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Biomedical subjects

T Moriguchi

Publications and source records attributed to T Moriguchi.

At least 91 records · Page 5Linked to original sources
PubMed1997

Induction of apoptosis by ASK1, a mammalian MAPKKK that activates SAPK/JNK and p38 signaling pathways.

Mitogen-activated protein (MAP) kinase cascades are activated in response to various extracellular stimuli, including growth factors and environmental stresses. A MAP kinase kinase kinase (MAPKKK), termed ASK1, was identified that activated two different subgroups of MAP kinase kinases (MAPKK), SEK1 (or MKK4) and MKK3/MAPKK6 (or MKK6), which in turn activated stress-activated protein kinase (SAPK, also known as JNK; c-Jun amino-terminal kinase) and p38 subgroups of MAP kinases, respectively. Overexpression of ASK1 induced apoptotic cell death, and ASK1 was activated in cells treated with tumor necrosis factor-alpha (TNF-alpha). Moreover, TNF-alpha-induced apoptosis was inhibited by a catalytically inactive form of ASK1. ASK1 may be a key element in the mechanism of stress- and cytokine-induced apoptosis.

Amino Acid Sequence↗
PubMed1997

Allixin, a phytoalexin produced by garlic, and its analogues as novel exogenous substances with neurotrophic activity.

Effects of allixin, a phytoalexin of garlic, and its analogues were studied on the survival and morphology of primary cultured neurons from fetal rat brain. Addition of allixin (1-100 ng/ml) to medium significantly promoted the survival of neurons derived from various regions of brain and increased the number of branching points per axon in hippocampal neurons. Allixin, however, was cytotoxic at higher concentrations (>1 microg/ml). Among the analogues of allixin, 2,6-dimethyl-3-hydroxy-4H-pyran-4-one (DHP) possessed potent neurotrophic activity at concentrations over 10 ng/ml without any obvious cytotoxicity up to 10 microg/ml. DHP also retained the activity to promote axonal branching. These results indicate that DHP is a novel exogenous low molecular weight neurotrophic substance without apparent cytotoxicity. This compound may be a useful prototype leading chemical for developing therapeutic and/or prophylactic drugs for neurodegenerative disorders.

Animals↗
PubMed1997

Comparative analysis on the distribution of heterochromatin in Citrus, Poncirus and Fortunella chromosomes.

Double fluorochrome staining with chromomycin A3 (CMA) and 4'-6-diamidino-2-phenylindole (DAPI) was used to characterize and compare the distribution of constitutive heterochromatin along chromosomes of Citrus, Poncirus and Fortunella species. Only CMA-positive bands were distinguishable in metaphase chromosomes. Preferential distribution of heterochromatin in terminal regions, mainly of the long arm, and centromeric regions of a few long chromosomes was a common feature of these genera. Heteromorphism between possible homologous chromosomes was present in the majority of species. Citrus and Poncirus revealed some remarkably uniform chromosomes without any intensively fluorescing region, whereas Fortunella cultivars were differentiated by the presence of CMA bands in all chromosomes. Through measurements assisted by a computer, amounts of CMA-positive regions were shown to be highest in Fortunella. Similarities between Citrus and Poncirus suggest little heterochromatin diversification among karyotypes of these genera, whereas Fortunella, with higher amounts and more homogenous distribution of heterochromatin, is more divergent.

Chromomycin A3↗
PubMed1997

Neurotrophic activity of organosulfur compounds having a thioallyl group on cultured rat hippocampal neurons.

Several organosulfur compounds found in garlic extract promoted the survival of rat hippocampal neurons in vitro. From the analysis of structure-activity relationship, thioallyl group in these compounds is essential for the manifestation of neurotrophic activity. S-Allyl-L-cysteine (SAC), one of the organosulfur compounds having thioallyl group in garlic extract, also promoted the axonal branching of cultured neurons. These results suggest that thioallyl compounds make a unique group of neurotrophic factors.

Animals↗
PubMed1997

Three-dimensional combined flaps for reconstruction of complex facial defects following cancer ablation.

