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Biomedical subjects

K Harii

Publications and source records attributed to K Harii.

At least 19 recordsLinked to original sources

Efficacy of a skin-protection powder for use as a dressing for intractable ulcers.

OBJECTIVE: Stomahesive skin-protection powder has been reported to be useful as a skin-care and skin-barrier product for the management of stomas. This study aimed to evaluate its efficacy, in terms of wound healing, moisture retention and pain management, as an alternative to conventional dressing materials. Both clinical and animal studies were undertaken. METHOD: The efficacy of the Stomahesive powder was tested by measuring the thickness of granulation tissue formed in a total skin defect in a db/db mouse model. We then compared the healing process using either the skin-protection powder or a conventional film dressing material. In the clinical study 17 patients with various intractable ulcers were treated with Stomahesive powder, and healing was evaluated. RESULTS: In the mouse model, granulation tissue in the wounds treated with the powder was 2.86 times thicker than that of the wounds treated with the film dressing. In the clinical study, 16 out of 17 wounds healed completely. CONCLUSION: The Stomahesive powder could be an effective treatment modality for contact ulceration, superficial ulcers with complex contours and morphology, and superficial ulcers contaminated by liquid faeces or vaginal discharge that have not responded to conventional dressings. DECLARATION OF INTEREST: None.

Administration, Cutaneous↗

Correlation between age and the secretions of melanocyte-stimulating cytokines in cultured keratinocytes and fibroblasts.

BACKGROUND: The majority of skin changes associated with ageing are caused by photoageing and reflect cumulative sun exposure. Although the actinic damage plays a major role in skin pigmentation, it is also important to examine the effects of chronological cellular ageing on the pigmentation. The chief cellular components of the skin other than melanocytes are keratinocytes and fibroblasts, and the influences of age-related changes in those cells on skin pigmentation have not been elucidated. OBJECTIVE: To clarify the effects of cellular ageing of keratinocytes and fibroblasts on age-related skin pigmentation. METHODS: Using ELISA analysis, we measured the level of melanogenic cytokines secreted by cultured keratinocytes and fibroblasts derived from skin of various chronological ages. We also compared the cytokine secretion by cultured keratinocytes between the second and fifth cultures. RESULTS: There was no correlation between age and hepatocyte growth factor (HGF), stem cell factor (SCF), and basic fibroblast growth factor (bFGF) secretion by fibroblasts. On the other hand, a significant positive correlation existed between age and interleukin ((IL)-1alpha secretion (R2=0.50, P=0.002), and a relatively weak correlation existed between age and endothelin-1 (ET-1) secretion (R2=0.17, P=0.051, not significant). The IL-1alpha secretion by keratinocytes was significantly increased in the fifth cultures compared with the second cultures (P<0.005). CONCLUSIONS: These findings suggest that IL-1alpha secretion increases as cells grow older, and the increased secretion of IL-1alpha by aged keratinocytes may stimulate HGF production in dermal fibroblasts paracrinely and ET-1 production in keratinocytes autocrinely, which stimulates melanocyte proliferation and induces an increase of tyrosinase activity in melanocytes. Because IL-1alpha is a primary mediator that responds to inflammation and injury, the transcription of genes involved in skin inflammation may be persistently induced in the aged skin. Thus the increased secretion of IL-1alpha by aged keratinocytes in the aged skin may play a role in the accentuated cutaneous pigmentation and other skin ageing.

Adult↗

The mechanism of epidermal hyperpigmentation in café-au-lait macules of neurofibromatosis type 1 (von Recklinghausen's disease) may be associated with dermal fibroblast-derived stem cell factor and hepatocyte growth factor.

