scholarly journals Which Therapy for Non-Type(T)2/T2-Low Asthma

2021 ◽  
Vol 12 (1) ◽  
pp. 10
Author(s):  
Fabio L. M. Ricciardolo ◽  
Vitina Carriero ◽  
Francesca Bertolini
Keyword(s):  
Molecular Mechanisms ◽  
Inhaled Corticosteroids ◽  
First Choice ◽  
Inflammatory Processes ◽  
Muscarinic Drugs ◽  
Long Acting ◽  
Type 3

Currently, the asthmatic population is divided into Type 2-high and non-Type 2/Type 2-low asthmatics, with 50% of patients belonging to one of the two groups. Differently from T2-high, T2-low asthma has not been clearly defined yet, and the T2-low patients are identified on the basis of the absence or non-predominant expression of T2-high biomarkers. The information about the molecular mechanisms underpinning T2-low asthma is scarce, but researchers have recognized as T2-low endotypes type 1 and type 3 immune response, and remodeling events occurring without inflammatory processes. In addition, the lack of agreed biomarkers reprents a challenge for the research of an effective therapy. The first-choice medication is represented by inhaled corticosteroids despite a low efficacy is reported for/in T2-low patients. However, macrolides and long-acting anti-muscarinic drugs have been recognized as efficacious. In recent years, clinical trials targeting biomarkers playing key roles in T3 and T1 immune pathways, alarmins, and molecules involved in neutrophil recruitment have provided conflicting results probably misleading (or biased) in patients’ selection. However, further studies are warranted to achieve a precise characterization of T2-low asthma with the aim of defining a tailored therapy for each single asthmatic patient.

scholarly journals Characterization of cDNAs encoding isoforms of hamster 3 beta-hydroxysteroid dehydrogenase/delta 5-->4 isomerase

1998 ◽  
Vol 20 (1) ◽  
pp. 99-110 ◽  
Author(s):  
FM Rogerson ◽  
J Courtemanche ◽  
A Fleury ◽  
JG LeHoux ◽  
JI Mason ◽  
...  
Keyword(s):  
Hydroxysteroid Dehydrogenase ◽  
Cdna Libraries ◽  
Sexually Dimorphic ◽  
High Affinity ◽  
Liver And Kidney ◽  
Low Levels ◽  
Type 3

Western blot analyses of various hamster tissues reveal high levels of expression of 3 beta-hydroxysteroid dehydrogenase (3 beta-HSD) in adrenal and liver, and moderate levels of expression in kidney. The expression in liver is sexually dimorphic; very high levels of protein are observed in adult male liver but very low levels are seen in the female liver. Three distinct cDNAs encoding isoforms of 3 beta-HSD were isolated from hamster cDNA libraries. The type 1 isoform is a high-affinity dehydrogenase/isomerase expressed in adrenal and male kidney. The type 2 isoform is also a high-affinity dehydrogenase/isomerase expressed in kidney and male liver. The type 3 enzyme is a 3-ketosteroid reductase expressed predominantly in kidney. Sequencing of the clones showed that all three are structurally very similar, although types 1 and 2 share the greatest degree of similarity. Immunohistochemical staining for 3 beta-HSD in the adrenal was found throughout the adrenal cortex. In the kidney staining was confined to tubules, and in the liver, heavy staining was found in hepatocytes. The cloning of cDNAs for 3 beta-HSD from the liver and kidney should help in elucidating the function of this enzyme in these tissues.

Altered expression of major renal Na transporters in rats with unilateral ureteral obstruction

2003 ◽  
Vol 284 (1) ◽  
pp. F155-F166 ◽  
Author(s):  
Chunling Li ◽  
Weidong Wang ◽  
Tae-Hwan Kwon ◽  
Mark A. Knepper ◽  
Søren Nielsen ◽  
...  
Keyword(s):  
Ureteral Obstruction ◽  
Molecular Mechanisms ◽  
Free Water ◽  
Fractional Excretion ◽  
Unilateral Ureteral Obstruction ◽  
Altered Expression ◽  
Compensatory Increase ◽  
Type 3

