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Biomedical subjects

M Tojo

Publications and source records attributed to M Tojo.

At least 19 recordsLinked to original sources
PubMed2003

Expression of the GLI2 oncogene and its isoforms in human basal cell carcinoma.

BACKGROUND: Mutations of the patched (Ptc) gene, a developmental regulator implicated in the signalling pathway via sonic hedgehog (Shh) and smoothened (Smo), play an essential pathogenic role in the development of basal cell carcinomas (BCCs). We previously reported the upregulation of Shh signal transducers, including Ptc, Smo and hedgehog-interacting protein, in BCCs. In vertebrates, specific downstream effectors in the Shh signalling pathway include three zinc-finger transcription factors, Gli1, Gli2 and Gli3. Gli1 possesses only an activation domain, while Gli2 and Gli3 contain both activation and repression domains. It remains unclear which of these transcription factors are responsible for the development of BCCs. OBJECTIVES: To examine the expression pattern of Gli2 mRNA by human BCCs in comparison with those by normal human skin and various skin tumours. METHODS: We performed quantitative reverse transcriptase-polymerase chain reaction analyses with a series of samples from BCCs, other skin tumours and normal skin. RESULTS: We found that Gli2 mRNA expression was enhanced in the BCCs we examined, whereas there was no significant increase in other skin tumours or normal skin. Of four spliced Gli2 isoforms designated Gli2alpha, beta, gamma and delta, the expression of Gli2beta mRNA was increased the most in BCCs. CONCLUSIONS: As Gli2beta is an isoform spliced at the first splicing site containing a repression domain and consists of an intact activation domain, its overexpression may lead to the upregulation of the Shh signalling pathway, thereby inducing BCCs.

Aged↗
PubMed2002

Expression of a sonic hedgehog signal transducer, hedgehog-interacting protein, by human basal cell carcinoma.

BACKGROUND: Aberrant activation of the hedgehog pathway has been identified in various human tumours, including familial and sporadic basal cell carcinomas (BCCs). It has been postulated that binding of sonic hedgehog protein (SHH) to its receptor, patched protein (PTC), releases the inhibitory effect of PTC against smoothened protein (SMO), another protein of the SHH signalling pathway. The positive SMO signalling is not downregulated in BCCs because of the mutational inactivation of PTC. Recently, hedgehog-interacting protein (HIP) was found to bind to SHH directly and attenuate SHH signalling like PTC, while its expression was induced by SHH signals. OBJECTIVES: To examine the expression patterns of HIP, SHH and PTC gene mRNA by human BCCs, in comparison with those by normal human skin and various skin tumours. METHODS: We performed quantitative reverse transcriptase-polymerase chain reaction analyses with a series of samples from BCCs, other skin tumours and normal skin. RESULTS: We found that the mRNA expression of both HIP and PTC genes was enhanced in all samples of BCCs, whereas none of the other skin tumours tested exhibited an increased level of such mRNAs as compared with normal skin. The transcription of the SHH gene, however, was at a baseline level in most BCCs. CONCLUSIONS: These results indicate that both HIP and PTC gene expression are specifically involved in the development of BCCs, and that the production of HIP is linked with the expression of the PTC gene but not the SHH gene.

Aged↗
PubMed2001

No evidence of deregulated patched-hedgehog signaling pathway in trichoblastomas and other tumors arising within nevus sebaceous.

Nevus sebaceous is a congenital malformation of the skin within which a number of neoplasms showing adnexal differentiation may arise. Recently, deletions in the patched gene region were reported in nevus sebaceous and constitutive activation of the patched-hedgehog signaling pathway was implicated in the development of tumors arising within nevus sebaceous. To substantiate further a role of the patched-hedgehog signaling pathway in secondary tumors arising within nevus sebaceous, we examined 11 nevus sebaceous associated with secondary tumors for loss of heterozygosity of the patched gene region by microsatellite polymerase chain reaction and patched mRNA expression by in situ hybridization. Unexpectedly, however, none of the tumors (including eight trichoblastomas) and nevus sebaceous lesions showed loss of heterozygosity at any polymorphic loci close to the patched gene. Further more, none of the nevus sebaceous lesions and secondary tumors gave detectable signals for patched mRNA. In contrast, four of 11 sporadic basal cell carcinomas, that were examined for comparison, showed loss of heterozygosity at the patched gene locus (p <0.05), and moderate to strong signals for patched mRNA was observed in all seven basal cell carcinoma tumors examined (p <0.0001). Additional investigation by reverse transcription-polymerase chain reaction in four basal cell carcinomas and two nevus sebaceous tumors also showed the expression of Gli-1, another target gene in the patched-hedgehog signaling pathway, in all the basal cell carcinomas samples but not in any of the nevus sebaceous tumors examined. The findings in this study do not support the view that the deregulation of the patched-hedgehog signaling pathway is involved in the pathogenesis of nevus sebaceous and associated tumors, and show that, although morphologically similar, trichoblastomas and basal cell carcinomas have a different molecular pathogenesis.

Adult↗
PubMed2000

Central core disease and congenital neuromuscular disease with uniform type 1 fibers in one family.

We report a family in which the father had central core disease and his son had congenital neuromuscular disease with uniform type 1 fibers. This is the first report of such a combination. Although they had no recognized mutation in the ryanodine receptor gene, it is highly likely that the son also had central core disease but without core structures. The absence of cores may be due to the muscle sample or the young age of the patient since core structures have been reported to increase with age. Although the prevalence of core structures in individual muscles is unknown, there is a possibility of sampling error. In some patients, congenital neuromuscular disease with uniform type 1 fibers is closely related to or identical with central core disease.