Instead of conventional multiple-paddle or folded free flaps, the authors introduce three types of free combined tissue transfers for cosmetic and functional restoration of massively large facial defects. Three cases reported here were repaired with combined flaps consisting of two or more tissues, such as combined free anterolateral thigh flaps and vascularized muscle or bone grafts. In cases with complex defects in the upper lateral face, facial dynamics were also reconstructed with a free vascularized innervated muscle graft. A complex hemifacial defect involving the orbita and nose can be easily reconstructed with free osteocutaneous flaps in two stages. For complex craniofacial defects, the concept of combined chimeric tissue transfers is most suitable. The ideal pedicle vessels for the combined flaps are considered to be those in the lateral circumflex femoral system, which is far from the head and neck regions, because flap elevation can proceed simultaneously with tumor resection.

Aged↗
PubMed1997

A double-muscle transfer using a divided rectus femoris muscle for facial-paralysis reconstruction.

There are two types of smiling: without exposure of the teeth (usual smile), and with their exposure (square smile). Performance of the former involves use of the major zygomatic muscle, while the latter is created by the major zygomatic and the depressor labii inferior muscles. The function of the depressor labii inferioris muscle cannot be ignored in facial paralysis reconstruction. A double-muscle transfer using a divided rectus femoris muscle for one-stage reconstruction of both the major zygomatic muscle and the depressor labii inferior muscle is described. The patient suffered facial paralysis caused by an extracranial schwannoma originating from the facial nerve. After the tumor was removed, divided rectus femoris muscle segments were transferred to reconstruct the major zygomatic muscle and the depressor labii inferior muscle. After the pedicle vessel of the muscles was anastomosed to the recipient facial vessel, the long motor nerve of the proximal divided muscle was cross-faced and coapted directly to the prepared contralateral buccal branch. The short motor nerve of the distal muscle segment was sutured to the ipsilateral masseteric nerve. The advantages of divided rectus femoris muscle transfers are that (1) independent muscle contraction can be reconstructed; (2) no tongue or trapezius muscle atrophy occurs because the masseteric nerve is used as the motor source of the labial depressor; (3) only one muscle is sacrificed for muscle grafts; and (4) it is a one-stage reconstruction.

Adult↗
PubMed1997

One-stage reconstruction of established facial paralysis using a rectus abdominis muscle transfer.

A free vascularized rectus abdominis muscle graft with a long motor nerve was used for reconstruction of unilateral established facial paralysis in one stage. Regarding the procedure, the pedicle vessels were anastomosed to the recipient vessels in the ipsilateral face, and the motor nerve of the muscle was sutured to the contralateral facial nerve. The advantages of using the rectus abdominis muscle are as follows: (1) the muscle is very thin, not bulky, (2) the muscle can be split easily to reduce the volume, (3) the intercostal nerve is long enough (more than 20 cm) to reach the contralateral facial nerve for suturing, (4) the pedicle vessels are large and long, (5) it is possible to carry out simultaneous operations with two teams, and (6) the donor-site morbidity is minimal. The disadvantages of this method are that complicated surgical dissection is required to obtain a motor nerve and that a postoperative abdominal hernia may occur.

Adolescent↗
PubMed1997

A full-thickness chondrocutaneous flap from the auricular concha for repair of tracheal defects.

A free full-thickness chondrocutaneous flap from the auricular concha for the repair of large tracheal defects was transferred successfully. The flap is based on the superficial temporal vessels (reversed flow) and the posterior auricular vessels. The advantages of this flap for the repair of tracheal defects are (1) its dissection is easy, (2) thin components of the flap provide a wide postoperative airway, (3) the structure of the reconstructed trachea is made firm by the conchal cartilage with vascularization, (4) the highly vascularized cartilage results in less resorption than a free cartilage graft, (5) the donor site can be repaired easily and is concealed by the remnant auricle, and (6) a long arterial pedicle (reversed flow) can be obtained. The disadvantages are (1) there may be temporary postoperative congestion of the flap, (2) postoperative narrowing of the auriculocephalic sulcus may occur, and (3) a short venous pedicle often requires a vein graft.

Adult↗
PubMed1996

Evaluation of glycogen level in human lung carcinoma tissues by an infrared spectroscopic method.