It has been demonstrated previously that ureteral obstruction was associated with downregulation of renal AQP2 expression and an impaired urinary concentrating capacity (Li C, Wang W, Kwon TH, Isikay L, Wen JG, Marples D, Djurhuus JC, Stockwell A, Knepper MA, Nielsen S, and Frøkiær J. Am J Physiol Renal Physiol 281: F163–F171, 2001). In the present study, changes in the expression of major renal Na transporters were examined in a rat model with 24 h of unilateral ureteral obstruction (UUO) to clarify the molecular mechanisms of the marked natriuresis seen after release of UUO. Urine collection for 2 h after release of UUO revealed a significant reduction in urinary osmolality, solute-free water reabsorption, and a marked natriuresis (0.29 ± 0.03 vs. 0.17 ± 0.03 μmol/min, P < 0.05). Consistent with this, immunoblotting revealed significant reductions in the abundance of major renal Na transporters: type 3 Na+/H+exchanger (NHE3; 24 ± 4% of sham-operated control levels), type 2 Na-Pi cotransporter (NaPi-2; 21 ± 4%), Na-K-ATPase (37 ± 4%), type 1 bumetanide-sensitive Na-K-2Cl cotransporter (BSC-1; 15 ± 3%), and thiazide-sensitive Na-Cl cotransporter (TSC; 15 ± 4%). Immunocytochemistry confirmed the downregulation of NHE3, BSC-1, and TSC in response to obstruction. In nonobstructed contralateral kidneys, a significant reduction in the abundance of inner medullary Na-K-ATPase and cortical NaPi-2 was found. This may contribute to the compensatory increase in urinary production (23 ± 2 vs. 13 ± 1 μl · min−1 · kg−1) and increased fractional excretion of urinary Na (0.62 ± 0.03 vs. 0.44 ± 0.03%, P < 0.05). In conclusion, downregulation of major renal Na transporters in rats with UUO may contribute to the impairment in urinary concentrating capacity and natriuresis after release of obstruction, and reduced levels of Na-K-ATPase and NaPi-2 in the contralateral nonobstructed kidney may contribute to the compensatory increase in water and Na excretion from that kidney during UUO and after release of obstruction.

scholarly journals Novel LinA Type 3 δ-Hexachlorocyclohexane Dehydrochlorinase

2015 ◽  
Vol 81 (21) ◽  
pp. 7553-7559 ◽  
Author(s):  
Nidhi Shrivastava ◽  
Zbynek Prokop ◽  
Ashwani Kumar
Keyword(s):  
Amino Acid ◽  
Primary Structure ◽  
Degradation Pathway ◽  
Amino Acid Residues ◽  
Hch Isomers ◽  
New Variant ◽  
Type 3

ABSTRACTLinA is the first enzyme of the microbial degradation pathway of a chlorinated insecticide, hexachlorocyclohexane (HCH), and mediates the dehydrochlorination of α-, γ-, and δ-HCH. Its two variants, LinA type 1 and LinA type 2, which differ at 10 out of 156 amino acid residues, have been described. Their activities for the metabolism of different HCH isomers differ considerably but overall are high for γ-HCH, moderate for α-HCH, low for δ-HCH, and lacking for β-HCH. Here, we describe the characterization of a new variant of this enzyme, LinA type 3, whose gene was identified from the metagenome of an HCH-contaminated soil sample. Its deduced primary structure in the region spanning amino acid residues 1 to 147 of the protein exhibits 17 and 12 differences from LinA type 1 and LinA type 2, respectively. In addition, the residues GIHFAPS, present at the region spanning residues 148 to 154 in both LinA type 1 and LinA type 2, are deleted in LinA type 3.The activity of LinA type 3 for the metabolism of δ-HCH is several orders of magnitude higher than that of LinA type 1 or LinA type 2 and can be useful for improvement of the metabolism of δ-HCH.

Altered expression of major renal Na transporters in rats with bilateral ureteral obstruction and release of obstruction

2003 ◽  
Vol 285 (5) ◽  
pp. F889-F901 ◽  
Author(s):  
Chunling Li ◽  
Weidong Wang ◽  
Tae-Hwan Kwon ◽  
Mark A. Knepper ◽  
Søren Nielsen ◽  
...  
Keyword(s):  
Ureteral Obstruction ◽  
Molecular Mechanisms ◽  
Urinary Tract Obstruction ◽  
Urinary Sodium Excretion ◽  
Urinary Sodium ◽  
Altered Expression ◽  
Sodium Transporters ◽  
Type 3

