Corrective Surgery for a Forearm Deformity in a Middle-Aged Patient with Multiple Hereditary Exostoses: A Case Report.

CASE: A 48-year-old man underwent corrective surgery for a deformity of the left forearm because of multiple hereditary exostoses (MHE). The patient had no complaint of pain, the appearance of his forearm improved, and acceptable range of motion of the wrist and forearm were maintained at 14-month follow-up. CONCLUSION: The esthetic forearm deformity in the middle-aged patient with MHE was successfully improved without sacrificing function. Although there is little evidence of forearm corrective surgeries for adult patients with MHE, this report could expand surgical indications for them.

A multispecific monoclonal antibody G2 recognizes at least three completely different epitope sequences with high affinity.

A monoclonal antibody (mAb) G2 possesses an unusual characteristic of reacting with at least three proteins (ATP6V1C1, SEPT3, and C6H10orf76) other than its original antigen, chicken prion protein (ChPrP). The epitopes on ChPrP and ATP6V1C1 have been identified previously. In this study, we identified the epitope in the third protein, SEPT3. Interestingly, there was no amino acid sequence similarity among the epitopes on the three proteins. These epitopes had high binding affinities to G2 (KD = ∼10-7 M for monovalent binding and KD = ∼10-9 M for divalent binding), as determined using a SPR biosensor. This is the first report on a three-in-one mAb recognizing completely different epitope sequences with high affinity. Additionally, competitive ELISA indicated that the binding sites on G2, specific for the three different epitopes, overlapped, suggesting that the antigen-binding site may be flexible in the free form and capable of adapting to at least three different conformations to enable interactions with three different antigens.

Light-chain residue 95 is critical for antigen binding and multispecificity of monoclonal antibody G2.

The monoclonal antibody, G2, specifically binds to the immunogen peptide derived from the chicken prion protein, Pep18mer, and two chicken proteins derived peptides, Pep8 and Pep395; G2 binds with equal affinity to Pep18mer. The amino acid sequences of the three peptides are completely different, and so the recognition mechanism of G2 is unique and interesting. We generated a single-chain Fv (scFv) antibody of G2, and demonstrated its correct folding with an antigen binding function similar to intact G2 antibody. We also generated a Pro containing mutant of G2 scFv at residue 95 of the light chain, and analyzed its antigen binding using a surface plasmon biosensor. The mutant lost its binding ability to Pep18mer, but remained those to Pep8 and Pep395. The results clearly indicate residue 95 as being critical for multispecific antigen binding of G2 at the site generated from the junctional diversity introduced at the joints between the V and J gene segments.

First observation of metal ion-induced structural fluctuations of α-helical peptides by using diffracted X-ray tracking.

In order to analyze protein structural dynamics, we designed simple model peptides whose structures changed from random-coil to helix-bundle structures by forming stable hydrophobic core in the presence of metal ions. The strategy involved destabilizing a de novo designed three helix-bundle protein by substituting the residues present in its hydrophobic core with histidine and small amino acids. The conformational changes of peptides induced upon binding of Zn2+ to histidine were analyzed using circular dichroism spectroscopy, which revealed peptides, HA and HG, to be good candidates for further analyses. The diffracted X-ray tracking experiments showed that the structural fluctuations of both HA and HG were suppressed upon binding of Zn2+. We succeeded in observing the differences in fluctuations of HA and HG in solution between random-coil like and helix-bundle structures. The metal-binding energies determined using the angular diffusion coefficients were in good agreement with those determined using isothermal titration calorimetry.

Cyclophilin-D inhibition in neuroprotection: dawn of a new era of mitochondrial medicine.

Traumatic brain injury and ischemia can result in marked neuronal degeneration and residual impairment of cerebral function. However, no effective pharmacological treatment directed at tissues of the central nervous system (CNS) for acute intervention has been developed. The detailed pathophysiological cascade leading to -neurodegeneration in these conditions has not been elucidated, but cellular calcium overload and mitochondrial dysfunction have been implicated in a wide range of animal models involving degeneration of the CNS. In particular, activation of the calcium-induced mitochondrial permeability transition (mPT) is considered to be a major cause of cell death inferred by the broad and potent neuroprotective effects of -pharmacological inhibitors of mPT, especially modulators of cyclophilin activity and, more specifically, genetic inactivation of the mitochondrial cyclophilin, cyclophilin D. Reviewed are evidence and challenges that could bring on the dawning of mitochondrial medicine aimed at safeguarding energy supply following acute injury to the CNS.

[Organ protective effects of volatile anesthetics and perioperative outcomes].

Anesthetic agents, especially, volatile anesthetics are considered to exert organ toxicity such as nephrotoxicity and hepatotoxicity; however, recent aggressive researches explored the beneficial effects of volatile anesthetics as an organ protectant. Ischemic preconditioning is a phenomenon in which single or multiple brief periods of ischemia have been shown to protect the myocardium and brain against prolonged ischemic insult. General anesthesia showed the protection against both ischemic myocardial and brain reperfusion injuries. This phenomenon is called anesthetic preconditioning. Regarding the organ protection, anesthetic preconditioning is one of the useful ways to diverse the organ protective effects not only to heart but also brain. Nowadays, ischemic postconditioning, consisting of repeated brief cycles of ischemia-reperfusion performed immediately after reperfusion following a prolonged ischemic insult, dramatically reduces infarct size in experimental models and such clinical studies are reported. Both preconditioning and postconditioning share the same signal transduction pathway and inhibit the mitochondrial permeability transition (MPT) that leads to either apoptosis or necrosis of myocardium and neuronal cell. Both phenomena look very promising, but we still lack the real evidence for human reserach in terms of the clinical outcome and further analysis is necessary. Neurotoxicities of anesthetic agents are very crucial problems for the patient and they are considered to be due to the activation of IP3 receptor in ER after exposure to volatile anesthetics. Massive release of Ca2+ from ER induces Ca2+ overload leading to mitochondria permeability transition (MPT) and induces apoptosis in the brain or aggravates the neurodegenerative disease. Susceptible mechanisms and beneficial treatment for the toxicity of general anesthesia is considered as a critical subject to discuss and challenge to solve for our future.