BACKGROUND: The mechanism of the accentuated melanization in café-au-lait macules (CALMs) in patients with neurofibromatosis type 1 (NF1; von Recklinghausen's disease) has not been elucidated. OBJECTIVES: To clarify the mechanism involved in the hyperpigmentation of CALMs in NF1. METHODS: Using enzyme-linked immunosorbent assay (ELISA) and reverse transcriptase-polymerase chain reaction (RT-PCR) analysis of cultured cells, we measured the levels of cytokines produced and secreted by keratinocytes and fibroblasts derived from CALMs (group RC: Recklinghausen CALM) skin, compared with cells derived from the skin of normal individuals (group NN: Normal skin of Normal individuals) and cells derived from non-CALM skin of NF1 patients (group RN: Recklinghausen Non-CALM). RESULTS: ELISA revealed that the secretion of hepatocyte growth factor (HGF) and stem cell factor (SCF) by cultured fibroblasts was significantly elevated in group RC compared with groups RN and NN. In parallel, semiquantitative real-time RT-PCR of HGF and SCF mRNAs demonstrated increased expression of both types of transcripts by cultured fibroblasts in group RC compared with group NN. In contrast, the secretion of endothelin-1 and granulocyte/macrophage colony-stimulating factor by cultured keratinocytes occurred at a similar level among all three groups, RC, RN and NN. CONCLUSIONS: These findings suggest that increased secretion of HGF and SCF by dermal fibroblasts may be associated with the accentuated epidermal melanization observed in CALMs in the skin of NF1 patients.

Adult↗

Schwann cell myelination occurred without basal lamina formation in laminin alpha2 chain-null mutant (dy3K/dy3K) mice.

The laminin alpha2 chain is a major component of basal lamina in both skeletal muscle and the peripheral nervous system. Laminin alpha2 chain deficiency causes merosin-deficient congenital muscular dystrophy, which affects not only skeletal muscles, but also the peripheral and central nervous systems. It has been reported that the formation of basal lamina is required for myelination in the peripheral nervous system. In fact, the spinal root of dystrophic mice (dy/dy mice), whose laminin alpha2 chain expression is greatly reduced, shows lack of basal lamina and clusters of naked axons. To investigate the role of laminin alpha2 chain and basal lamina in vivo, we examined the peripheral nervous system of dy3K/dy3K mice, which are null mutants of laminin alpha2 chain. The results indicate the presence of myelination although Schwann cells lacked basal lamina in the spinal roots of dy3K/dy3K mice, suggesting that basal lamina is not an absolute requirement for myelination in vivo. Immunohistochemically, the expression of laminin alpha4 chain was increased and laminin alpha5 chain was preserved in the endoneurium of the spinal root. Laminin alpha4 and alpha5 chains may play the critical role in myelination instead of laminin alpha2 chain in dy3K/dy3K mice. In addition, the motor conduction velocity of the sciatic nerve was significantly reduced compared with that of wild-type littermate. This reduction in conduction velocity may be due to small axon diameter, thin myelin sheath and the patchy disruption of the basal lamina of the nodes of Ranvier in dy3K/dy3K mice.

Animals↗

Pretreatment with topical all-trans-retinoic acid is beneficial for wound healing in genetically diabetic mice.

OBJECTIVE: Topical pretreatment with aIl-trans-retinoic acid (atRA) is known to improve healing of cutaneous wounds. We tested the effect of atRA on wound healing of genetically diabetic db/db mice. It is known that cutaneous wounds of db/db mice show delayed wound healing due to impaired wound contraction, delayed granulation tissue formation and underexpression of keratinocyte growth factor (KGF). METHODS: 0.1% atRA in 100 mg aqueous gel was applied to the back skin of db/db mice as well as to their normal heterozygous littermates, db/+ mice, for five consecutive days, and 2 days after completion of the atRA treatment, two round excisional wounds were created down the panniculus carnosus with a 6-mm punch biopsy on the back skin of each mouse. RESULTS: After 5 days treatment with 0.1% atRA, significant hypertrophy of the epidermis and dermis, neovascularization, and inflammatory cell invasion were seen in the skin of the db/db mice, but these effects were seen only weakly in db/+ mice. Wounds in atRA-treated db/db mice closed more rapidly than those in vehicle-treated db/db mice. KGF mRNA expression, which is usually significantly lower in db/db mice than in normal mice, in wounds of atRA-treated db/db mice on day 1 of treatment was as strong as in db/+ mice. CONCLUSION: Pretreatment with atRA reversed the impaired wound healing in db/db mice.

Administration, Topical↗

Effects of all-trans retinoic acid on melanogenesis in pigmented skin equivalents and monolayer culture of melanocytes.

