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1.  Genetic susceptibility to COPD 
Thorax  2000;55(8):722.
doi:10.1136/thorax.55.8.722b
PMCID: PMC1745824  PMID: 10950722
2.  Transcranial magnetic stimulation in ALS 
Neurology  2009;72(6):498-504.
Objective:
To investigate transcranial magnetic stimulation (TMS) measures as clinical correlates and longitudinal markers of amyotrophic lateral sclerosis (ALS).
Methods:
We prospectively studied 60 patients with ALS subtypes (sporadic ALS, familial ALS, progressive muscular atrophy, and primary lateral sclerosis) using single pulse TMS, recording from abductor digiti minimi (ADM) and tibialis anterior (TA) muscles. We evaluated three measures: 1) TMS motor response threshold to the ADM, 2) central motor conduction time (CMCT), and 3) motor evoked potential amplitude (correcting for peripheral changes). Patients were evaluated at baseline, compared with controls, and followed every 3 months for up to six visits. Changes were analyzed using generalized estimation equations to test linear trends with time.
Results:
TMS threshold, CMCT, and TMS amplitude correlated (p < 0.05) with clinical upper motor neuron (UMN) signs at baseline and were different (p < 0.05) from normal controls in at least one response. Seventy-eight percent of patients with UMN (41/52) and 50% (4/8) of patients without clinical UMN signs had prolonged CMCT. All three measures revealed significant deterioration over time: TMS amplitude showed the greatest change, decreasing 8% per month; threshold increased 1.8% per month; and CMCT increased by 0.9% per month.
Conclusions:
Transcranial magnetic stimulation (TMS) findings, particularly TMS amplitude, can objectively discriminate corticospinal tract involvement in amyotrophic lateral sclerosis (ALS) from controls and assess the progression of ALS. While central motor conduction time and response threshold worsen by less than 2% per month, TMS amplitude decrease averages 8% per month, and may be a useful objective marker of disease progression.
GLOSSARY
= abductor digiti minimi;
= amyotrophic lateral sclerosis;
= analysis of variance;
= confidence interval;
= compound motor action potential;
= central motor conduction time;
= deep tendon stretch reflex;
= familial ALS;
= generalized estimation equations;
= lower motor neuron;
= motor evoked potential;
= primary lateral sclerosis;
= progressive muscular atrophy;
= sporadic ALS;
= tibialis anterior;
= transcranial magnetic stimulation;
= upper motor neuron.
doi:10.1212/01.wnl.0000341933.97883.a4
PMCID: PMC2677511  PMID: 19204259
3.  Intermuscular adipose tissue rivals visceral adipose tissue in independent associations with cardiovascular risk 
Background
The metabolic implications of intermuscular adipose tissue (IMAT) are poorly understood compared to those of visceral adipose tissue (VAT) even though the absolute quantities of both depots are similar in many individuals.
Objective
The aim was to determine the independent relationship between whole-body IMAT and cardiovascular risk factor parameters.
Design
Whole body magnetic resonance imaging (MRI) was used to quantify total skeletal muscle (SM), total adipose tissue (TAT) of which IMAT, defined as the AT visible by MRI within the boundary of the muscle fascia, is a sub-component. Fasting serum measures (n = 262) of glucose, total cholesterol (T-Chol), high-density lipoprotein cholesterol (HDL-Chol), triglycerides (TG), protein bound glucose (PBG, n = 206) and insulin (n = 119) were acquired in healthy African-American (AA, n = 78) and Caucasian (Ca, n = 109) women (body mass index (BMI) 26.5±5.7 kg/m2; 44.4±16.4 years) and men (39 AA, 62 Ca; BMI 25.6±3.5 kg/m2; 45.6±17.4 years). General linear models identified the independent effects of IMAT after covarying for SM, VAT, TAT, race, sex and two-way interactions.
Results
Significant independent associations were observed for IMAT with glucose (P < 0.001), PBG (P < 0.001) and T-Chol (P < 0.05). The association of IMAT with cholesterol differed by race in such a manner that for a unit increase in IMAT, T-Chol increased more rapidly in Ca compared to AA (P < 0.05). TG, HDL-Chol and insulin had no independent association with IMAT.
Conclusion
The strong independent associations of IMAT with fasting glucose and PBG suggest that IMAT may be related to glucose metabolism; however, IMAT is also associated with T-Chol in Ca.
doi:10.1038/sj.ijo.0803621
PMCID: PMC2752367  PMID: 17452994
muscle fat; adipose tissue; imaging; body composition; health risk
4.  Genetic susceptibility to chronic obstructive pulmonary disease in Koreans: combined analysis of polymorphic genotypes for microsomal epoxide hydrolase and glutathione S-transferase M1 and T1 
Thorax  2000;55(2):121-125.
BACKGROUND—Although smoking is the major causal factor in the development of chronic obstructive pulmonary disease (COPD), only 10-20% of chronic heavy cigarette smokers develop symptomatic COPD which suggests the presence of genetic susceptibility. This genetic susceptibility to COPD might depend on variations in enzyme activities that detoxify cigarette smoke products such as microsomal epoxide hydrolase (mEPHX) and glutathione-S transferase (GST). As there is increasing evidence that several genes influence the development of COPD, multiple gene polymorphisms should be investigated to find out the genetic susceptibility to COPD.
METHODS—The genotypes of 83 patients with COPD and 76 healthy smoking control subjects were determined by polymerase chain reaction (PCR) followed by restriction fragment length polymorphism (PCR-RFLP) for the mEPHX gene, and multiplex PCR for GST M1 and GST T1 genes. The frequencies of polymorphic genotypes of mEPHX, GST M1, and GST T1 genes were compared both individually and in combination in patients with COPD and healthy smokers.
