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Biomedical subjects

Ko Hosokawa

Publications and source records attributed to Ko Hosokawa.

At least 37 records · Page 2Linked to original sources

Expression of FERM domain including guanine nucleotide exchange factor mRNA in adult rat brain.

FERM domain including Rho GEF (FIR) belongs to Dbl family of guanine nucleotide exchange factors and specifically activates biochemical pathways specific for Rac1. FIR was shown to regulate neurite remodeling of the embryonic neurons. Here we report a distribution of FIR mRNA in adult rat brain using in situ hybridization. The expression was found all throughout the brain with the most intensive signals in hippocampus, piriform cortex, red nucleus and nuclei of cranial nerves. The signal was predominantly localized in the neuronal cells.

Aging↗

Rat model of laryngeal transplantation with normal circulation maintained by combination with the tongue.

Recent research on laryngeal transplantation used a rat model with physiologically abnormal circulation, because the common carotid artery was used for venous drainage. Since a model with normal circulation is better for accurate assessment, we developed a vascularized laryngeal graft, using the common carotid artery as the arterial supply and the external jugular vein as the venous drainage. The transplant included other tributaries from the tongue and the pharynx by combination with the tongue, because the tributaries from the larynx were very small. Ten transplants were performed. The transplanted organs were examined daily. Seven days after transplantation, the composite grafts were evaluated histologically. The mortality rate was 10%. All composite grafts were fully viable, and their structure was maintained in the remaining nine rats. Our model is appropriate for experiments on laryngeal transplantation.

Animals↗

Skin-sparing mastectomy and immediate reconstruction with a deep inferior epigastric perforator flap.

BACKGROUND: It is important for breast reconstruction after mastectomy to recreate immediately good breast symmetry with an adequate amount of soft tissue. METHODS: Eight patients with breast cancer underwent skin-sparing mastectomy and immediate reconstruction with a deep inferior epigastric perforator flap. This operative technique, and the results, advantages, and disadvantages of the technique were assessed. RESULTS: Seven patients had stage IIA disease, and one patient had stage I disease. An arc-shaped incision was made just at the lateral border of the breast in all patients. Three patients had a separate periareolar incision, and one had a circumferential nipple incision. There was 100% flap survival, and good breast symmetry was achieved in all patients. No major perioperative complications occurred in this series. A small amount of fat necrosis occurred in one flap. One patient had slight abdominal bulging. Minor wound-healing problems at the lateral breast skin envelope occurred in two patients. CONCLUSION: These data indicate that skin-sparing mastectomy and immediate reconstruction with a DIEP flap is a reliable and safe technique. This method is a potentially useful surgical technique, which has achieved very promising results.

Adult↗

Nevus lipomatosus cutaneous superficialis of the clitoris.

BACKGROUND: Nevus lipomatosus cutaneous superficialis (NLCS) is a relatively rare condition. Although NLCS can affect any region of the entire body, no case of NLCS in the clitoris has ever been reported. OBJECTIVE: To report a case of NLCS of the clitoris that presented manifestations that were similar to female pseudohermaphrodism. METHODS: This is a case report and review of the literature. RESULTS: A congenital, soft, skin-colored lesion of the clitoris in a 1-year-old girl resembled female pseudohermaphrodism. It was resected, and the histologic diagnosis was NLCS. Postoperatively, there was no subsequent change in the lesion during the 3-year follow-up period. CONCLUSION: We reported a case of congenital solitary NLCS of the clitoris. Although NLCS might be a relatively rare condition, we should consider it in the differential diagnosis of female pseudohermaphrodism.

Clitoris↗

Cryopreserved autologous nipple-areola complex transfer to the reconstructed breast.

If a patient's nipple-areola complex is available for grafting after mastectomy, it is the best material to use for nipple-areola reconstruction. The authors performed delayed autologous nipple-areola complex transfer to reconstructed breasts in 10 patients (mean age, 47 years; range, 40 to 53 years). The nipple-areola complex was cryopreserved with a programmed freezer after mastectomy. Histological examination of the tissue surrounding the nipple and areola eliminated the possibility of cancer invasion. At the time of transfer, the cryopreserved nipple-areola complex was thawed in 37 degrees C water and grafted on a projection made by a denuded dermal flap on the reconstructed breast. Each patient underwent immediate breast reconstruction using an innervated pedicled transverse rectus abdominis musculocutaneous (TRAM) flap. The patients' postoperative courses were uneventful. The timing of transfer ranged from 3 months to 1 year (mean, 5.8 months) after breast reconstruction. Nipple projection was made by the "four" dermal flap in five cases, a round dermal flap in three cases, a double dermal flap in one case, and a denuded skate flap in one case. The follow-up period ranged from 5 to 36 months (mean, 21.8 months). All grafts were adapted. The final evaluation of nipple-areola complex adaptation was good in four cases, fair in four cases, and poor in two cases. Histological examination of the hematoxylin and eosin stains showed no remarkable destruction of the skin of the nipple and areola, and electron microscopic examination of the areola skin revealed no significant change. However, electron microscopic examination of the nipple skin showed serious damage to skin components, including elongation of the desmosome, widening of the intercellular space at the prickle cell and basal layers, and shrinking of prickle and basal cells. Although further development of the freezing process and cryopreservation technique is needed to prevent depigmentation of the nipple and areola, cryopreserved nipple-areola complex transfer to a reconstructed breast could be an alternative method of nipple-areola reconstruction.