Urinary tract obstruction impairs urinary concentrating capacity and reabsorption of sodium. To clarify the molecular mechanisms of these defects, expression levels of renal sodium transporters were examined in rats with 24-h bilateral ureteral obstruction (BUO) or at day 3 or 14 after release of BUO (BUO-R). BUO resulted in downregulation of type 3 Na+/H+ exchanger (NHE3) to 41 ± 14%, type 2 Na-Pi cotransporter (NaPi-2) to 26 ± 6%, Na-K-ATPase to 67 ± 8%, type 1 bumetanide-sensitive Na-K-2Cl cotransporter (BSC-1) to 20 ± 7%, and thiazide-sensitive cotransporter (TSC) to 37 ± 9%. Immunocytochemistry confirmed downregulation of NHE3, NaPi-2, Na-K-ATPase, BSC-1, and TSC. Consistent with this downregulation, BUO-R was associated with polyuria, reduced urinary osmolality, and increased urinary sodium and phosphate excretion. BUO-R for 3 days caused a persistant downregulation of NHE3 to 53 ± 10%, NaPi-2 to 57 ± 9%, Na-K-ATPase to 62 ± 8%, BSC-1 to 50 ± 12%, and TSC to 56 ± 16%, which was associated with a marked reduction in the net renal reabsorption of sodium (616 ± 54 vs. 944 ± 24 μmol · min-1 · kg-1; P < 0.05) and phosphate (6.3 ± 0.9 vs. 13.1 ± 0.4 μmol · min-1 · kg-1; P < 0.05) demonstrating a defect in renal sodium and phosphate reabsorption capacity. Moreover, downregulation of Na-K-ATPase and TSC persisted in BUO-R for 14 days, whereas NHE3, NaPi-2, and BSC-1 were normalized to control levels. In conclusion, downregulation of renal Na transporters in rats with BUO and release of BUO are likely to contribute to the associated urinary concentrating defect, increased urinary sodium excretion, and postobstructive polyuria.

scholarly journals Identification and Partial Characterization of Endogenous Double-stranded Ribonucleic Acid in Mulberry

1994 ◽  
Vol 119 (4) ◽  
pp. 859-861
Author(s):  
S.T. Nameth ◽  
S.L. Cheng
Keyword(s):  
Ribonucleic Acid ◽  
Rnase A ◽  
Deciduous Tree ◽  
Virus Particles ◽  
Molecular Weights ◽  
Low Salt ◽  
Type 3

Double-stranded ribonucleic acid (dsRNA) analysis of apparently healthy red mulberry (Morus rubra L.) yielded four distinct dsRNA banding profiles. dsRNA type 1 contained three dsRNA bands with approximate molecular weights (MWs) of 12.0, 1.0, and 0.9 × 106, respectively. dsRNA type 2 contained two dsRNA bands with MWs of 1.0 and 0.9 × 106. dsRNA type 3 contained four dsRNA bands with MWs of 1.0, 0.9, 0.89, and 0.88 × 106. dsRNA type 4 contained three dsRNA bands with MWs of 1.0, 0.88, and 0.87 × 106. No virus particles were associated with any of the samples analyzed. All four types of dsRNA were resistant to DNase I and RNase A in high salt and susceptible to RNase A in low salt. Mulberry dsRNAs were somewhat similar to endogenous dsRNAs (edsRNA) associated with other hosts. This is the first report of edsRNA associated with a deciduous tree.

Characterization of mycoplasmas isolated from the great apes

1970 ◽  
Vol 16 (12) ◽  
pp. 1331-1339 ◽  
Author(s):  
Barry C. Cole ◽  
John R. Ward ◽  
Laura Golightly-Rowland ◽  
Charles E. Graham
Keyword(s):  
Adult Female ◽  
Great Apes ◽  
Young Female ◽  
Primate Species ◽  
Mycoplasma Species ◽  
Type 3

Nine adult female chimpanzees, five adult female orangutans, and three young female gorillas were cultured for mycoplasmas. All animals were found to harbor at least one species of mycoplasma and some as many as four. On the basis of physiological and serological characteristics mycoplasmas closely related or identical with M. hominis, M. salivarium, and M. orale types 1 and 2 were identified. The M. hominis strains which were restricted to the chimpanzee comprised two serologic subgroups but were physiologically homogeneous. The M. salivarium strains were physiologically and morphologically heterogeneous, with both lipolytic and non-lipolytic strains being isolated from the salivas of all three primate species. All strains of M. salivarium were closely related serologically. In addition to the above species, three unidentifiable types were encountered. Type 1 strains were isolated from the vaginas of two chimpanzees. The type 2 strain, which shared up to three antigenic components with various human mycoplasmas, was isolated from the oropharynx of a chimpanzee. The type 3 strains constituted the only mycoplasma species isolated from the orangutan vagina.

scholarly journals Genital warts in Burmeister's porpoises: characterization of Phocoena spinipinnis papillomavirus type 1 (PsPV-1) and evidence for a second, distantly related PsPV