The effects of all-trans retinoic acid (RA) on melanogenesis and the mechanism of its action in topical treatment have not been elucidated. The purpose of this study was to determine the effects of RA on melanogenesis in the pigmented skin equivalent as well as in monolayer culture of melanocytes, and to determine whether RA, hydroquinone (HQ), and hydrocortisone (HC) show synergistic depigmenting effects in combined treatments of each other. The suppressing effect of RA on melanogenesis was not observed in pigmented skin equivalents and monolayer culture of murine and human melanocytes, although HQ showed strong inhibition of melanogenesis. The synergistic effects between RA, HQ, and HC were not particularly seen. The results suggested that RA neither has direct inhibitory effects on melanogenesis of melanocytes, nor influences the cell-cell interactions between melanocytes, keratinocytes and fibroblasts, such as paracrine actions with regard to melanin production. The role of RA in bleaching treatments appears to be in other specific actions, such as promotion of keratinocytes proliferation and acceleration of epidermal turnover.

Animals↗

Ectopically localized HNK-1 epitope perturbs migration of the midbrain neural crest cells in Pax6 mutant rat.

Small eye rats, which have a mutation in a gene encoding transcription factor Pax6, exhibit impaired migration of the midbrain neural crest cells, thereby showing severe craniofacial defects. Orthotopic grafting of the midbrain neural crest cells taken from the wild-type into Pax6 mutant embryos has suggested environmental defects along the migratory pathway of the midbrain crest cells. In the present study we found that the HNK-1 carbohydrate epitope was ectopically localized in the frontonasal epithelium of Pax6 mutant embryos. The GlcAT-P gene, encoding an enzyme for the synthesis of the HNK-1 epitope, was also expressed ectopically in the frontonasal epithelium of the mutant. In explant cultures, the migration rate of neural crest cells from the midbrain, but not from the forebrain, was significantly less in HNK-1-coated dishes than in non-coated dishes. These results suggest that the arrested migration of the midbrain crest cells in Pax6 mutant embryos may, at least in part, be due to the inhibitory effect of the HNK-1 epitope ectopically localized in the frontonasal epithelium.

Animals↗

Deep circumflex iliac perforator flap with iliac crest for mandibular reconstruction.

The deep circumflex iliac myocutaneous perforator (DCIP) flap with iliac crest was used to reconstruct oromandibular defects in 10 patients. In seven of the patients a dominant perforator was found preoperatively using a Doppler flowmeter; in five of these seven patients a DCIP flap was successfully transferred. In two of the seven patients the dominant perforators were too narrow: one patient underwent a standard osteocutaneous flap transfer and one patient underwent a second flap transfer. In three patients no dominant perforator was found before or during surgery. The freedom of the DCIP flap from the harvested iliac crest facilitates correct positioning. However, to ensure that the DCIP flap can be safely elevated, the presence of perforators must be confirmed preoperatively. Even when a perforator has been identified, complicated dissection may be necessary. We stress the importance of a thorough knowledge of the anatomy of second flaps and of obtaining informed consent to use them.

Adult↗

Skeletal analysis of craniofacial deformities in brachycephaly: comparison with craniofacial deformities in plagiocephaly.

The deformities of craniofacial bones in brachycephaly (n = 2) and plagiocephaly (n = 2) were compared using three-dimensional skull replicas. In brachycephaly the bilateral deformities of the cranial base were similar to the unilateral deformities on the affected side in plagiocephaly. Shortening of the anterior-middle cranial fossas and expansion of the middle cranial fossas suggest downward and anterior displacement of both temporomandibular (TM) joints resulting in the underdevelopment of the middle-inferior facial bones, though this is less conspicuous in brachycephaly for three reasons. The most important one is that the patients have an imposing facial morphology characterised by high, protruding facial bones, as found on the affected side in plagiocephaly. Secondly, the frontal bones are flattened and positioned posteriorly in the anteroposterior direction, which also helps to mask the underdevelopment of the middle-inferior facial bones. Finally, as bony deformities are symmetrical in brachycephaly, they are not as obvious as they would be if they were unilateral.

Child↗

Tattoo removal by grafting enzymatically separated epidermis.

