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T Horikoshi

Publications and source records attributed to T Horikoshi.

At least 19 recordsLinked to original sources
PubMed2006

Acceleration of de novo cholesterol synthesis in the epidermis influences desquamation of the stratum corneum in aged mice.

Cholesterol, a component of intercellular lipids, is important for stratum corneum (SC) homeostasis, including its barrier function and desquamation. However, cholesterologenesis in the epidermis decreases under basal conditions with aging. We found that the number of horny layers in murine SC increased with the decrease of desquamation in the outermost corneocytes associated with aging. The cholesterol content decreased and the cholesterol sulfate content increased in the horny layer with aging, which resulted in an increase in the ratio of cholesterol sulfate to cholesterol. Moreover, we investigated the effects of accelerated cholesterologenesis on desquamation in aged murine skin following topical application of mevalonic acid. The ratio of cholesterol sulfate to cholesterol in aged murine SC significantly decreased following topical treatment with mevalonic acid, which resulted from an increase in cholesterol content via the acceleration of cholesterologenesis. Treatment with mevalonic acid also significantly reduced the number of cell layers in the SC along with the acceleration of desquamation, as measured by desmoglein I content, corneocyte surface area and proteinase activity. These results indicate that an improvement in the ratio of cholesterol sulfate to cholesterol content by de novo cholesterologenesis may be important for desquamation of the SC in aged epidermis.

Aging↗
PubMed2006

Tracer clearance in radionuclide cisternography in patients with spontaneous intracranial hypotension.

We semiquantitatively analysed radionuclide cisternography in three patients with spontaneous cerebrospinal fluid (CSF) leakage diagnosed by typical symptoms and magnetic resonance imaging findings before and several months after treatment with epidural blood patch. Radioactivity in the whole CSF space was measured immediately after and at 1, 5, 7 and 24 h after intrathecal injection of (111)In-diethylenetriaminepentaacetic acid (DTPA). Initial findings included the vague appearance of leakage in the thoracic spine in two patients, early bladder filling at 1 h in one and a lack of tracer filling into the high cranial convexity in all three. The radioactivity count rapidly decreased within several hours after injection and reached 20% of the initial value at 24 h. In contrast, no rapid decrease was observed after treatment and more than 50% of tracer remained at 24 h after injection. Semiquantitative analysis of tracer clearance may provide additional information in the diagnosis of CSF leakage, especially with no obvious qualitative findings.

Female↗
PubMed2005

Intramedullary spinal cord germinoma expresses the protooncogene c-kit.

A 33-year-old woman first noticed numbness in the both lower extremities and the numbness gradually extended up to the thorax. Magnetic resonance (MR) imaging demonstrated a mass with moderate and heterogeneous enhancement and peritumoural intramedullary cysts in the spinal cord at the T-1 to T-3 levels. The tumour was explored partially and intra-operative pathological examination demonstrated the so-called "two-cell pattern" typical of germinoma. The margin of the tumour was not clear. Histological examination showed germinoma with strong c-kit protein expression on the tumour cell surface. Chemotherapy and radiation therapy were given following surgery. Her neurological deficits were improved but not resolved.

Adult↗
PubMed2005

Effects of glycolic acid on desquamation-regulating proteinases in human stratum corneum.

In order to investigate the mechanism of glycolic acid (GA) function in human stratum corneum, we monitored changes in cathepsin D-like (CD) and chymotrypsin-like (SCCE) proteinases for 3 weeks following topical GA application (50% w/v, pH 0.9) for 30 min to human skin. In the early phase, weakened stratum corneum cohesion in the lower layers was observed on day 2 and the amount of active CD in the upper layer of the stratum corneum was significantly decreased from 30 min until day 2, whereas that in the lower layer remained normal. In contrast, the amount of active SCCE showed no change during the experimental period. The surface pH of the stratum corneum drastically decreased to pH 2 at 30 min and slightly recovered to around pH 3 until 1 day after treatment. From 9 to 19 days, a decrease in corneocyte cell area and a remarkable long-term increase in the amount of active CD in the upper layer were observed. In an in vitro study, the activities of desquamation-regulating proteinases were shown to have remarkably increased at around pH 3, due to activation of CD at its optimal pH. These results suggest that GA functions via at least two different mechanisms, acute activation of CD in the lower layer by acidification around pH 3, along with inactivation of CD in the upper layer, and long-term enhancement of de novo CD production in the few weeks following GA treatment.