2007 ◽  
Vol 88 (7) ◽  
pp. 1928-1933 ◽  
Author(s):  
Marie-Françoise Van Bressem ◽  
Patricia Cassonnet ◽  
Annabel Rector ◽  
Christian Desaintes ◽  
Koen Van Waerebeek ◽  
...  
Keyword(s):  
Phylogenetic Trees ◽  
Genital Warts ◽  
Bovine Papillomavirus ◽  
Reading Frame ◽  
Bona Fide ◽  
Type 3

We identified sequences from two distantly related papillomaviruses in genital warts from two Burmeister's porpoises, including a PV antigen-positive specimen, and characterized Phocoena spinipinnis papillomavirus type 1 (PsPV-1). The PsPV-1 genome comprises 7879 nt and presents unusual features. It lacks an E7, an E8 and a bona fide E5 open reading frame (ORF) and has a large E6 ORF. PsPV-1 L1 ORF showed the highest percentage of nucleotide identity (54–55 %) with human papillomavirus type 5, bovine papillomavirus type 3 (BPV-3) and Tursiops truncatus papillomavirus type 2 (TtPV-2). This warrants the classification of PsPV-1 as the prototype of the genus Omikronpapillomavirus. PsPV-1 clustered with TtPV-2 in the E6 and E1E2 phylogenetic trees and with TtPV-2 and BPV-3 in the L2L1 tree. This supports the hypothesis that PV evolution may not be monophyletic across all genes.

Novel Clinical Manifestation of the Known SCN5A D1790G Mutation

Cardiology ◽  
2015 ◽  
Vol 132 (4) ◽  
pp. 228-232 ◽  
Author(s):  
Miry Blich ◽  
Edna Efrati ◽  
Ibrahim Marai ◽  
Mahmoud Suleiman ◽  
Lior Gepstein ◽  
...  
Keyword(s):  
Sodium Channel ◽  
Molecular Mechanisms ◽  
Long Qt ◽  
Gene Encoding ◽  
Inactivation Curve ◽  
Channel Expression ◽  
Steady State Inactivation ◽  
Type 3

The D1790G mutation was found in all 24 patients of an extended long QT family but not in 200 chromosomes carried by healthy individuals. We describe a 37-year-old man presenting with a typical spontaneous type 1 Brugada pattern who in electrophysiological testing had easily inducible ventricular fibrillation. At the age of 47 years he had an atrial ventricular type 2 block documented by an exercise test and a Holter monitor. Genetic analysis revealed a known D1790G mutation in the gene encoding of the sodium channel (SCN5A) that until now has been associated only with the long QT phenotype. Although this mutation has not been associated with a reduction of sodium channel expression, we hypothesize that sodium currents are further diminished due to the 20-mV shift of the steady-state inactivation curve, and this could contribute to the Brugada phenotype. This case is important as it allows a better understanding of the underlying molecular mechanisms of Brugada syndrome. Moreover, this observation raises concern about the safety of class IC drug therapy in long QT type 3 patients and quinidine therapy in Brugada patients, and emphasizes the importance of a thorough clinical and genetic evaluation.

FUNCTIONAL STATUS AND ADAPTIVE POTENTIAL IN FOREIGN STUDENTS WITH DIFFERENT TYPES OF VEGETATIVE REGULATION DURING TUITION

2020 ◽  
pp. 118-126
Author(s):  
A.M. Satarkulova
Keyword(s):  
Heart Rate ◽  
Foreign Students ◽  
Autonomic Regulation ◽  
The Body ◽  
Functional Changes ◽  
Different Types ◽  
Type 3 ◽  
Adaptive Abilities