A novel method of tattoo removal in which the enzymatically separated epidermis of an excised tattoo was grafted in situ was applied to 3 patients. Unlike the conventional skin-grafting procedure, this method resulted in the complete obliteration of the tattoos without donor site scars. In 1990, Hosokawa and colleagues first reported a technique similar to the one described, but the enzymatic process required surgery to be performed over two consecutive days and, thus, it did not become an established procedure. A modification of Hosokawa's method enabled the authors to reduce the enzymatic processing time to an hour using Dispase. The thinning of the tattooed skin using a Paget's-type dermatome before its exposure to an enzymatic solution facilitated the enzyme's infiltration of the basal layer of the epidermis. Hence, the time taken for the epidermis to separate from the tattooed skin was markedly shortened. Although laser removal continues to be the optimal treatment method, skin grafting or other abrasive procedures, including dermabrasion and cryosurgery, are still necessary for those patients who want complete tattoo obliteration over a shorter time frame and at less expense. In these patients the authors recommend that their procedure be offered as an alternative treatment to laser removal.

Adult↗

Optimized 3-D CT scan protocol for longitudinal morphological estimation in craniofacial surgery.

Frequent three-dimensional computed tomography scanning may cause deterioration of the lenses of the eye, which are susceptible to x-rays. The authors performed an experimental study using a phantom head to establish an optimized three-dimensional computed tomography scan protocol for longitudinal morphological estimation in craniofacial surgery. Volume computed tomography scans were performed using a Hi-Speed Advantage SG CT scanner (GE Medical Systems, Milwaukee, WI) in the axial plane with a combination of scan parameters of varied values. The radiation doses induced by each scanning were measured using thermoluminescent dosimeter chips attached to the position of the lenses in the phantom. Two-dimensional images in the coronal plane and three-dimensional images of the osseous surface were generated from each accumulated data set. For each scan parameter, the images generated from data accumulated using different values were compared. The study showed that lens radiation dose increased with tube potential and was almost directly proportional to tube current and 1/pitch. The slice thickness did not affect lens radiation doses significantly. Images with good contrast resolution and low artifact level sufficient for estimating morphological changes were obtained using a low tube potential of 100 kVp and a tube current of 100 mA. In regard to z-axis spatial resolution, a slice thickness of less than 3 mm was required for precisely pointing out bony edges in the two-dimensional reformation images. These results led us to conclude that volume computed tomography for longitudinal examination in craniofacial surgery should be kept to a minimum frequency and performed using a low-dose technique, small slice thickness, and large pitch.

Artifacts↗

Mandibular reconstruction using microvascular free flaps: a statistical analysis of 178 cases.

For this article, 178 consecutive cases of mandibular reconstruction using microvascular free flaps and performed from 1979 to 1997 were studied. The purpose of this report is to compare flap success rates, complications, and aesthetic and functional results. The ages of the 131 men and 47 women ranged from 13 to 85 years, with an average of 55 years. Donor sites included the rib (11 cases), radius (one case), ilium (36 cases), scapula (51 cases), fibula (34 cases), and soft-tissue flaps with implant (45 cases). Complications included total flap necrosis, partial flap necrosis, major fistula formation, and minor fistula formation. The rate of total flap necrosis involving the ilium and fibula was significantly higher than that of all other materials combined (p < 0.05). The overall rate of implant plate removal, which resulted from the exposure or fracture of the plate, was 35.6 percent (16 of 45 cases). Each mandibular defect was classified by the extent of the bony defect and by the extent of the soft-tissue defect. The extent of the mandibular bony defect was classified according to the HCL method of Jewer et al. The extent of the soft-tissue defect was classified into four groups: none, skin, mucosal, and through-and-through. According to these classifications, functional and aesthetic assessments of deglutition and contour were performed on 115 subjects, and speech was evaluated in 110. To evaluate the postoperative results, points were assigned to each assessment of deglutition, speech, and mandibular contour. Statistical analysis between pairs of bone-defect groups revealed that there was no significant difference in each category. Regarding deglutition, statistical analysis between pairs of soft-tissue-defect groups revealed there were significant differences (p < 0.05) between the none and the mucosal groups and also between the none and the through-and-through groups. Regarding speech, there was a significant difference (p < 0.05) between the none and the through-and-through groups. Regarding contour, there were significant differences (p < 0.01) between the none and the through-and-through groups and between the mucosal and the through-and-through groups. The points given for each function, depending on the reconstruction material, revealed that there was no significant difference between pairs of material groups. From this prospective study, the authors have developed an algorithm for oromandibular reconstruction. When the bony defect is lateral, the ilium, fibula, or scapula should be chosen as the donor site, depending on the extent of the soft-tissue defect. When the bony defect is anterior, the fibula is always the best choice. When the soft-tissue defect is extensive or through-and-through with an anterior bony defect, the fibula should be used with other soft-tissue flaps.

