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Biomedical subjects

Christian Head

Publications and source records attributed to Christian Head.

6 recordsLinked to original sources

Coengagement of CD16 and CD94 receptors mediates secretion of chemokines and induces apoptotic death of naive natural killer cells.

Down-modulation of CD16 (FcgammaRIII) receptors and loss of natural killer (NK) cell function have been observed in oral cancer patients. However, neither the mechanisms nor the significance of the decrease in CD16 receptors have been fully understood. The cytotoxic activity and survival of NK cells are negatively regulated by antibodies directed against CD16 surface receptor. The addition of anti-CD94 antibody in combination with either F(ab')(2) fragment or intact anti-CD16 antibody to NK cells resulted in significant inhibition of NK cell cytotoxic function and induction of apoptosis in resting human peripheral blood NK cells. Addition of interleukin-2 to anti-CD16 and/or anti-CD94 antibody-treated NK cells significantly inhibited apoptosis and increased the function of NK cells. There was a significant increase in tumor necrosis factor-alpha (TNF-alpha) but not IFN-gamma secretion in NK cells treated either with anti-CD16 antibody alone or in combination with anti-CD94 antibodies. Consequently, the addition of anti-TNF-alpha antibody partially inhibited apoptosis of NK cells mediated by the combination of anti-CD94 and anti-CD16 antibodies. Increase in apoptotic death of NK cells also correlated with an increase in type 2 inflammatory cytokines and in the induction of chemokines. Thus, we conclude that binding of antibodies to CD16 and CD94 NK cell receptors induces death of the NK cells and signals for the release of chemokines.

Antibodies, Monoclonal↗

Hypericin and pulsed laser therapy of squamous cell cancer in vitro.

OBJECTIVE: This in vitro study compares continuous wave and pulsed laser light at longer wavelengths for activation of the phototoxic drug hypericin in human cancer cells. BACKGROUND DATA: Two-photon pulsed laser light now allows high-resolution fluorescent imaging of cancer cells and should provide deeper tissue penetration with near infrared light for improved detection as well as phototoxicity in human tumors. METHODS: Cultured Seoul National University (SNU)-1 tumor cells from a squamous cell carcinoma (SCC) were incubated with hypericin before photoirradiation at four laser wavelengths. Phototoxicity of hypericin sensitized SCC cells was measured by dimethyl thiazoldiphenyl (MTT) tetrazolium bromide cell viability assays and by confocal fluorescence microscopy via 532-nm and infrared two-photon pulsed laser light. RESULTS: Phototoxic response increased linearly with hypericin dose of 0.1-2 microM, light exposure time of 5-120 sec, and pulsed dye laser wavelengths of 514-593 nm. Light energy delivery for 50% cell phototoxicity (LD50) response was 9 joules at 514 nm, 3 joules at 550 nm, and less than 1 joule at the 593 nm hypericin light absorption maxima. Fluorescence confocal microscopy revealed membrane and perinuclear localization of hypericin in the SNU cells with membrane damage seen after excitation with visible 532 nm continuous wave light or two-photon 700-950 nm picosecond pulsed laser irradiation. CONCLUSIONS: Hypericin may be a powerful tumor targetting drug when combined with pulsed laser light in patients with recurrent head and neck SCC.

Anthracenes↗

Useful landmarks in arytenoid adduction and laryngeal reinnervation surgery.

OBJECTIVE: Knowledge of the location of the muscular process of the arytenoid cartilage and the recurrent laryngeal nerve is essential to performing a successful arytenoid adduction and laryngeal reinnervation surgery. We describe external landmarks useful in locating these structures. STUDY DESIGN: Cadaveric laryngeal dissection. METHODS: Posterior laryngeal dissection was performed in 16 human larynges. The position of the muscular process of the arytenoid was measured bilaterally relative to the inferior and superior borders of the thyroid lamina. The recurrent laryngeal nerve was followed distally from slightly below the level of the cricothyroid joint to its genu where its vertical course changes to an oblique intralaryngeal course. RESULTS: The muscular process of the arytenoid was usually found halfway between the roots of the superior and inferior cornu of the thyroid lamina. The recurrent laryngeal nerve was found just deep to the cricothyroid joint and lateral to the posterior cricoarytenoid muscle. There were no other nerves in this area. CONCLUSIONS: This study finds that the superior and inferior borders of the thyroid lamina are useful intraoperative landmarks to locate the muscular process of the arytenoid. The cricothyroid joint provides a good starting point to locate the recurrent laryngeal nerve, which can be identified slightly deeper between it and the posterior cricoarytenoid muscle.

Adolescent↗

Lamina propria replacement therapy with cultured autologous fibroblasts for vocal fold scars.