Administration, Cutaneous↗
PubMed2004

Suppression of melanogenesis by induction of endogenous intracellular metallothionein in human melanocytes.

Nitric oxide (NO) is a potent intercellular mediator of melanogenesis, whereas metallothionein (MT) is an inducible intracellular antioxidant that has been reported to scavenge NO. We investigated the existence and induction of MT in melanocytes, and its inhibitory effect on NO-induced melanogenesis. The expression of MT was detected in melanocytes, however, at a lower level than in keratinocytes, and its induction was possible by the addition of zinc chloride. Further, an NO-stimulated increase of tyrosinase activity in melanocytes was remarkably suppressed, when MT was induced prior to NO stimulation. Melanogenesis was also suppressed, when dexamethasone was used to induce MT. However, an NO-stimulated increase of tyrosinase expression was not suppressed at the gene and protein level, when MT was induced in melanocytes. The same suppressive effect of melanogenesis was also observed, when alpha-melanocyte-stimulating hormone or endothelin-1 was used as a stimulator. Because these results implied a mechanism other than NO scavenging to explain the suppressive effect of MT induction on melanogenesis, the direct inhibition of tyrosinase by MT was examined. Melanosome fractions were prepared from melanocytes, whose melanogenesis was suppressed by the induction of MT. Tyrosinase suppression was observed in the melanosome fractions, which was neutralized by the addition of anti-MT antibody. These results suggest that MT induction may be effective to suppress melanogenesis stimulated by NO as well as other melanogens, and these suppressive effects might be due to a direct inhibition of tyrosinase activity in melanosome and not a scavenging effect of NO.

Blotting, Northern↗
PubMed2004

Cathepsin D, but not cathepsin E, degrades desmosomes during epidermal desquamation.

BACKGROUND: We previously reported that an ambient aspartic proteinase is crucial to desquamation of the stratum corneum at pH 5. Identification of this aspartic proteinase by using enzyme inhibitors suggested it to be cathepsin D, although we could not exclude cathepsin E. OBJECTIVES: To determine the identity of this aspartic proteinase and its distribution within the stratum corneum. METHODS: We measured enzyme activities of cathepsin D and cathepsin E in the salt and detergent extracts from callus stratum corneum, using a fluorogenic peptide as a substrate and comparing the effect of addition of Ascaris pepsin inhibitor (specific for cathepsin E) with that of pepstatin A (which inhibits both cathepsin D and cathepsin E). Both enzymes were then extracted and purified from plantar stratum corneum samples and identified by Western blotting. Immunofluorescence microscopy was used to investigate the localization of proteinases within human plantar stratum corneum sample sections. RESULTS: We found that 20% of total aspartic proteinase activity could be attributed to cathepsin E, the remainder to cathepsin D. Two subunits of cathepsin D were identified, a mature active form at 33 kDa and an intermediate active form at 48 kDa; cathepsin E was also identified at 48 kDa, although in a stained band 10-fold weaker in the immunoblot. Immunofluorescence microscopy showed the antibody to cathepsin D to be localized in the lipid envelopes of the stratum corneum, whereas that to cathepsin E stained the tissue diffusely. The labelling for cathepsin D was similar to that observed for desmosomes, and immunoelectron microscopy confirmed that cathepsin D was present on desmosomes. On the other hand, cathepsin E occurred intracellularly within the squames. CONCLUSIONS: We conclude that cathepsin D, and not cathepsin E, causes desquamation by degrading desmosomes.

Cathepsin D↗
PubMed2003

Anatomical variations of the ten triangles around the cavernous sinus.

The dimensions of the 10 triangles around the cavernous sinus were measured to define the anatomical characteristics of the triangles and to compare their consistency in shape and area. Twelve tissue blocks containing the bilateral cavernous sinuses and medial two-thirds of the middle cranial fossae were obtained from Japanese adults at autopsy, fixed to a stereotactic frame, and examined with an operative microscope. The dimensions of each triangle were measured with calipers and compared, based on the same point and border. The anteromedial triangle and the superolateral (Parkinson's) triangle were more consistent in shape than the paramedial and oculomotor triangles, but the oculomotor triangle was larger in area than these other triangles. The posteromedial (Kawase's) triangle was more consistent in shape and larger than the anterolateral, lateral, and the posterolateral (Glasscock's) triangles. The anteromedial and superolateral (Parkinson's) triangles are important for the combined epi- and subdural approach to cavernous sinus lesions. The posteromedial (Kawase's) triangle is important for gaining access to the posterior cranial fossa from the middle cranial fossa.