Adult↗

Regional differences in ultrasonic assessment of subcutaneous fat thickness in the abdomen: effects on the TRAM flap.

The authors describe the results of fat thickness patterning of the abdominal sites in 50 patients, all of whom required breast reconstruction with a transverse rectus abdominis musculocutaneous flap. The thickness of the abdominal fat was measured at 12 anatomic locations with an ultrasonic instrument. The highest value of the subcutaneous fat thickness was 29.0+/-10.0 mm at a site 2 cm below the umbilicus at the center of the rectus abdominis muscle. The lowest value of the subcutaneous fat thickness was 17.8+/-7.6 mm at a site 2 cm above the umbilicus on the anterior superior iliac spine. Average subcutaneous fat thickness over the abdomen of 50 patients was 24.0+/-9.4 mm. There were 13 patients (group 1) who had an abdominal fat thickness of more than 30 mm, 19 patients (group 2) with an abdominal fat thickness less than 30 mm and more than 20 mm, and 18 patients (group 3) with an abdominal fat thickness less than 20 mm. Complications occurred in 12 of 50 flaps (24%). Among groups 1, 2, and 3 there was no significant difference (p<0.01) in the overall flap complications (15.4: 36.8: 16.7). In summary, subcutaneous fat thickness showed the higher value at the center of the abdomen and the lower value at the lateral site. Abdominal fat thickness is not a risk factor for necrosis of pedicled transverse rectus abdominis musculocutaneous flaps in patients who are thin, average, or mildly obese. Preoperative examination of the abdominal subcutaneous fat thickness should provide useful information for detailed simulation of a reconstructive operation.

Abdominal Muscles↗

Alteration of the 4-sphingenine scaffolds of ceramides in keratinocyte-specific Arnt-deficient mice affects skin barrier function.

Aryl hydrocarbon receptor nuclear translocator (ARNT), a transcription factor of the Per/AHR/ARNT/Sim family, regulates gene expression in response to environmental stimuli including xenobiotics and hypoxia. To examine its role in the epidermis, the Cre-loxP system was used to disrupt the Arnt gene in a keratinocyte-specific manner. Gene-targeted, newborn mice with almost normal appearance died neonatally of severe dehydration caused by water loss. Histology showed small changes in the architecture of cornified layers, with apparently preserved intercorneocyte lamellar structures responsible for the skin barrier function. In contrast, HPLC/ion-trap mass spectrometry revealed significant alterations in the compositions of ceramides, the major components of the lamellae. The murine epidermal ceramides normally contain 4-sphingenine and 4-hydroxysphinganine. In Arnt-null epidermis, 4-sphingenine was largely replaced by sphinganine and the amounts of ceramides with 4-hydroxysphinganine were greatly decreased, suggesting deficiency of dihydroceramide desaturases that catalyze the formation of both 4-sphingenyl and 4-hydroxysphinganyl moieties. A desaturase isoenzyme, DES-1, prefers desaturation, but DES-2 catalyzes both reactions to a similar extent. Transcript levels of Des-2, but not Des-1, were considerably decreased in cultured keratinocytes from Arnt-null epidermis. These results indicate that proper ceramide compositions through 4-desaturation regulated by ARNT are crucial for maintaining the epidermal barrier function.

Animals↗

A novel FERM domain including guanine nucleotide exchange factor is involved in Rac signaling and regulates neurite remodeling.

