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Biomedical subjects

Ko Hosokawa

Publications and source records attributed to Ko Hosokawa.

At least 19 recordsLinked to original sources

The Rho-associated kinase inhibitor fasudil hydrochloride enhances neural regeneration after axotomy in the peripheral nervous system.

BACKGROUND: The Rho family of small GTPases is responsible for various processes involving actin cytoskeleton in eukaryotic cells, including neurite outgrowth. Several substances found at the peripheral nerve injury site were shown to activate one member of this family, Rho. The activation of Rho leads to neurite outgrowth inhibition and the development of posttraumatic neuropathic pain. The authors used the clinically tested Rho-associated kinase inhibitor fasudil hydrochloride to enhance the functional recovery of the peripheral nerve in the rat. METHODS: In the peroneal nerve interpositional graft model, the authors administered fasudil (experimental groups) or saline (control groups) (1) intraperitoneally and (2) directly into the graft by microinjection (n = 6 animals per experimental condition). Neural recovery was assessed during postoperative follow-up lasting 80 days by peroneal functional index, electrophysiologic, and histomorphometric analyses. RESULTS: The peroneal functional index returned to values not significantly different from preoperative values on days 55 (fasudil injected into the graft) and 60 (fasudil injected intraperitoneally) in the experimental groups. In the control groups, this took 70 (saline injected intraperitoneally) and 75 days (saline injected into the graft). These results are supported by electrophysiologic and histomorphologic assessments. CONCLUSIONS: The authors determined that fasudil hydrochloride was capable of accelerating the functional regeneration after peripheral nerve axotomy, which is consistent with the results of reports about Rho cascade disruption in the central nervous system. Because fasudil hydrochloride is a clinically tested drug, it could be used to enhance neural regeneration in human patients as well.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗

p21Cip1/WAF1 regulates radial axon growth and enhances motor functional recovery in the injured peripheral nervous system.

Recent studies have provided evidence that p21Cip1/WAF1 has not only cell cycle-associated activities but also other biological activities like neurite elongation. To investigate the role of p21Cip1/WAF1 in the in vivo axonal regeneration in the peripheral nervous system, we developed a p21Cip1/WAF1 knockout (KO) mice sciatic nerve injury model. We performed quantitative assessments of the functional, histological, and electrophysiological recoveries after sciatic nerve injury in p21Cip1/WAF1 KO mice and compared the results with those of the wild-type mice. p21Cip1/WAF1 KO mice showed a significant delay of the motor functional recovery between 21 and 42 days after sciatic nerve injury. The values of motor conduction velocity in p21Cip1/WAF1 KO mice were significantly lower than those in the wild-type mice on postoperative day 28. The mean percent neural tissue and the mean nerve axon width of p21Cip1/WAF1 KO mice were significantly less than those of the wild-type mice, which was caused by hyperphosphorylation of neurofilaments. Therefore, p21Cip1/WAF1 was considered to be involved in radial axon growth and to be essential for the motor functional recovery following peripheral nervous system injury.

Animals↗

Use of calcium phosphate cement paste in orbital volume augmentation.

BACKGROUND: The development of calcium phosphate in cement paste form has made its application simplified and easy. In this study, the authors used an alpha-tricalcium phosphate/dicalcium phosphate dibasic/tetracalcium phosphate monoxide/hydroxyapatite injectable calcium phosphate cement paste to evaluate its potential use in orbital volume augmentation. METHODS: Five New Zealand white rabbits were used in this study. In each rabbit, the right orbit was directly implanted with calcium phosphate cement in its injectable paste form, and a prehardened form was placed in the left orbit. The orbital roof was approached through a subciliary skin incision and the implant was placed posterior to the globe of the eyeball to push it outward. Measurement of proptosis and intraocular pressure was monitored before and after implantation. The animals were killed after 3 months, and orbit bone-implant samples were taken for histology and microradiography. RESULTS: In both groups, proptosis was induced, 4.2 +/- 0.27 mm in the prehardened group and 3.8 +/- 0.22 mm in the injectable group. These values taken 1 week postimplantation were unchanged until the end of the experiment and were maintained without significant intraocular pressure changes. The implants were well tolerated, and no sign of infection, extrusion, or migration was noted. Histologic analysis showed good biocompatibility and osteoconductivity, and microradiography has confirmed a well-set cement with direct bone union to it. CONCLUSION: These findings therefore indicate that calcium phosphate cement implant, when used as an injectable paste or in its prehardened form, can be a safe, effective material for orbital volume augmentation.