Adult↗
PubMed2003

Coxsackievirus and adenovirus receptor (CAR)-positive immature osteoblasts as targets of adenovirus-mediated gene transfer for fracture healing.

Adenovirus vectors are expected to be a powerful tool for gene therapy to treat severe fractures. Adenovirus invades cells through binding to the coxsackievirus and adenovirus receptor (CAR) on the cell membrane. CAR expression is low in normal adult animals, but it is induced on regenerating cells in some experimental models. We made a rib fracture model in mice and evaluated the histological changes and CAR mRNA expression by RT-PCR 1, 5, 10, 14, and 21 days after the fracture. CAR mRNA was expressed exclusively in the fractured ribs at each time point, but not in the normal ribs. We detected the CAR protein immunohistochemically in fibroblast-like cells in the fracture callus on days 10 and 14 after fracture. In situ hybridization showed that these fibroblast-like cells expressed mRNA of type I collagen and osteopontin, but not osteocalcin, defining the cells as immature osteoblasts. We then transferred small doses (10(4)-10(8) PFU) of lacZ-expressing adenovirus vector into immature osteoblasts on day 14. beta-galactosidase was detected only on the immature osteoblasts at every dose. Immature osteoblasts play an important role in the matrix replacement step in fracture healing. CAR-mediated gene transfer into immature osteoblasts can be reasonable for adenovirus-mediated treatment of fracture healing.

Adenoviridae↗
PubMed2000

Quantification of relative mRNA expression in the rat brain using simple RT-PCR and ethidium bromide staining.

We developed a protocol for quantification of relative gene expression using reverse transcription-polymerase chain reaction (RT-PCR) without the use of radioisotopes, special equipment or extra nucleotide fragments, such as competitors. The relative gene expression of GABA(A) receptor beta(1) subunit (GABA(A)Rbeta(1)) and phospholipase C beta(4) subtype (PLCbeta(4)) in rat cerebrum and cerebellum were determined by comparing the ratio of PCR products generated by linear amplification of the target cDNA segments and glyceraldehyde 3-phosphate dehydrogenase (GAPDH) cDNA segment as a reference. The density of PCR products was measured from digitized images of photographs of ethidium-bromide-stained agarose gels. The linear region of PCR amplification was within the linear range (from 0.3 to 12 ng DNA in a single band) of the detection system. The accuracy of the present method was <2-fold difference in gene expression in a single determination and a 1.5-fold difference was statistically significant after repeated measurements. The estimated relative expression of PLCbeta(4) was significantly higher in cerebellum than cerebrum, and that of GABA(A)Rbeta(1) was the same in these two regions. Using the present method, it is possible to quantify several different subunits and subtypes of known ion channel, neurotransmitter receptor and intracellular signaling enzyme gene families.

Animals↗
PubMed2000

Enhancing effect of electric stimulation on cytotoxicity of anticancer agents against rat and human glioma cells.

Electropermeabilization, or electroporation, has been used to deliver genes or drugs into the cytoplasm through micropores in the cell membrane caused by electric stimulation. The cytotoxic effect of a combination of anticancer agents with electric stimulation on rat C6 and human T98G glioma cells was examined in vitro. Electric pulses of 100 microsec square waves (eight cycles at 1 Hz) at various electric fields were delivered to C6 or T98G glioma cell suspensions in combination with several anticancer agents. Cell growth was evaluated 48-72 h after treatment. Measurement of cell lysis by electric stimulation was used to assess the optimum field strength for electroporation. Electric stimulation enhanced significantly the cytotoxicity of bleomycin to both C6 and T98G cells by more than 1000-fold using an electric field of 1750 V/cm for C6 cells and 1000 V/cm for T98G cells. The enhancement disappeared when bleomycin concentration was reduced to 100 pg/ml. The cytotoxicity of carboplatin was weakly but significantly enhanced by electric stimulation when a high dose of carboplatin was used. However, there was no enhancement of the cytotoxicity of nimustine hydrochloride (ACNU), etoposide, and vincristine. These results indicate that the combination of bleomycin and electroporation is the most potent candidate for electrochemotherapy in vivo.

Animals↗
PubMed2000

Usefulness and pitfalls of intraoperative spinal motor evoked potential recording by direct cortical electrical stimulation.