Adolescent↗

Clinical use of amrinone (a selective phosphodiesterase III inhibitor) in reconstructive surgery.

Amrinone is a selective phosphodiesterase III inhibitor that increases cyclic adenosine monophosphate by preventing its breakdown. It is effective in the treatment of congestive heart failure because of its ability to increase myocardial contractility and vascular smooth muscle relaxation. This study was designed to clarify the potential efficacy of amrinone in plastic surgery by clinically assessing its ability to enhance flap blood flow after reconstructive surgery and relieve intraoperative vasospasm. Its effects were compared with those of prostaglandin E1 and lidocaine, which are widely approved agents for improving the hemodynamics of flaps. In the first clinical study, the effects on flap blood flow after flap transfers were investigated. Twenty-six patients underwent reconstructive surgery with vascularized free or pedicled flaps. Blood flow was measured before and 60 minutes after intravenous infusion of lactated Ringer solution (control), amrinone (10 microg/kg/min), or prostaglandin E1 (10 ng/kg/min) using a laser Doppler flowmeter. In the second study, the effects on relief of vasospasm during operation were evaluated. The blood flow of 28 island flaps was measured by laser Doppler flowmetry immediately after flap elevation and 10 minutes after topical application of saline (control), amrinone (5 mg/ml), or lidocaine (10%) to the pedicle in an attempt to resolve the vasospasm. In both clinical studies, the effects of amrinone were statistically no less than those of prostaglandin E1 and lidocaine. The results show that amrinone positively influences the microcirculatory blood flow of transferred flaps and relieves intraoperative vasospasm in clinical cases. The present study suggests that amrinone could be useful for postoperative and intraoperative care in reconstructive surgery.

3',5'-Cyclic-AMP Phosphodiesterases↗

[Microvascular anastomoses in cervical esophageal reconstruction].

Ischemia or hemostasis in the gastric, jejunal, and colonic pedicle after esophagectomy is believed to contribute significantly to postoperative complications. With the advent of microvascular anastomoses, many surgeons have adopted vascular augmentation (supercharge) as a means of avoiding these difficulties. Microsurgical free tissue transfer represented by the free jejunum and forearm flap also plays an important role in esophageal reconstruction. In this paper, the authors introduce the technical points important for successful revascularization including the choice of recipient vessels, setting up of the reconstructive materials, and postoperative monitoring. In cases of gastric pull-up elevated via posterior mediastinum, the left gastroduodenal vessels are anastomosed to the cervical transverse or superior thyroidal vessels. In cases of duodenal or colonic pull-up elevated via the anterosternal route, the vascular pedicles are anastomosed to the internal mammary vessels which are dissected by resecting the costal cartilage. When the free jejunum flap is used, the cervical transverse or superior thyroidal vessels are most frequently used as recipients. Postoperative monitoring of free flaps is performed using Doppler ultrasound or through a small skin incision made above the transferred tissue. Although gastric or colonic pull-up is difficult to monitor, color Doppler sonography permits quantitative analysis of blood flow and may be a useful option.

Anastomosis, Surgical↗

High-intensity static magnetic fields modulate skin microcirculation and temperature in vivo.