The Rho family of small GTPases, key regulators of the actin cytoskeleton in eukaryotic cells from yeast to human, is implicated in the control of neuronal morphology. Guanine nucleotide exchange factors (GEFs) are upstream positive regulators of Rho GTPases and integrate extracellular signaling for appropriate activation of Rho GTPases at specific subcellular regions. Here we describe the identification of a novel Dbl family GEF for Rho GTPases in Homo sapiens and Mus musculus. It contains a tandem Dbl homology-pleckstrin homology domain and FERM domain, characteristic of the plasma membrane proteins linker. This gene, termed FERM domain including RhoGEF (FIR), was abundantly expressed in brain, lung, and testis, as well as embryonic hippocampal and cortical neurons. FIR was found to activate the biochemical pathway specific for Rac1 but not for RhoA or Cdc42. Ectopic expression of FIR in the cortical neurons resulted in significantly shortened neurites and excessive growth cones, presumably mediated by Rac1. These results suggest that FIR may regulate neurite remodeling by mediating the signaling pathways from membrane proteins to Rac.

3T3 Cells↗

Functional reconstruction of maxilla with free latissimus dorsi-scapular osteomusculocutaneous flap.

Restoration of oral and nasal function together with facial appearance is still challenging in maxillary reconstruction. Use of a composite flap transfer merely to fill the defect results in unsatisfactory functional and aesthetic outcomes. The authors present a reconstructive procedure for complex maxillary defects using the latissimus dorsi-scapular rib osteomusculocutaneous flap. Some modifications for the reconstruction of the nasal cavity and the hard palate contributed to excellent postoperative functions. Five cases of extended maxillary defect were reconstructed using a novel procedure between February of 1997 and October of 2000. The hard palate was reconstructed with a vascularized scapular angle. The infraorbital rim was reconstructed with a vascularized rib if it was required. A prop bone graft, replacing the zygomatic buttress, was added between the infraorbital rim and the hard palate. The latissimus dorsi muscle flap, which was supported by a skeletal framework and obliterated the remaining cavities around the bone grafts, was left exposed into the nasal cavity, and an 8-French (no. 10) nasal airway tube was placed as a stent in the nasal meatus for 3 weeks after surgery. A skin graft was applied on the scapular angle to reconstruct the oral side of the hard palate. If required, facial skin defect was repaired with a latissimus dorsi musculocutaneous flap or scapular flap. No major complications at the recipient or the donor sites occurred postoperatively in any of the five cases. In cases in which the eyeballs were preserved, almost normal facial appearance was obtained and an orbital extirpation case showed an acceptable postoperative appearance. All five patients returned to an unrestricted diet and their speech was assessed as normal by a speech test. Nasal breathing through the re-epithelialized meatus was possible in all cases. The reconstructed nasal cavity was maintained for more than 6 months in all cases and for more than 2 years in one early case. Rhinometry demonstrated normal function, and histologic findings of the re-epithelialized mucosa over the muscle flap in the nasal cavity revealed a nearly normal architecture. This technique simplifies the reconstructive procedure of massive maxillary defects, including those in the lateral wall of the nasal cavity. It also improves the postoperative oral and nasal functions of the patients.

Adult↗

Management of flaps with compromised venous outflow in head and neck microsurgical reconstruction.

Microvascular tissue transfer has become an indispensable procedure for head and neck reconstruction. Although remarkable progress has been made technically, anastomosed vessel occlusion is still a serious complication. Even with technically skilled microsurgeons, anastomosed vessel occlusion occurs because the technique is not the sole prophylaxis against thrombosis in microsurgery. Therefore, to minimize the possibility of an unfavorable result in microsurgery, microsurgeons must be familiar with management options for a vascular compromised flap. Most investigators have agreed that venous obstruction occurs more often than arterial obstruction. Here, we reviewed the published literature on the salvage of venous compromised flaps from the viewpoints of surgical correction, including reanastomosis and catheter thrombectomy, and nonsurgical procedures, such as a medicinal leech, hyperbaric oxygen, and thrombolytic therapy.

Anastomosis, Surgical↗

Embolization of high flow arteriovenous malformations: experience with use of superabsorbent polymer microspheres.