OBJECTIVE: The aim of this study is to investigate the usefulness and problems with spinal motor evoked potential (MEP) recording, especially the reasons for failed recording. We report our personal experience over the last 8 years in patients with lesions adjacent to the primary motor cortex. METHODS: MEP records of 50 consecutive patients were retrospectively reviewed. MEP was recorded by a catheter electrode inserted in the cervical epidural space. Stimulation electrodes were placed on the cortical surface during surgery. SEP recording was also performed in 29 of 50 patients. RESULTS: MEP was obtained in 40 cases, and SEP was recorded in all 29 cases. The central sulcus was identified in 93% of patients in whom both MEP and SEP were performed, whereas in only 86% of patients who underwent only MEP. The main reason for MEP failure were inadequate exposure of the motor cortex, pre-existing hemiparesis and technical errors. Postoperative deterioration of motor function was closely related to intra-operative MEP changes. CONCLUSION: MEP is a useful tool to determine the motor cortex and to predict postoperative motor function. However, precise pre-operative craniotomy planning and combination with intra-operative SEP is essential to reduce the MEP failure.

Adolescent↗
PubMed2000

Statistical analysis of factors affecting the outcome of patients with ruptured distal anterior cerebral artery aneurysms.

The clinical factors affecting the outcome of patients with ruptured distal anterior cerebral artery (ACA) aneurysms were analyzed using multiple logistic regression analysis. The medical records were reviewed of 52 patients (57 aneurysms) with ruptured distal ACA aneurysms operated on by the same neurosurgeon over 25 years. The standard policy was early surgery for patients in Hunt and Kosnik grades I to IV. Age, sex, Hunt and Kosnik grade, timing of operation, size of aneurysms, number of aneurysms, association of intracerebral haemorrhage (ICH), intraventricular haemorrhage, and azygos ACA, use of temporary clipping, occurrence of premature rupture, and presence of psychiatric change were investigated. Univariant analysis disclosed that clinical grade (P = 0.0006), size of aneurysm (P = 0.005), and size of ICH (P = 0.012) affected the outcome of patients. Multiple logistic regression analysis found that Hunt and Kosnik grade (P = 0.010) and timing of operation (P = 0.033) affected the outcome. There was no significant relationship between long-term outcome and clinical factors, although a close relationship was found with Hunt and Kosnik grade (P = 0.071). Clinical grade and timing of the operation affected the outcome of patients with ruptured distal ACA aneurysms. Patients harboring ICH of over 3 cm diameter in poor grades should also be carefully treated.

Adult↗
PubMed2000

Chronological changes in MRI findings of spinal dural arteriovenous fistula.

BACKGROUND: Intramedullary high-intensity changes on T2-weighted magnetic resonance images (MRI) occur in patients with spinal dural arteriovenous fistulas (AVF). Reduction of the high-intensity area after treatment has been noted; however, there are still questions about whether the change is related to preoperative clinical grade, postoperative improvement, or efficacy of treatment. This study tried to clarify the relationship between chronological changes in the high intensity area with the treatment and clinical course. METHODS: Chronological changes in an intramedullary high-intensity area after surgery were retrospectively analyzed in recent 13 patients with spinal dural AVFs who were treated and followed by MRI. RESULTS: Preoperative intramedullary high-intensity areas were observed on T2-weighted images in all cases. The extent of the high-intensity area correlated with preoperative neurological deficits. The intramedullary high-intensity area was reduced or diminished after successful interruption of AVFs. The high-intensity area started to decrease within 1 to 4 months after treatment in all patients, and disappeared at 2 weeks to 23 months in seven patients. The reduction may suggest interruption of the fistula and improvement of venous circulation, but was not always correlated to clinical improvement. The intramedullary high-intensity areas rapidly disappeared in two patients, but did not clearly correspond to the clinical improvement. CONCLUSIONS: The time course of postoperative MRI changes is helpful for evaluating the efficacy of treatment after surgery for spinal dural AVFs.

Adult↗
PubMed2000

Up-regulation of tyrosinase gene by nitric oxide in human melanocytes.

Ultraviolet light (UV) radiation causes skin-tanning, which is thought to be mediated by stimulating the release of melanogenic factors from keratinocytes as well as other cells. Nitric oxide (NO) has been reported to be generated after UV radiation and to stimulate melanocytes as one of the melanogens. In a previous experiment by another group on melanogenesis induced by NO, increases in both tyrosinase activity and tyrosinase protein levels were observed after daily stimulation of NO for 4 days. In the present study, we investigated tyrosinase gene expression within the first 24 hr of NO-induced melanogenesis. Tyrosinase mRNA expression was found to be induced 2 hr after a single treatment with S-nitroso-N-acetyl-L-arginine. An increase of tyrosinase activity was also detected time-dependently within the 24-hr period, accompanied by an increase of tyrosinase protein levels. The induction of mRNA expression was suppressed by a cyclic guanosine 3',5'-monophosphate (cGMP)-dependent protein kinase (cGMP/PKG) inhibitor. These results suggest that the enhancement of tyrosinase gene expression via the cGMP pathway may be a primary mechanism for NO-induced melanogenesis.