Glycogen levels in the tissue samples obtained from carcinomas and normal sections of human lungs (26 patients) were studied by measuring the infrared band intensity at 1045 cm(-1) due to glycogen. As an internal standard peak, the band at 1545 cm(-1) (amide II) was chosen, and the ratios of these band areas (A1045/A1545) were compared with histological classification and differentiation of tumors. The glycogen level in the carcinoma tissues was significantly higher than that in the normal tissues (P < 0.01, n = 26). Further, the ratio of amounts of glycogen in the carcinomas and in the normal tissues for adenocarcinoma was higher than that for squamous cell carcinoma (P < 0.01). The increased degree of differentiation of the squamous cell carcinomas appeared to be correlated with an increase in the glycogen level. These results suggest that comparison of glycogen levels in the tumor and normal section of human lung may be used as a differentiating parameter for abnormality and histological classification of tumors. The present Fourier transform-infrared spectroscopy (FT-IR) method may become of wide application for studying various tissue samples.

Adenocarcinoma↗
PubMed1996

Purification and identification of a major activator for p38 from osmotically shocked cells. Activation of mitogen-activated protein kinase kinase 6 by osmotic shock, tumor necrosis factor-alpha, and H2O2.

A stress-activated, serine/threonine kinase, p38 (also known as HOG1 or MPK2) belongs to a subgroup of mitogen-activated protein kinase (MAPK) superfamily molecules. An activity to activate p38 (p38 activator activity) as well as p38 activity itself were greatly stimulated by hyperosmolar media in mouse lymphoma L5178Y cells. The activator activity has been purified by sequential chromatography. A 36-kDa polypeptide that was coeluted with the activity in the final chromatography step was identified as MAPK kinase 6 (MAPKK6) by protein microsequencing analysis. Monoclonal and polyclonal antibodies raised against recombinant MAPKK6 recognized specifically the 36-kDa MAPKK6 protein but did not cross-react with MKK3 proteins. The use of these anti-MAPKK6 antibodies revealed that two major peaks of the p38 activator activity in the first chromatography step reside in the activated MAPKK6. Using a genetic screen in yeast, we isolated MKK3b, an alternatively spliced form of MKK3. Like MKK3 and MAPKK6, MKK3b was shown to be a specific activator for p38 and was activated by osmotic shock when expressed in COS7 cells. Immunoblotting analysis revealed that MAPKK6 is expressed highly in HeLa and KB cells and scarcely in PC12 cells, whereas MKK3 and MKK3b are expressed in all cells examined. Immunodepletion of MAPKK6 from the extracts obtained from L5178Y cells and KB cells exposed to hyperosmolar media depleted them of almost all of the p38 activator activity, indicating that MAPKK6 is a major activator for p38 in an osmosensing pathway in these cells. In addition, MAPKK6 was activated strongly by tumor necrosis factor-alpha, H2O2, and okadaic acid and moderately by cycloheximide in KB cells. Thus, there are at least three members of p38 activator, MKK3, MKK3b, and MAPKK6, and MAPKK6 may function as a major activator for p38 when expressed.

Amino Acid Sequence↗
PubMed1996

Ras-dependent and Ras-independent activation pathways for the stress-activated-protein-kinase cascade.

We have previously shown that osmotic stress activates both the mitogen-activated protein kinase (MAPK) cascade and the stress-activated protein kinase (SAPK, also known as JNK) cascade in rat fibroblastic 3Y1 cells and rat PC12 cells. Here, we show that treatment of these cells with sodium arsenite, a chemical compound that mimics the effects of heat shock, or anisomycin, a protein synthesis inhibitor, induces activation of SAPKs potently. These chemical compounds also stimulated the activity of SEK1/MKK4/JNKK, SAPK activator, and the activity of MEKK, SEK1 activator. Expression of a dominant negative mutant of Ras blocked the anisomycin-induced activation of SAPK and SEK1, but did not affect markedly the arsenite-induced or heat shock-induced activation in PC12 cells. The osmotic-stress-induced activation of SAPK was insensitive to the expression of a dominant negative Ras, but was partly sensitive to down-regulation of protein kinase C. These results suggest the existence of Ras-dependent and Ras-independent activation pathways for the SAPK cascade triggered by environmental stresses including chemical stress in PC12 cells. Cell staining with a specific anti-SAPK serum showed that SAPKs were present in both the cytoplasm and the nucleus under normal conditions, and became located mainly in the nucleus after osmotic stress or ultraviolet treatment, suggesting the nuclear translocation of SAPKs.

Animals↗
PubMed1996

A novel kinase cascade mediated by mitogen-activated protein kinase kinase 6 and MKK3.