Animals↗

Soft palate mucosal adhesion as a preparation for Furlow's double-opposing Z-palatoplasty.

BACKGROUND: Furlow's double-opposing Z-palatoplasty enables both soft palate lengthening and palatal muscle reorientation, and outstanding speech results have been reported. However, Z-plasty often results in horizontal stress and requires relaxing incisions in some cases. This article presents the authors' novel two-stage Furlow double-opposing Z-palatoplasty used in 13 cleft lip-cleft palate patients. METHODS: During cheiloplasty, partial soft palate adhesion was performed. Only mucosal tissue was approximated to prevent damage to the palatal muscle. The residual palatal cleft decreased gradually, and palatoplasty was scheduled at the age of 1 year. Adhesive soft palate tissue was incised and Furlow's double-opposing Z-palatoplasty was performed in the usual manner. RESULTS: Eleven patients underwent Furlow's palatoplasty without relaxing incisions, and in two patients relaxing incisions were required along the inside of the alveolus. Relaxing incisions around the maxillary tuberosities were not required in any of the 13 cases. Analysis of the palatal cast models was carried out on the adhesion group (n = 13) and the control group (n = 9). In both groups, the mean distance between the tuberosities increased, and cleft widths at the alveolus and the middle of the hard palate were decreased. Furthermore, cleft width at the junction of the hard and soft palates was decreased significantly in the adhesion group compared with the control group. CONCLUSIONS: As a preparation for Furlow's palatoplasty, soft palate adhesion induced a decrease of cleft width without interfering with the transverse growth of the posterior maxilla and enabled Z-plasty of an adequate size without relaxing incisions.

Cleft Lip↗

Dual segmental distraction osteogenesis of the midface in a patient with Apert syndrome.

OBJECTIVE: To present orthodontic treatment combined with dual segmental distraction osteogenesis in a patient with Apert syndrome. PATIENT: A 15-year-old boy exhibited severe midfacial hypoplasia with retruded and hypoplastic maxilla and anterior open bite. The patient was treated with a rigid external distraction II system for distraction osteogenesis, a preadjusted edgewise appliance, and a modified maxillary protraction headgear. The concave profile with midfacial hypoplasia was improved. A tight occlusal relationship between maxillary and mandibular teeth was achieved. Postoperative treatment results have been stable for 1 year.

Acrocephalosyndactylia↗

Combined tongue flap and V-Y advancement flap for lower lip defects.

A combined tongue flap and V-Y advanced flap were used for reconstruction of the lower lip after radical excision of squamous cell carcinoma. This V-Y advancement flap is useful because the procedure does not require any difficult technique, and preservation of the orbicularis oris muscle and the branch of the mental artery and nerve are possible. The vermilion is reconstructed with a tongue flap, with almost no disturbance in the patients' speaking or eating and satisfactory cosmetic results. We describe this procedure in two cases.

Aged↗

End-to-side nerve grafts: experimental study in rats.

The effectiveness of the end-to-side nerve graft in comparison with the end-to-end cable-graft was determined in rat sciatic nerve transection models. Sixty Sprague-Dawley rats were randomly divided into four groups with different reconstructive methods for two branches of the sciatic nerve: Group I, median nerve graft with end-to-side neurorrhaphy; Group II, median and ulnar nerve grafts with end-to-end neurorrhaphy; Group III, no repair; and Group IV, sham operation. Between Groups I and II, there were no significant differences in the functional, electrophysiologic, and histologic evaluations. In retrograde tracing of the spinal cord and dorsal root ganglia, the number of double-labeled neurons was significantly higher in Group I. End-to-side nerve grafts show good functional recovery, require less graft, and are easy to perform. The authors find this method to be an effective alternative in facial nerve reconstruction and of great value in various kinds of peripheral nerve surgery.

Anastomosis, Surgical↗

A simple method for auricular reconstruction in mild cases of conchal type microtia.