Alkaloids↗
PubMed2000

Involvement of nitric oxide in UVB-induced pigmentation in guinea pig skin.

Ultraviolet (UV) B irradiation evokes erythema and delayed pigmentation in skin, where a variety of toxic and modulating events are known to be involved. Nitric oxide (NO) is generated from L-arginine by NO synthases (NOS). Production of NO is enhanced in response to UVB-stimulation and has an important role in the development of erythema. NO has recently been demonstrated as a melanogen which stimulates melanocytes in vitro, however, no known in vivo data has been reported to support this finding. In this study, we investigated the contribution of NO with UV-induced pigmentation in an animal model using an NOS inhibitor. UVB-induced erythema in guinea pig skin was reduced when an NOS inhibitor, L-NAME (N-nitro-L-arginine methylester hydrochloride), was topically applied to the skin daily, beginning 3 days before UVB-irradiation. Delayed pigmentation and an increased number of DOPA-positive melanocytes in the skin were markedly suppressed by sequential daily treatment with L-NAME. Furthermore, melanin content 13 days after UVB-irradiation was significantly lower in skin treated with L-NAME than in the controls. In contrast, D-NAME (N-nitro-D-arginine methylester hydrochloride), an ineffective isomer of L-NAME, demonstrated no effect on these UV-induced skin responses. These results suggest that NO production may contribute to the regulation of UVB-induced pigmentation.

Animals↗
PubMed2000

Application of SEM-modified X-ray microscope to entomology and histology, and effects of X-ray coherence in imaging.

A projection X-ray microscope has been constructed by modifying a scanning electron microscope (HITACHI S-2500CX). Characteristic internal structures and their changes in an aphid, a fly, an ant, a water bear and a beetle are observed first, non-destructively, by X-ray microscope. Stereo-pair X-ray micrographs of Golgi-stained sections of porcine liver show a network of bile canaliculi and stellate cells. The very clear micrographs presented indicate the usefulness of the microscope in studies of entomology and histology. In some micrographs, very thin whiskers or hairs are visible, which suggests that a phase-contrast effect is present in the imaging. X-ray micrographs of an ant hair taken at various distances between the X-ray source and the specimen, D(s), indicate that the image enhancement due to the phase contrast increases with increasing D(s). Degree of the lateral coherence of X-rays of wave length 0.1 nm is theoretically estimated near the hair, with the result that the coherence increases from about zero (almost complete incoherence) at D(s) = 0.1 mm to about unity (almost complete coherence) at D(s) = 6 mm, in agreement with the observation.

Animals↗
PubMed2000

Response of keratinocytes from normal and psoriatic epidermis to interferon-gamma differs in the expression of zinc-alpha(2)-glycoprotein and cathepsin D.

Psoriasis is a T cell-mediated inflammatory disease characterized by hyperproliferation and by aberrant differentiation. We found cathepsin D and zinc-alpha(2)-glycoprotein, two catalytic enzymes associated with apoptosis and desquamation, to be present in the stratum corneum of the normal epidermis but absent from the psoriatic plaque. Psoriasis is characterized by an altered response to interferon-gamma (IFN-gamma), including the induction of apoptosis in normal but not in psoriatic keratinocytes, often with opposite effects on gene expression of suprabasal proteins. We found that IFN-gamma binding and signaling were attenuated in psoriasis: The IFN-gamma receptor, the signal transducer and activator of transcription STAT-1, and the interferon regulatory factor IRF-1 were strongly up-regulated by IFN-gamma in normal keratinocytes, but not in psoriatic ones. IFN-gamma strongly up-regulated the expression of the catalytic enzymes cathepsin D and zinc-alpha(2)-glycoprotein in normal keratinocytes but down-regulated them in psoriatic ones; the reverse was true of the apoptotic suppressor bcl-2. We believe that the aberrant response to IFN-gamma plays a central role in the pathophysiology of psoriasis, particularly the disruption of apoptosis and desquamation.

Cathepsin D↗