OBJECTIVES: To develop a canine model of vocal fold scar and to evaluate its treatment with lamina propria replacement therapy using autologous cultured fibroblasts. MATERIALS AND METHODS: Full thickness of the lamina propria layer in canine vocal folds was injured with a laser. Fibroblasts were cultured and expanded in the laboratory from a buccal mucosal biopsy. The scarred vocal folds were treated with 3 weekly injections of fourth, fifth, and sixth passage autologous fibroblasts. Mucosal waves and acoustic parameters were measured at baseline, after scarification, and several months after injection therapy. Histologic evaluation of the vocal folds for fibroblasts, collagen, elastin, reticulin, and hyaluronic acid was performed. RESULTS: Nine beagle dogs were used, and 1 animal served as control. Vocal fold scarring resulted in absent or severely limited mucosal waves and significantly worse acoustic parameters. Significant improvements in mucosal waves and acoustic parameters were obtained after lamina propria replacement therapy. After therapy, mucosal waves became normal in 4 animals and near normal in the other 4. No statistical difference was found in mucosal waves between baseline and post-therapy. All animals tolerated therapy without complications. The treated vocal folds demonstrated an increased density of fibroblasts, collagen, and reticulin, a decreased density of elastin, and no change in hyaluronic acid. CONCLUSIONS AND SIGNIFICANCE: Therapeutic options for vocal fold scars are limited. Lamina propria replacement therapy in the form of autologous cultured fibroblasts improves mucosal pliability and returns normal or near normal mucosal waves in experimentally scarred vocal folds. This novel therapeutic modality may hold new promise for treating vocal fold scars.

Animals↗

Microvascular flap reconstruction of the mandible: a comparison of bone grafts and bridging plates for restoration of mandibular continuity.

OBJECTIVE: To compare the efficacy of vascularized bone grafts and bridging mandibular reconstruction plates for restoration of mandibular continuity in patients who undergo free flap reconstruction after segmental mandibulectomy. Study design and setting A total of 210 patients underwent microvascular flap reconstruction after segmental mandibulectomy. The rate of successful restoration of mandibular continuity in 151 patients with vascularized bone grafts was compared to 59 patients with soft tissue free flaps combined with bridging plates. RESULTS: Mandibular continuity was restored successfully for the duration of the follow-up period in 94% of patients who received bone grafts compared with 92% of patients with bridging mandibular reconstruction plates. This difference was not statistically significant. In patients who received bone grafts, most cases of reconstructive failure occurred during the perioperative period and were due to patient death or free flap thrombosis. In patients who received bridging plates, all instances of reconstructive failure were delayed for several months and were due to hardware extrusion or plate fracture. CONCLUSIONS: Vascularized bone-containing free flaps are preferred for reconstruction of most segmental mandibulectomy defects in patients undergoing microvascular flap reconstruction. However, use of a soft tissue flap with a bridging mandibular reconstruction plate is a reasonable alternative in patients with lateral oromandibular defects when the nature of the defect favors use of a soft tissue free flap. SIGNIFICANCE: Both bone grafts and bridging plates represent effective methods of restoring mandibular continuity following segmental mandibulectomy, with the former being the preferred technique for patients undergoing microvascular reconstruction.

Adult↗

Microvascular reconstruction after previous neck dissection.

BACKGROUND: Microvascular reconstruction of defects in the head and neck is more challenging in patients who have undergone a previous neck dissection, owing to prior resection of potential cervical recipient blood vessels used for free flap perfusion. OBJECTIVE: To evaluate the reliability and safety of free flap reconstruction in patients with previous neck dissection. PATIENTS AND METHODS: Sixty free flaps were performed in 59 patients with a medical history of neck dissection for head and neck cancer. This included patients undergoing salvage surgery for recurrent cancer as well as patients undergoing secondary reconstruction of cancer surgery-related defects. Flap selection included 25 radial forearm flaps, 20 fibula flaps, 7 rectus abdominis flaps, 7 subscapular system flaps, and 1 iliac crest flap. RESULTS: Recipient vessels were used in the field of previous neck dissection in approximately half the patients with previous selective neck dissection, while contralateral recipient vessels were always used in patients with a history of modified radical or radical neck dissection. Vein grafts were not necessary in any cases. One arterial anastomosis that was created under excessive tension required urgent reoperation and revision, but there were no cases of free flap failure. CONCLUSIONS: Free flap reconstruction of the head and neck is highly successful in patients with a history of neck dissection, despite a relative paucity of potential cervical recipient blood vessels. Heavy reliance on free flaps with long vascular pedicles obviated the need to perform vein grafts in the present series, probably contributing to the absence of free flap failure. Previous neck dissection should not be considered a contraindication to microvascular reconstruction of the head and neck.

Adult↗