Studies on anti-von Willebrand factor (vWF) monoclonal antibody NMC-4, which inhibits both ristocetin- and botrocetin-induced vWF binding to platelet glycoprotein Ib

Anti-von Willebrand factor (vWF) monoclonal antibody NMC-4 completely inhibited vWF binding to platelet glycoprotein (GP) lb induced by either ristocetin or botrocetin at an IgG concentration of approximately 10 micrograms/mL, and also blocked binding of asialo-vWF to GP lb. NMC-4 coupled beads isolated a 97-Kd fragment (Fr) from a whole tryptic digest of vWF. The N-terminal sequencing of the nonreduced 97-Kd Fr, in combination with amino acid analysis, showed it to be a homodimer of residues 449 through 728 of the constituent subunit. Present data, together with the results obtained from previous studies, confirm the existence of one or three possible inter-subunit disulfide bonds between cysteine residues 459, 462, and 464. NMC-4 bound to reduced vWF Fr(s) more weakly than to nonreduced Fr(s), but it did not react with Fr III-T2 of vWF, a disulfide-linked twin heterodimer of residues 273 through 511 and 674 through 728 (Marti et al, Biochemistry 26:8099, 1987). Fr III-T2 completely inhibited ristocetin-induced vWF binding at a concentration of 100 mumol/L but had no effect on botrocetin-induced binding. In addition, both the N- and C-terminal polypeptides, residues 449 through 549 and 674 through 728, generated by subdigestion of the 52/48-Kd Fr (Fujimura et al, J Biol Chem 261:381, 1986), inhibited preferentially ristocetin-induced vWF binding without affecting to botrocetin-induced vWF binding. These findings suggest that amino acid residues 512 through 673 of the vWF subunit are involved in botrocetin-induced vWF binding.     

Investigation of the prognosis of patients with papillary thyroid carcinoma by tumor size

In papillary thyroid carcinoma (PTC), extrathyroid extension (Ex) and clinical lymph node metastasis (N) significantly affect the prognosis. We investigated the prognosis of patients with PTC 1 cm or less (1,220 patients), 1.1-2 cm (2,101 patients), 2.1-3 cm (1,249 patients), 3.1-4 cm (645 patients), and larger than 4 cm (563 patients). We classified N factor into three categories: N0, no clinical node metastasis: N1, clinical node metastasis smaller than 3 cm and without extranodal tumor extension requiring at least partial excision of adjacent organs for node dissection: and N2, clinical node metastasis 3 cm or larger or showing extranodal tumor extension. N2 markedly affected lymph node and distant recurrence-free survivals and cause-specific survival, regardless of the tumor size. N1 also adversely affected lymph node and distant recurrence-free survival but not cause-specific survival. Ex did not affect patients' prognosis with PTC 1 cm or less. It became a prognostic factor with PTC larger than 1 cm, and worsened lymph node and distant recurrence-free survival not only for N0 but also for N1 PTC larger than 3 cm and larger than 2 cm, respectively. However, its influence is limited for N2 PTC patients. Furthermore, Ex worsened the CSS with PTC larger than 2 cm in combination with N2. We have to note that the prognostic significance for lymph node and distant recurrence-free and cause-specific survival of Ex and N varies according to the tumor size in order to accurately predict the clinical outcomes and establish therapeutic strategies for PTC patients.     

Butyrylcholinesterase level as an independent prognostic factor for overall survival in patients on maintenance hemodialysis: a single-center retrospective study

Clinical and Experimental Nephrology - We investigated whether butyrylcholinesterase (BChE) was independently related to the overall survival (OS) of patients on maintenance hemodialysis (MHD)....     

Coronary artery calcium score and CT angiography in asymptomatic elderly patients with high pretest probability for coronary artery disease

Purpose

To evaluate the role of coronary artery calcium scoring (CACS) and/or coronary CT angiography (CCTA) in asymptomatic elderly patients with high pretest probability for coronary artery disease (CAD).

Materials and methods

Forty-eight consecutive asymptomatic elderly (>65 years) subjects who had a high pretest probability and underwent CACS/CCTA were included. Each CCTA was evaluated for adequacy for assessment of coronary stenosis. Significant stenosis (>50 % diameter narrowing) was assessed on evaluable CT images and by invasive catheter angiography (ICA).

Results

All subjects were men with mean CACS of 880 ± 1779. Among those with low (0–99), intermediate (100–399), and high (400–999) CACS, ICA-verified significant stenosis was present in 8 % (1/13), 23 % (2/13), and 67 % (8/12), respectively. Among those with very high CACS (≥1000) (n = 10), 90 % of CCTAs were not evaluable for stenosis.

Conclusion

In asymptomatic elderly subjects with high pretest probability, CACS followed by CCTA may be considered for those with intermediate to high CACS.