PURPOSE: To determine efficacy, safety, and requirements for adjunctive embolization or surgery in the treatment of symptomatic arteriovenous malformations (AVMs) with superabsorbent polymer microsphere (SAP-MS) particles. MATERIALS AND METHODS: SAP-MS particles (sodium acrylate and vinyl alcohol copolymer) are nonbiodegradable spheres with a precisely calibrated diameter. SAP-MS particles swell by absorbing fluids and become soft and deformable. Twenty-five patients (16 men, nine women; mean age, 32 y; range 12-66 y) with symptomatic facial (n = 5), upper- (n = 8) and lower- (n = 12) extremity AVMs were treated primarily (n = 23) or preoperatively (n = 2) by transarterial embolization (TAE) treatment with use of SAP-MS particles. Direct puncture embolization (DPE; n = 4) and/or surgical intervention (n = 5; ie, skin graft, resection, or amputation) were required. Surgical specimens from the resected (n = 2) and the amputated (n = 2) patients were evaluated histologically. Follow-up study, including clinical findings and imaging studies, was performed at intervals ranging from 3 months to 1 year. Clinical outcome was evaluated retrospectively, depending on the subjective improvement of symptoms and signs, according to the medical records. RESULTS: Seventy-two TAEs (range, 1-11; mean, 2.8) and 12 DPEs (range, 1-3; mean, 2.4) were performed during the mean follow-up period of 38 months (range, 7-110 mo). Twenty patients (80%) experienced symptom improvement by embolotherapy alone (n = 17) or in combination with surgery (n = 3). One lip and two finger AVMs were totally removed by surgical excision or amputation after TAE treatment. In diffuse upper- (n = 1) and lower- (n = 1) extremity AVMs, the symptoms were uncontrolled. No nerve injury or skin necrosis was observed after TAE treatment with SAP-MS particles. Mucosal necrosis was induced by DPE with ethanol in one patient. Histologically, SAP-MS particles penetrated intralesional vessels and conformed to the vessel lumen, resulting in tight vessel occlusion. Minimal perivascular reaction was observed. CONCLUSION: SAP-MS particles were used safely in TAE treatment of AVM. TAE treatment with use of SAP-MS particles was suitable for certain symptomatic AVMs, but diffuse AVMs remain a challenge and a combination of alternative methods will be necessary for further strategy.

Acrylic Resins↗

Analysis of genes induced in peripheral nerve after axotomy using cDNA microarrays.

One of the most striking features of neurons in the mature peripheral nervous system is their ability to survive and to regenerate their axons following axonal injury. To perform a comprehensive survey of the molecular mechanisms that underlie peripheral nerve regeneration, we analyzed a cDNA library derived from the distal stumps of post-injured sciatic nerve which was enriched in non-myelinating Schwann cells using cDNA microarrays. The number of up- and down-regulated genes in the transected sciatic nerve was 370 and 157, respectively, of the 9596 spotted genes. In the up-regulated group, the number of known genes was 216 and the number of expressed sequence tag (EST) sequences was 154. In the down-regulated group, the number of known genes was 103 and that of EST sequences was 54. We obtained several genes that were previously reported to be involved in regeneration of the injured neurons, such as cathepsin D, ninjurin 1, tenascin C, and co-receptor for glial cell line-derived neurotrophic factor family of trophic factors. In addition to unknown genes, there seemed to be a lot of annotated genes whose role in nerve regeneration remains unknown.

Animals↗

Gastrin-releasing peptide, a bombesin-like neuropeptide, promotes cutaneous wound healing.

BACKGROUND: Little is known about the effects of neuropeptides on wound healing. OBJECTIVE: To investigate the effect of gastrin-releasing peptide (GRP), one of the bombesin-like neuropeptides, on wound healing. METHODS: The effects of GRP on cultured keratinocyte proliferation and migration were measured by BrdU uptake and in vitro scratch assay, respectively. Various concentrations of GRP ointments (0, 10(-9), 10(-8), 10(-7), 10(-6) M) were topically applied to 1.0 mm wounds on porcine flanks. RESULTS: GRP stimulated keratinocyte growth and locomotion in a dose-dependent manner. Topical administration of GRP accelerated macroscopic epidermal regeneration in a dose-dependent manner, as measured by planimetry. Histologic studies also showed that GRP promoted reepithelialization, including epidermal thickness as well as superficial skin coverage. CONCLUSION: Topical use of GRP may clinically accelerate wound healing of burns, injuries, chronic ulcers, and skin graft donor sites through the enhancement of keratinocyte growth and spreading.

Animals↗

Internal jugular vein occlusion in head and neck microsurgical reconstruction.

The internal jugular vein has been the preferred recipient vein in head and neck microsurgical reconstruction. However, recent reports have demonstrated internal jugular vein occlusion after functional neck dissection. The purpose of this article is to demonstrate and discuss the possibility of recipient internal jugular vein occlusion after free tissue transfer. Of 58 patients who received an end-to-side venous anastomosis with the internal jugular vein, four cases of recipient internal jugular vein occlusion were detected during the early postoperative period. Although the success rate of end-to-side anastomosis with the internal jugular vein may be high, microsurgeons should be aware of the possibility of internal jugular vein occlusion.

Aged↗