The authors describe their method of helix/antihelix creation together with their algorithm of mild conchal type microtia treatment. In mild cases of conchal type microtia, they do not use a platform-based framework but fabricate the helix and the antihelix separately from costal cartilage and anchor them firmly into the corrected remnant concha. A framework created in this way is sufficiently supportive for the new ear, has good aesthetic features, and is fast and easy to fabricate. Moreover, because the procedure does not require a large amount of cartilage, it also decreases the occurrence of donor-site complications. The authors present a group of 45 patients with a total of 47 reconstructed ears and follow-up periods of from 6 months to 6 years.

Adolescent↗

Changes in mRNA of Slit-Robo GTPase-activating protein 2 following facial nerve transection.

Complex processes following peripheral nerve injury integrate a number of various external cues and their intracellular responses resulting in the cytoskeletal remodeling. One of these cues, Slit protein, plays an important role in neuronal migration and axonal guidance through the interaction with Roundabout (Robo) receptor. It was reported that the signal from Robo is transmitted to a specific family of GTPase-activating proteins (GAPs) named Slit-Robo GAPs. The Slit-Robo GAPs (srGAPs) further transmit the signal to the actin cytoskeleton controlling Rho GTPases and thus provide a direct link between Slit-Robo signaling and actin cytoskeleton. We examined the effects of facial nerve transection on srGAP2 mRNA expression in the facial nerve nuclei by in situ hybridization. SrGAP2 mRNA was initially expressed, and its expression increased from 3 to 28 days after transection, with the peak at the seventh day after axotomy. The upregulation was found mostly in the neuronal cells and only to a small extent in the glial cells. Our results suggest that srGAP2, as a part of Slit-Robo pathway, plays an important role in the axonal regeneration after axotomy.

Animals↗

FLRT3, a cell surface molecule containing LRR repeats and a FNIII domain, promotes neurite outgrowth.

The mature peripheral nervous system has the ability to survive and to regenerate its axons following axonal injury. After nerve injury, the distal axonal and myelin segment undergoes dissolution and absorption by the surrounding cellular environment, a process called Wallerian degeneration. Using cDNA microarrays, we isolated FLRT3 as one of the up-regulated genes expressed in the distal segment of the sciatic nerve 7 days after transection relative to those of the intact sciatic nerve. FLRT3 is a putative type I transmembrane protein containing 10 leucine-rich repeats, a fibronectin type III domain, and an intracellular tail. The neurons plated on CHO cells expressing FLRT3 extended significantly longer neurites than those plated on wild-type CHO cells, demonstrating that FLRT3 promotes neurite outgrowth. FLRT3 mRNA was especially abundant in the basal ganglia, the granular layer of cerebellum, and the hippocampus, except the CA1 region in the adult rat brain. Thus, FLRT3 may contribute to regeneration following axonal injury.

Animals↗

Activation of Rho in the injured axons following spinal cord injury.

Axons of the adult central nervous system have very limited ability to regenerate after injury. This inability may be, at least partly, attributable to myelin-derived proteins, such as myelin-associated glycoprotein, Nogo and oligodendrocyte myelin glycoprotein. Recent evidence suggests that these proteins inhibit neurite outgrowth by activation of Rho through the neurotrophin receptor p75(NTR)/Nogo receptor complex. Despite rapidly growing knowledge on these signals at the molecular level, it remained to be determined whether Rho is activated after injury to the central nervous system. To assess this question, we establish a new method to visualize endogenous Rho activity in situ. After treatment of cerebellar granular neurons with the Nogo peptide in vitro, Rho is spatially activated and colocalizes with p75(NTR). Following spinal cord injury in vivo, massive activation of Rho is observed in the injured neurites. Spatial regulation of Rho activity may be necessary for axonal regulation by the inhibitory cues.

Animals↗

Simple repair of complex rectovaginal fistulas.

We describe a successful anterior rectal wall advancement flap in two patients with complex rectovaginal fistulas. Our technique used a wide transversely-incised flap, which ensures adequate blood supply, facilitates wide dissection, allows approximation of the anterior rectal wall without tension, and secures closure of the orifice of the fistula.