A cDNA encoding a novel member of the mitogen-activated protein kinase kinase (MAPKK) family, MAPKK6, was isolated and found to encode a protein of 334 amino acids, with a calculated molecular mass of 37 kDa that is 79% identical to MKK3. MAPKK6 was shown to phosphorylate and specifically activate the p38/MPK2 subgroup of the mitogen-activated protein kinase superfamily and could be demonstrated to be phosphorylated and activated in vitro by TAK1, a recently identified MAPKK kinase. MKK3 was also shown to be a good substrate for TAK1 in vitro. Furthermore, when co-expressed with TAK1 in cells in culture, both MAPKK6 and MKK3 were strongly activated. In addition, co-expression of TAK1 and p38/MPK2 in cells resulted in activation of p38/MPK2. These results indicate the existence of a novel kinase cascade consisting of TAK1, MAPKK6/MKK3, and p38/MPK2.

Amino Acid Sequence↗
PubMed1996

Protein S-thiolation and dethiolation during the respiratory burst in human monocytes. A reversible post-translational modification with potential for buffering the effects of oxidant stress.

Stimulation of the respiratory burst in mouse macrophages or human neutrophils results in the formation of disulfide bonds between low m.w. thiols and sulfhydryl groups on specific cytosolic proteins (S-thiolation). S-thiolation is reversible in certain chemical systems. The aim of the present study was to analyze the dynamic nature of this process in human monocytes under physiologic conditions. We report here that the extent of S-thiolation and the rate of respiratory burst stimulated by opsonized zymosan or phorbol diester increased for 10 to 20 min and then declined (dethiolation) in close association. Individual proteins underwent S-thiolation and dethiolation at different rates. H2O--appeared particularly effective in mediating S-thiolation, based on inhibition of S-thiolation by added catalase and accentuation by azide, which inhibits cellular catalase. S-thiolation did not occur in stimulated monocytes from patients with chronic granulomatous disease. The addition of H2O2 to monocytes or lymphocytes induced rapid S-thiolation (1 to 3 min); a subsequent dethiolation returned most of the proteins to baseline by 15 to 30 min. At 0 degrees C and after addition of 1,3-bis-(2-chloroethyl)-1-nitrosourea, there was effective S-thiolation on exposure to H2O2, but dethiolation was inhibited, suggesting a possible role for glutathione (GSH)/thioredoxin reductase systems in this process. GSH was determined to be the most abundant low m.w. thiol bound to S-thiolated proteins, but gamma-glutamylcysteine and cysteine were also bound. The time of maximal reduction in cytosolic GSH during the respiratory burst (10 min) coincided with the time at which protein-bound GSH was highest. S-thiolation-dethiolation represents a reversible post-translational modification that could protect cellular proteins from irreversible oxidative damage.

Blood Proteins↗
PubMed1996

Diamide primes neutrophils for enhanced release of superoxide anion: relationship to S-thiolation of cellular proteins.

Stimulation of the respiratory burst in phagocytes induces the formation of mixed disulfides between sulfhydryl groups of proteins and low-molecular-weight thiols. We hypothesized that this process (S-thiolation) might be involved in turning off the respiratory burst. However, induction of S-thiolation by pretreatment of neutrophils with diamide, a direct thiol oxidizing agent, actually primed the cells for a two- to fivefold increase in total release and fourfold increase in rate of release of 02- on stimulation by f-Met-Leu-Phe. Generation of intracellular oxidants (hydroethidine fluorescence) was increased ninefold. Priming and S-thiolation were apparent at 1 min of incubation and peaked at 5-10 min. Diamide pretreatment also reduced the lag time between addition of phorbol diester and release of 02- by a mean of 23 s (41%). Dithioerythritol, a sulfhydryl-reducing agent, abolished both the S-thiolation and priming mediated by diamide. H202 also induced priming and S-thiolation; and these were eliminated by dithioerythritol. In contrast to the effect of endotoxin, diamide priming did not affect Ca2+ homeostasis of the neutrophils. Diamide did not significantly alter NADPH oxidase activity in a cell-free system. These findings suggest that sulfhydryl groups on one or more proteins play an important role in modulating the respiratory burst.

Blood Proteins↗
PubMed1996

Free vascularized deep peroneal nerve grafts.

