• Tuberculosis and Respiratory Diseases
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• v.40 no.1
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• pp.16-22
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• 1993

Background: The Microbicidal and cytotoxic activities of neutrophils are to a large extent dependent on a burst of oxidative metabolism which generates superoxide anion, hydrogen peroxide, and other reactive products of oxygen. The respiratory burst of PMN is initiated by intracellular calcium mobilization that follows immune or particular stimulation and is very sensitive to modulation by c-AMP or adenosine. Despite its antagonism against adenosine, earlier study has demonstrated potent theophylline inhibition of the PMN respiratory burst at variable ranges of blood concentrations of theophylline in the healthy normal volunteers and in the septic animals pretreated or early post-treated with aminophylline (AMPH) or pentoxifylline. However it is unclear whether theophylline inhibits the superoxide generation or not in the established human sepsis caused by acute pneumonia, as taking into consideration of the fact that full activation of neutrophils have occurred within minutes after the septic insult in the animal experiments. Methods: We measured the $O_2$ generation of peripheral arterial neutrophils obtained from 11 human septic subjects caused by acute pneumonia before and 1 hour after completion of continuous AMPH infusion. Patients were identified and studied within 48 hour of admission. All subjects were administered an intravenous loading and maintenance dose of AMPH. The generation of $O_2$ was measured at a discrete time point (60 min) by the reduction of ferricytochrome c.PMA (10 ${\mu}g/ml$) was used as a stimulating agent. PMNs were isolated at a concentration of $2{\times}10^6$ cells/ml. The arterial oxygen tension, blood pressure and heart rates were also checked to evaluate the systemic effects of AMPH in the acute pneumonia. Results: The mean serum concentration of AMPH at 60 minutes was $8.8{\pm}0.6{\mu}g/ml$. Sixty minutes after AMPH infusion the generatition of $O_2$ was decreased from $0.076{\pm}0.034$ to $0.013{\pm}0.004$(OD) (p<0.05) and from $0.177{\pm}0.044$ to $0.095{\pm}0.042$(OD) (p<0.01) in the resting and stimulated PMNs respectively. $PaO_2$ was not changed after AMPH infusion. Conclusion: AMPH may compromise host defense by significant inhibition of neutrophil release of superoxide anion and it had no effect on improving $PaO_2$ in the acute pneumonia.

• Journal of Life Science
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• v.31 no.10
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• pp.913-921
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• 2021

Limb-girdle muscular dystrophy (LGMD) which is characterized by progressive muscle weakening of the hip and shoulder shows both dominant and recessive inheritances with many pathogenic genes including TTN. This study performed to identify genetic causes of a male patient with late onset (45 years old) autosomal recessive LGMD and atrial flutter. By application of the whole exome sequencing, we identified bi-allelic variants of TTN gene in the patient. One allele had a single missense variant of [c.24124G>T (p.V8042F)], while the other allele consisted of three missense variants of [c.29222G>C (p.R9741P) + c.67490A>G (p.H22497R) + c.75376C>T (p.R25126C)]. The p.V8042F allele was transmitted from his mother, while the other haplotype allele was putatively transmitted from his father. His two unaffected sons had only the p.R9741P. These variants have been not reported or rarely reported in the public human genome databases (1,000 Genome, gnomAD, and KRGDB). Most variants were located in the highly conserved immunoglobulin or fibronectin domains and were predicted to be pathogenic by the in silico analyses. The TTN giant protein plays a key role in muscle assembly, force transmission at the Z-line, and maintenance of resting tension in the I-band. In conclusion, we think that these bi-allelic compound heterozygous mutations may play a role as the genetic causes of the LGMD phenotype.