Adult↗

Arterial anatomy of the lower lip.

The arterial anatomy of the lower lip was investigated in 12 sides of six fresh cadavers that had been injected systemically with a lead oxide and gelatin mixture. We found that the blood supply of the lower lip was derived from the facial artery and three dominant labial arteries: the inferior labial artery, the horizontal labiomental artery, and the vertical labiomental artery. The inferior labial artery was derived from the facial artery or superior labial artery, and ran through the submucous tissue horizontally. The horizontal labiomental artery arising from the facial artery was located between the depressor labii inferioris muscle and orbicularis oris muscle. The vertical labiomental artery arose from the submental artery. These three arteries provided small vessels that traversed vertically. These small vessels and the small branches of the facial artery, that run superficial and deep to the orbicularis oris muscle, formed a vascular network in subcutaneous and submucous tissues and minute vessels branched off to the skin, mucosa, and muscles.

Angiography↗

Bronchogenic cyst of the shoulder.

An 8-month-old girl presented with a painless mass on her left shoulder that was noticed by her mother. Ultrasonography and magnetic resonance imaging (MRI) showed a well-defined subcutaneous cystic mass. The excised cyst was lined with ciliated pseudostratified columnar epithelium with occasional goblet cells and diagnosed as a bronchogenic cyst. She made a good recovery.

Bronchogenic Cyst↗

Arterial anatomical features of the upper palpebra.

The arterial anatomical features of the upper palpebra were examined in both sides of seven fresh cadavers that had been systemically injected with a lead oxide/gelatin mixture. All specimens were stereoscopically radiographed for analysis of the three-dimensional structure of the arteries and were macroscopically dissected for observation of the relationships between the arteries and the other tissues. Cross-sections were prepared from one specimen and examined histologically. In all cases, there were four arterial arcades in the upper palpebra, namely, the marginal, peripheral, superficial orbital, and deep orbital arcades. Each arcade provided small vertical branches. The vertical branches coursed on both sides of the orbicularis oculi muscle and on both sides of the tarsal plate. From these small vertical branches, fine vessels branched off to the skin, muscle, and tarsal plate. These findings are important for avoiding complications such as bleeding and are useful for designing local flaps, such as switch flaps, for reconstructive surgical procedures.

Angiography↗

Vascular anatomy of the anterolateral thigh flap.

Arterial and venous anatomy and their relation to the anterolateral thigh flap were examined in 10 specimens of six fresh cadavers in which radiopaque materials were injected into both the arterial and venous systems. Territories and positions of individual perforating arteries were measured, and the venous drainage pathway of the flap was analyzed. All specimens were radiographed stereoscopically to observe the three-dimensional structure of the arteries and veins. The territory of each perforating artery was smaller than expected. Most of the venous blood that had perfused the dermis was considered to pool in a polygonal venous network located in the skin layer and to enter the descending branch of the lateral circumflex femoral artery through large descending veins. The venous territories were considered different from the arterial territories. The findings in this study suggest that the design of the anterolateral thigh flap should be based on the venous architecture rather than on the arterial architecture and that the flap survival rate might be improved if thinning is performed appropriately.

Angiography↗

Orbital floor reconstruction using calcium phosphate cement paste: an animal study.

Orbital floor defects were created in 10 New Zealand white rabbits and were reconstructed using an injectable calcium phosphate paste. These animals were euthanized at 2, 4, 8, and 12 months after implantation and were examined for biocompatibility and osteoconductivity. Grossly, implants were found to be adherent to the floor and covered with fibrous tissues. There was no sign of infection, extrusion, or migration of implant within the orbit and maxilla. The orbital floor was completely restored. Histological examination showed active new bone formation that encroached within the implant and gradually increased in density with time. Maxillary mucosa and glands were likewise reconstituted. Thin fibrovascular tissues were seen on top of and within the surface of the implant, and few to slight inflammatory cells were seen. Microradiography showed direct apposition between the new bone and the implant. These findings compare favorably with previously published reports on the biocompatibility and osteoconductivity of calcium phosphate cement. The authors believe that, together with ease of use and structural integrity, calcium phosphate paste can be useful in orbital floor reconstruction.

Animals↗