An ideal donor site for vascularized nerve grafts should have a constant anatomy, minimal functional loss after the nerve has been sacrificed, and a dependable blood supply parallel to the nerve over a relatively long distance. Creating a pedicle for a free vascularized deep peroneal nerve graft with the anterior tibial vessels seems to be a most suitable method for repairing long nerve gaps of over 20 cm and digital nerve defects with severe finger damage. Applications of this nerve graft to digital nerve losses with severely scarred beds created by avulsion injury, and two-stage reconstruction in some partial brachial plexus palsies (free vascularized nerve graft in the first stage and free vascularized muscle graft in the second stage) are well indicated. Advantages of this technique are: (1) A long nerve graft (up to 25 cm) can be obtained, and anomalies are rare (the nerve is absent in only 4 percent of cases). (2) The caliber of the vascular pedicle is large (approximately equal to 3 mm). (3) The nerve has a sufficient blood supply from the collateral blood vessels. (4) The graft can be easily obtained in the supine position. (5) A monitoring skin flap, based on the inferior lateral peroneal artery, can be attached to the nerve graft. (6) Sensory loss resulting from the sacrifice of the nerve covers a minimal area. (7) A donor scar on the anterior aspect of the lower leg is more acceptable than one on the posterior aspect because of less movement in walking. Disadvantages of this technique are: (1) Sacrifice of the large vessels in the lower leg may result in circulatory complications in the donor foot; to avoid this problem, preoperative angiography is recommended. (2) The donor scar is in an exposed area in female patients. (3) There may be temporary postoperative edema and disability in the donor leg.

Adolescent↗
PubMed1996

Scarpa's adipofascial flap for repair of wide scalp defects.

Scarpa's fascia is a prominent superficial fascial system of the body. It consists of a single membrane between the superficial fatty layer and deep fatty layer, and lies widely in the lower abdominal wall. We describe a case with a wide scalp defect resulting from a resection of a dermatofibrosarcoma, and reconstruction of the defect with Scarpa's adipofascial flap (i.e., a combined paraumbilical perforator-based adipofascial flap-groin adipofascial flap). The primary advantage of Scarpa's adipofascial flap for scalp defects is that (1) the donor site is most acceptable for a free flap with a minimal donor scar and minimal dysfunction; (2) even in cases in which large flaps are used, donor defects can be closed directly without skin grafting; (3) in the obese patient, this flap is preferable because of cosmetic improvement of the abdominal wall; (4) the donor area has so many perforators that an extended adipofascial flap can be obtained with a combination of these perforators; and (5) the flap may be nourished with one of several arteries, such as the superficial or deep inferior epigastric artery, or the superficial or deep circumflex iliac artery. The disadvantages of this flap are that the territory with a single artery may be smaller than a skin flap with the same artery and oversurfacing of the graft results in a poor cosmetic appearance. Scarpa's adipofascial flap is indicated when the defects are in an exposed area, especially in children, young patients, and females, and when this procedure is combined with a skin-expanding method in the secondary repair.

Adipose Tissue↗
PubMed1996

Free medial thigh perforator-based flaps: new definition of the pedicle vessels and versatile application.

The medial thigh flap is a perforator-based flap nourished with septocutaneous or muscle perforators originating from the femoral vessels. To date, 8 patients have been repaired with this flap and extended or connected flaps including this flap: 4 patients with lower leg defects and 4 patients with intraoral and neck defects. The advantages of this flap are (1) several pedicle perforators exist for this flap, which makes possible duplicated vascular anastomoses to establish reliable circulation of the transferred flap; (2) the flap can be extended or connected to other neighboring flaps in the anterior thigh, so that extensively wide defects can be closed in one stage; (3) the great saphenous vein can be simultaneously used as a vein graft or for venous drainage for the flap; (4) the anterior branch of the femoral nerve can be used for sensory potential; and (5) there is minimum morbidity of the donor defect and a large dominant vessel for the leg can be preserved. The suitable indications for this flap are defects after removal of skin cancer in the foot or lower leg and wide defects after resection of head and neck cancer, which can be reconstructed with the flap connected to neighboring skin flaps. The disadvantages of this flap are that it has a small, short vascular pedicle and the bulkiness of the flap's fatty tissue often requires thinning.

Aged↗