adhesions.
Accuracy of multiparametric magnetic resonance imaging for detecting extracapsular extension in prostate cancer: a systematic review and meta-analysis
Authors: Zhang Fan , Liu Chen-Lu , Chen Qian , Shao Sheng-Chao , Chen Shuang-Qing 
Published: October 2019

Objective:
To evaluate the diagnostic accuracy of multiparametric MRI (mpMRI) for detecting extracapsular extension (ECE) in patients with prostate cancer (PCa).

Methods and materials:
We searched MEDLINE, PubMed, Embase and the Cochrane library up to December 2018. We included studies that used mpMRI to differentiate ECE from organ-confined PCa with a combination of T 2 weighted imaging (T 2WI), diffusion-weighted imaging, and dynamic contrast-enhanced MRI. All studies included had pathological diagnosis with radical prostatectomy. Two reviewers independently assessed the methodological quality of included studies by using Quality Assessment of Diagnostic Accuracy Studies 2 tool. We calculated pooled sensitivity, specificity, positive and negative predictive values, diagnostic odds ratios and receiver operating characteristic curve for mpMRI from 2 × 2 tables.

Results:
A total of 17 studies that comprised 3374 participants were included. The pooled data showed a sensitivity of 0.55 (95% confidence interval 0.43, 0.66]) and specificity of 0.87 (95% confidence interval 0.82, 0.91) for extracapsular extension detection in PCa.

Conclusion:
First, our meta-analysis shows moderate sensitivity and high specificity for mpMRI to differentiate ECE from organ-confined prostate cancer before surgery. Second, our meta-analysis shows that mpMRI had no significant differences in performance compared with the former meta-analysis with use of T 2WI alone or with additional functional MRI.

Advances in knowledge:
It is the first meta-analysis to evaluate the accuracy of mpMRI in combination of TWI, diffusion-weightedimaging and dynamiccontrast-enhanced-MRI for extracapsular extension detection.