RESULTS—No differences were observed in the frequency of polymorphic genotypes in exons 3 and 4 of mEPHX, GST M1, and GST T1 genes between patients with COPD and healthy smokers. The frequencies of any combination of these genotypes also showed no differences between the COPD group and the control group.
CONCLUSIONS—Genetic polymorphisms in mEPHX, GST M1, and GST T1 genes are not associated with the development of COPD in Koreans.


doi:10.1136/thorax.55.2.121
PMCID: PMC1745681  PMID: 10639528
5.  The binding of two dimers of IciA protein to the dnaA promoter 1P element enhances the binding of RNA polymerase to the dnaA promoter 1P. 
Nucleic Acids Research  1997;25(17):3486-3489.
Transcription of the dnaA gene from the promoter 1P has been shown to be activated in vitro and in vivo by the binding of IciA protein to two sites on the dnaA promoter region [Lee, Y. S., Kim, H., and Hwang, D. S. (1996) Mol. Microbiol . 19, 389-396; Lee, Y. S., and Hwang, D. S. (1997) J. Biol. Chem. 272, 83-88]. In vitro transcription assays using DNA fragments carrying variable combinations of two IciA binding sites revealed that IciA binding site I (IciA I site), which is located upstream of the promoter 1P, is responsible for the transcriptional activation. Binding of one dimeric IciA protein to the IciA I site is followed by binding of the second dimer. Two dimers of IciA protein, rather than one dimer, on the IciA I site appeared to enhance the binding of RNA polymerase to the promoter 1P, resulting in the activation of transcription from the promoter 1P.
PMCID: PMC146913  PMID: 9254708
6.  Gene expression and cytopathic effect of vaccinia virus inactivated by psoralen and long-wave UV light. 
Journal of Virology  1996;70(1):165-171.
Induction of the cytopathic effect (CPE) in cells infected with poxvirus seems ubiquitous in that it has been associated with all different strains and preparations of poxviruses, regardless of the replicating status of these viruses. The study of the mechanisms by which CPE is induced by nonreplicating poxviruses is hampered by the lack of any noncytopathic mutant strains and preparations. In this paper, we report on the patterns of gene expression and induction of CPE by vaccinia viruses treated by limited cross-linking with psoralen and long-wave UV light (PLWUV). We show that treatment of cell-free virus with PLWUV could inactivate viral replication without abolishing the ability of the virus to infect cells. Viral transcription as indicated by reporter genes was generally enhanced and prolonged under early viral promoters and abolished under late promoters. Furthermore, increasing the levels of cross-linking with PLWUV resulted in a decrease and abolishment of viral expression of a large reporter gene and a concomitant loss of the induction of CPE. Cells infected with such a virus were able to express the reporter genes and proliferate. The generation of nonreplicating and noncytopathic recombinant vaccinia viruses may help in studies of the mechanisms of CPE induction by poxvirus and may facilitate the use of poxviral vectors in broader areas of research and clinical applications.
PMCID: PMC189801  PMID: 8523521
7.  Sequential changes of traumatic vertebral compression fracture on MR imaging. 
Journal of Korean Medical Science  1995;10(3):189-194.
The purpose of this study was to evaluate the sequential signal intensity changes in post-traumatic vertebral compression fractures of varying ages. Sixty-six patients with 115 post-traumatic vertebral compression fractures underwent MR imaging. The ages of fractures at the time of MR images ranged from 1 day to 6 years. Sequential follow-up MR imagings were obtained in 4 patients for 2 years after initial MR examination. The fracture sites in all 52 fractures with traumatic events less than 3 months prior were hypointense on T1-weighted images and hyperintense on T2-weighted images (type I). A type I fracture could be subdivided into 3 patterns depending on its morphologic appearance: diffuse (type Ia); patchy (type Ib); and bandlike (type Ic). In 12 fractures of 3 to 5 months after trauma, six showed focal hypointensity (type II) in all pulse sequences, and six showed isointensity (type IV). Four of 51 fractures with trauma over 5 months showed focal hyperintensity on T1-weighted images and isointensity on T2-weighted images (type III); and the remaining 47 fractures showed isointensity on all sequences (type IV). In conclusion, MR imaging is useful in predicting the age of known traumatic compression fractures, so familiarity with these sequential MR findings would be helpful in distinguishing benign from malignant fractures.
PMCID: PMC3054111  PMID: 8527045
8.  Alternate use of divergent forms of an ancient exon in the fructose-1,6-bisphosphate aldolase gene of Drosophila melanogaster. 
Molecular and Cellular Biology  1992;12(2):773-783.
The fructose-1,6-bisphosphate aldolase gene of Drosophila melanogaster contains three divergent copies of an evolutionarily conserved 3' exon. Two mRNAs encoding aldolase contain three exons and differ only in the poly(A) site. The first exon is small and noncoding. The second encodes the first 332 amino acids, which form the catalytic domain, and is homologous to exons 2 through 8 of vertebrates. The third exon encodes the last 29 amino acids, thought to control substrate specificity, and is homologous to vertebrate exon 9. A third mRNA substitutes a different 3' exon (4a) for exon 3 and encodes a protein very similar to aldolase. A fourth mRNA begins at a different promoter and shares the second exon with the aldolase messages. However, two exons, 3a and 4a, together substitute for exon 3. Like exon 4a, exon 3a is homologous to terminal aldolase exons. The exon 3a-4a junction is such that exon 4a would be translated in a frame different from that which would produce a protein with similarity to aldolase. The putative proteins encoded by the third and fourth mRNAs are likely to be aldolases with altered substrate specificities, illustrating alternate use of duplicated and diverged exons as an evolutionary mechanism for adaptation of enzymatic activities.
Images
PMCID: PMC364295  PMID: 1732743

Results 1-9 (9)