The assessment and dynamic control over students’ status is a very important task. It allows timely detection of prenosological status prior to pathology and health maintenance in students. The objective of the paper is to assess the adaptive abilities of the body, to analyze changes in heart rate variability indicators in students with various types of autonomic regulation, to identify prenosological status and precursory pathological symptoms. Materials and Methods. The study enrolled 302 students from India, aged 21.54±1.43. Programming complex «Psychophysiologist» was used to register the main HRV parameters within 5 minutes. Health status was evaluated according to the index of functional changes and the scale of functional states. Results. N.I. Shlyk (2009) distinguished two groups of students with different types of autonomic regulation: type 1 (53 %) with moderate and type 2 (5 %) with marked characteristics of central regulation profile, type 3 (35 %) with moderate and type 4 (7 %) with marked characteristics of autonomous regulation profile. Main parameters of HRV and adaptation potential were defined for each student.All the parameters characterized functional and health status. Conclusions. It was shown that 82 % of trial subjects (type 1), 53 % (type 2), 94 % (type 3) and 95 % (type 4) demonstrated satisfactory adaptation and their physiological processes were at an optimal level. 18 % of students (type 1) demonstrated reduced adaptive abilities of the body. Moreover, they were under moderate stress. 47 % of subjects (type 2) were also under a significant stress, which was proven by excessively high SI, low SDNN and TP, and an increased index of functional changes. 5 % of students (type 4) revealed dysfunctional characteristics in the heart rhythm, peculiar to pathology. Keywords: foreign students, heart rate variability, types of autonomic regulation, adaptation potential, functional status. Оценка состояния студентов и динамический контроль за ним является важной задачей, поскольку позволяет своевременно выявлять у студентов донозологические состояния, предшествующие патологии, и способствовать сохранению здоровья. Цель. Оценка адаптивных возможностей организма, анализ изменений показателей вариабельности сердечного ритма у студентов с различными типами вегетативной регуляции, выявление донозологических состояний и ранних признаков патологии. Материалы и методы. В исследовании участвовало 302 студента в возрасте 21,54+1,43 года из Индии. Регистрировались основные параметры ВСР в течение 5 мин с использованием программно-аппаратного комплекса «Психофизиолог». Состояние и уровень здоровья оценивались по индексу функциональных изменений и шкале функциональных состояний. Результаты. По способу, предложенному Н.И. Шлык, выделены группы студентов с различными типами вегетативной регуляции: I (53 %) и II типы (5 %) – с умеренным и выраженным преобладанием центрального контура регуляции соответственно, III (35 %) и IV типы (7 %) – с умеренным и выраженным преобладанием автономного контура регуляции соответственно. У каждого из студентов определены основные параметры ВСР и адаптационного потенциала, характеризующие функциональное состояние и уровень здоровья. Выводы. Показано, что для 82 % обследуемых с I типом, 53 % со II типом, 94 % c III типом и 95 % с IV типом регуляции характерно состояние удовлетворительной адаптации, физиологические процессы сохраняются на оптимальном уровне. В группе студентов I типа у 18 % студентов адаптивные возможности организма снижены, выявлено состояние умеренного напряжения. У 47 % обследуемых II типа также зафиксировано состояние резко выраженного напряжения, индикатором которого является чрезмерно высокое значение SI, низкие величины SDNN и ТP, повышенное значение индекса функциональных изменений. В группе студентов с IV типом у 5 % учащихсяв регуляции ритма сердца выявлены дисфункциональные признаки, характерные для патологии. Ключевые слова: иностранные студенты, вариабельность сердечного ритма, типы вегетативной регуляции, адаптационный потенциал, функциональное состояние.

POLIOMYELITIS IN CANADIAN ESKIMOS: LABORATORY STUDIES. V. TYPE 1 AND TYPE 3 POLIOMYELITIS ANTIBODY LEVELS IN BAFFIN ISLAND ESKIMOS

1954 ◽  
Vol 32 (1) ◽  
pp. 119-125
Author(s):  
W. Wood ◽  
Eina M. Clark ◽  
F. T. Shimada ◽  
A. J. Rhodes
Keyword(s):  
Medical Records ◽  
Baffin Island ◽  
Tissue Cultures ◽  
Laboratory Studies ◽  
Poliomyelitis Virus ◽  
Antibody Titers ◽  
Antibody Levels ◽  
Type 3

Studies on the basic immunology of poliomyelitis in Canadian Eskimos have been continued. Some 87 sera collected from Eskimos at Pangnirtung, Baffin Island, have been examined for the presence of Type 1 and Type 3 poliomyelitis antibody by quantitative tests in tissue cultures. The same sera were previously examined for Type 2 antibody by quantitative tests in mice. The results of the three determinations are now presented together for comparison. These sera came from Eskimos aged 2 to 72 years of age. None of the Eskimos showed any evidence of paralysis. Examination of the medical records did not suggest that any paralytic disease had been present in this part of Baffin Island. Very few of the sera showed the presence of poliomyelitis antibody; thus, Type 1 antibody was demonstrated in the sera of 8%, Type 2 antibody in the sera of 9%, and Type 3 antibody in the sera of 14%. No significant number of Eskimos below the age of 45 years had acquired poliomyelitis antibody. The antibody titers mostly ranged between 10−1.0 and 10−2.0, and were significantly lower than the titers customarily found in recently paralyzed cases. These findings suggest that poliomyelitis infection occurred in Pangnirtung Eskimos many years before the date on which the samples were taken (1951). These results point to the worldwide prevalence of the three types of poliomyelitis virus.

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