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Biomedical subjects

Paul S Kim

Publications and source records attributed to Paul S Kim.

6 recordsLinked to original sources

Oxidoreductase interactions include a role for ERp72 engagement with mutant thyroglobulin from the rdw/rdw rat dwarf.

Newly synthesized thyroglobulin (Tg), the secretory glycoprotein that serves as precursor in thyroid hormone synthesis, normally forms transient covalent protein complexes with oxidoreductases of the endoplasmic reticulum (ER). The Tg-G2320R mutation is responsible for congenital hypothyroidism in rdw/rdw rats, in which a lack of secondary thyroid enlargement (goiter) implicates death of thyrocytes as part of disease pathogenesis. We found that mutant Tg-G2320R was retained within the ER with no detectable synthesis of thyroxine, had persistent exposure of free cysteine thiols, and was associated with activated ER stress response but incomplete ER-associated degradation (ERAD). Tg-G2320R associated with multiple ER resident proteins, most notably ERp72, including covalent Tg-ERp72 interactions. In PC Cl3 thyrocytes, inducible overexpression of ERp72 increased the ability of cells to maintain Tg cysteines in a reduced state. Noncovalent interactions of several ER chaperones with newly synthesized Tg-G2320R diminished over time in parallel with ERAD of the mutant protein, yet a small ERAD-resistant Tg fraction remained engaged in covalent association with ERp72 even 2 days post-synthesis. Such covalent protein aggregates may set the stage for apoptotic thyrocyte cell death, preventing thyroid goiter formation in rdw/rdw rats.

Animals↗

Timing of peak bone mass: discrepancies between CT and DXA.

CONTEXT: The time of life in which peak bone mass in the axial skeleton is attained has been the subject of considerable controversy, with estimates ranging from the time of sexual and skeletal maturity to the fifth decade of life. OBJECTIVE: The objective was to examine whether dual energy x-ray absorptiometry (DXA) and computed tomography (CT) values for bone mass and bone density (BD) in the axial skeleton increase after sexual and skeletal maturity. DESIGN/PARTICIPANTS: Measurements of vertebral bone mineral density and bone mineral content (BMC) by DXA and vertebral BD and BMC by CT were obtained in 50 sexually and skeletally mature white females at baseline and 3 yr later. CT BMC values were calculated through analysis of vertebral volume in relation to density (BMC = vertebral volume x BD). RESULTS: Although neither CT BD nor BMC measures changed with time, DXA bone mineral density and BMC values were significantly higher at follow-up (P < 0.0001). Despite strong correlations between DXA and CT bone measures, DXA yielded greater changes in bone values in 47 of 50 subjects. CONCLUSIONS: Bone acquisition in the lumbar spine as measured by CT reaches its peak by sexual and skeletal maturity. In contrast, bone values by DXA continue to increase after puberty and cessation of longitudinal growth. Increases in DXA measures are likely a reflection of inhomogeneous changes in soft tissues around the spine or of disproportionate increases in the posterior elements of the vertebrae rather than of changes within the vertebral body.

Absorptiometry, Photon↗

Fat mass is not beneficial to bone in adolescents and young adults.

CONTEXT: Although muscle mass is beneficial to bone, studies on the effect of fat mass on bone have yielded conflicting results. OBJECTIVE: The aim of this study was to assess the relations between lean and fat mass and bone structure. DESIGN: This study was cross-sectional. SETTING: The study was conducted in a general community. SUBJECTS: Subjects included 300 healthy sexually mature adolescents and young adults (150 males and 150 females) between the ages of 13 and 21 yr. MAIN OUTCOME MEASURE: We investigated the relation between dual-energy x-ray absorptiometry (DXA) measures of total body fat and lean mass and bone values obtained with DXA (legs and lumbar spine bone mineral density and bone mineral content) and computed tomography (CT) (cross-sectional and cortical bone areas of the femurs and cross-sectional area and cancellous bone density of the vertebrae). RESULTS: Simple and multiple linear regression analyses showed significant positive relations between DXA lean mass and all CT and DXA measures of bone in the axial and appendicular skeletons (all P < 0.005). In contrast, whereas Pearson correlations between DXA measures of fat mass and bone parameters were generally positive, multiple regression analyses showed that fat mass, after accounting for lean mass, trunk height/leg length, had a negative, or no, correlation with CT and DXA values for bone. CONCLUSIONS: Our findings provide compelling evidence that, despite increased mechanical loading and independent of lean mass, adipose tissue is not beneficial to bone structure.

Absorptiometry, Photon↗

Lieposuction.

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Clinical Competence↗

Ligand-regulated secretion of recombinant annexin V from cultured thyroid epithelial cells.

The exposure of anionic phospholipids on the external surface of injured endothelial cells and activated platelets is a primary biological signal to initiate blood coagulation. Disease conditions that promote the formation of ectopic thrombi result in tissue ischemia. Annexins, Ca2+-dependent anionic phospholipid binding proteins, are potential therapeutic agents for the inhibition of coagulation. We have designed a transgene that targets secretion of annexin V from cultured thyroid cells under the control of doxycycline. Our results indicate that annexin V in the endoplasmic reticulum (ER)/Golgi lumen does not affect the synthesis, processing, and secretion of thyroglobulin. ER luminal Ca2+ was moderately increased and can be released by inositol 1,4,5-trisphosphate. Our study demonstrates that targeting and secretion of annexin V through the secretory pathway of mammalian cells does not adversely affect cellular function. Regulated synthesis and release of annexin V may exert anticoagulatory and anti-inflammatory effects systemically and may prove useful in further developing therapeutic strategies for conditions including antiphospholipid syndrome.

Amino Acid Sequence↗

A modified YMCA bench press test as a predictor of 1 repetition maximum bench press strength.

This study evaluated the influence of cadence on the Young Men's Christian Association (YMCA) bench press test for predicting 1 repetition maximum (1RM) bench press test performance. Fifty-eight medical students (37 men, 21 women) were evaluated for anthropometric variables (age, height, weight, fat-free mass, and percent fat), 1RM bench press, and 2 cadence tests of muscular endurance performed at cadences of 30 and 60 repetitions per minute (reps.min(-1)). Each test was performed on a separate day, with 5 days rest in between. There was no significant difference among the number of repetitions performed at each cadence by men, whereas women performed significantly more repetitions at the slower cadence. Repetitions at either cadence were good predictors of 1RM bench press in both genders (men: 30 reps.min(-1), r(2) = 0.757, standard error of the estimate [SEE] = 8.0 kg; 60 reps.min(-1), r(2) = 0.884, SEE = 8.2 kg; women: 30 reps.min(-1), r(2) = 0.754, SEE = 3.1 kg; 60 reps.min(-1), r(2) = 0.816, SEE = 2.7 kg). The addition of anthropometric dimensions to the regression equations did not improve predictive accuracy. Using both fast and slow cadences, the YMCA bench press test can provide a valid estimation of 1RM performance in untrained young men and women.

Adult↗