We investigated the acute effect of static magnetic fields of up to 8 T on skin blood flow and body temperature in anesthetized rats. These variables were measured prior to, during, and following exposure to a magnetic field in a superconducting magnet with a horizontal bore. The dorsal skin was transversely incised for 1 cm to make a subcutaneous pocket. Probes of a laser Doppler flowmeter and a thermistor were inserted into the pocket and positioned at mid-dorsum to measure skin blood flow and temperature. Another thermistor probe was put into the rectum to monitor rectal temperature. After baseline measurement outside the magnet, the rat was inserted into the bore for 20 min so that mid-dorsum was exactly positioned at the center, where the magnetic field was nearly homogeneous. Post-exposure changes were then recorded for 20 min outside the bore. Sham-exposed animals were submitted to exactly the same conditions, except that the superconducting magnet was not energized. Skin blood flow and temperature decreased significantly during magnetic field exposure and recovered after removal of the animal from the magnet. The rectal temperature showed a tendency to decrease while the animal was in the magnet. The microcirculatory and thermal reactions in the present study were consistent and agreed with some of the predictions based on mathematical simulations and model experiments.

Animals↗

Topical application of amrinone (a selective phosphodiesterase III inhibitor) for relief of vasospasm.

BACKGROUND: Amrinone, a selective phosphodiesterase III inhibitor, is an agent that possesses a combination of positive inotropic and vasodilating properties as a result of preventing the degradation of cAMP, and it has recently been licensed for the treatment of heart failure. The aim of this study was to investigate the potential therapeutic application of amrinone to resolve vasospasm, which is the major problem in reconstructive surgery. In this study its effect was compared with that of lidocaine, the most commonly used topical vasodilating agent clinically. MATERIALS AND METHODS: The probe of an ultrasonic transit-time volume flowmeter was applied to the femoral artery of rats to measure blood flow. After a baseline recording was obtained, 0.03 ml of epinephrine was applied topically to induce vasospasm. The vessels were then immersed in 1 ml of amrinone (5 mg/ml), 10% lidocaine hydrochloride, or normal physiological saline solution for 1 min in an attempt to resolve the spasm. In another group of animals, no solution was used following administration of epinephrine to allow observation of spontaneous resolution of the vasospasm over time. RESULTS: The results showed an essentially immediate spasm-resolving effect in both the amrinone group and the lidocaine group. The amrinone group showed a significantly greater degree of maximum increase in blood flow than the lidocaine group. The effect of lidocaine decreased with time, whereas amrinone had a more lasting effect. CONCLUSIONS: The findings suggest that amrinone could be used as an effective topical vasodilating agent to resolve vasospasm in reconstructive surgery.

Administration, Topical↗

Differential expression of two glucuronyltransferases synthesizing HNK-1 carbohydrate epitope in the sublineages of the rat myogenic progenitors.

HNK-1 epitope is a cell-surface carbohydrate mediating various cell-cell or cell-substrate interactions. We found HNK-1 epitope in longitudinally arrayed fibers in the subpopulation of the epaxial myotome, and hypaxial myoblasts migrating into the limb bud in the rat embryo. We next investigated the expression patterns of genes encoding two glucuronyltransferases (GlcAT-P, GlcAT-D) and sulfotransferase (Sul-T), which are required for biosynthesis of HNK-1 epitope. GlcAT-P gene was expressed in the non-migrating longitudinal fibers, whereas GlcAT-D gene was expressed in the migrating myoblasts in the limb bud. Sul-T gene expression was ubiquitously observed in all these myogenic populations. Thus, differential expression of GlcAT genes may relate to the epaxial/hypaxial or migrating/non-migrating myoblast lineages.

Animals↗

Identification of myelinated motor and sensory axons in a regenerating mixed nerve.

The common peroneal nerves of Wistar rats were transected and repaired to compare the sequential changes in the numbers of regenerating motor and sensory myelinated axons in a single mixed nerve. At sequential intervals (2, 4, and 12 weeks) after nerve repair, 3 kinds of staining were performed: cholinesterase staining (Karnovsky's staining) for motor axons, carbonic anhydrase staining for sensory axons, and antineurofilament immunohistochemical staining for all axons. At 2 weeks there was a large number of carbonic anhydrase-positive axons (600 +/- 98; mean +/- SD) and cholinesterase-positive axons were occasionally seen. Subsequently, there was a striking increase of cholinesterase-positive myelinated axons, reaching to 302 +/- 50 at 12 weeks. The results suggest that the myelinated sensory axons regenerate faster in the early stage of nerve regeneration and that regeneration of the myelinated motor axons is prominent in the subsequent stage. (J Hand Surg 2000; 25A:104-111.

Acetylcholinesterase↗