Adult↗
PubMed2000

The effectiveness of terazosin, an alpha1-blocker, on bladder neck obstruction as assessed by urodynamic hydraulic energy.

OBJECTIVE: To investigate the effectiveness of terazosin, an alpha1-adrenoceptor blocking agent, on bladder neck obstruction (BNO), by assessing the urodynamic hydraulic energy profile. Patients, subjects and methods The study included 17 men (mean age 60.1 years, range 24-84), comprising 11 patients with BNO (mean age 66.5 years) and six normal volunteers (mean age 48.1 years). A five-transducer microtip catheter was used to measure the pressure in the bladder and at the bladder neck, and in the membranous and bulbous urethra during voiding. All the subjects then received terazosin, 1 mg/day orally for 2 weeks, and were re-assessed. RESULTS: The bladder neck diameter at maximum flow significantly (P < 0.02) increased in the 11 patients with BNO after treatment with terazosin. The relative hydraulic energy profiles before terazosin treatment showed the greatest hydraulic energy loss between the membranous and the bulbous urethra in the normal subjects, and between the bladder neck and the membranous urethra in the men with BNO. After terazosin treatment, the greatest energy loss was between the membranous and the bulbous urethra in men with BNO, similar to that in the normal controls, i.e. the whole profile of relative hydraulic energy became normal. CONCLUSION: Terazosin was effective in opening the bladder neck and improving the hydraulic energy profile in men with BNO.

Adrenergic alpha-Antagonists↗
PubMed2000

[A case of riboflavin-responsive multiple acyl-CoA dehydrogenase deficiency (glutaric aciduria type II)].

We reported a male infant with multiple acyl CoA dehydrogenase deficiency, probably due to electron transfer flavoprotein dehydrogenase deficiency. He was noted to have severe muscle weakness, a high serum creatine kinase (CK) level up to 6920 IU/L, lipid storage myopathy and fatty liver at 6 months of age. A GC/MS analysis of urinary organic acids showed excess excretion of dicarboxylic acids, including glutaric, 2-hydroxyglutaric, adipic, suberic, sebacic, malonic, ethylmalonic and methylsuccinic acids. On a urinary acylglycine analysis, hexanoylglycine and suberylglycine were increased, but not isovalerylglycine, in amount. No ketosis was noted. The muscle pathology showed increased oil-red O positive lipid droplets of various sizes indicative of lipid storage myopathy. There was diffuse decrease in the activity of cytochrome c oxidase. No ragged-red fibers were noted. His clinical symptoms improved remarkably after the administration of riboflavin (100 mg/day) and L-carnitine (1000 mg/day). He was then diagnosed as having probable riboflavin-responsive multiple acyl-CoA dehydrogenase deficiency. The glutaryl CoA dehydrogenase activity in lymphocytes was normal, as were the alpha- and beta-subunits of electron transfer flavoprotein. These findings led us to suspect electron transfer flavoprotein dehydrogenation deficiency. Although he had several episodes of short-term deterioration in clinical and laboratory findings, he developed normally with normal intelligent till 10 years of age.

Acyl-CoA Dehydrogenases↗
PubMed1999

Identification of a novel gene, OASIS, which encodes for a putative CREB/ATF family transcription factor in the long-term cultured astrocytes and gliotic tissue.

Gliosis is a characteristic response of astrocytes to inflammation and trauma of the central nervous system (CNS). To study the mechanisms underlying gliosis, we performed differential display screening for genes specifically induced in long-term cultured astrocytes used as an in vitro gliosis model. We identified and characterized a gene (named OASIS, for old astrocyte specifically-induced substance) expressed in long-term cultured mouse astrocytes, or 'old astrocytes (OA)'. The OASIS gene encoded a putative transcription factor belonging to the cyclic AMP responsive element binding protein/activating transcription factor (CREB/ATF) gene family, with homology to box B-binding factor-2 (BBF-2), a Drosophila transcription factor. Its expression was developmentally regulated; OASIS mRNA was primarily expressed in the salivary gland and cartilage in the mouse embryo and it was transiently upregulated in the brain during postnatal two weeks. The expression became weaker in the adult brain. We also demonstrated that an expression of the OASIS mRNA was induced in response to the cryo-injury of the mouse cerebral cortex. The distribution pattern of the OASIS-positive cells in the injured cortex was very similar to that of the glial fibrillary acidic protein (GFAP)-positive cells. These results suggest that OASIS protein may play a role in gliotic events.

Activating Transcription Factors↗
PubMed1999

Eos: a novel member of the Ikaros gene family expressed predominantly in the developing nervous system.

We identified a novel member of the Ikaros gene family, which has critical roles in the development of lymphoid lineages. This gene, which we named Eos, was expressed predominantly in the developing central and peripheral nervous system. Eos protein could interact with itself and Ikaros protein through its C-terminal portion in the yeast two hybrid assay. These findings suggested that Eos may have important roles in neural development similarly to the Ikaros family in the development of hemolymphoid tissue.

Amino Acid Sequence↗
PubMed1999

Localization of huntingtin-interacting protein-2 (Hip-2) mRNA in the developing mouse brain.

Huntingtin-interacting protein-2 (Hip-2) was identified as a human protein specifically associated with huntingtin in vitro, a gene product affected in patients with Huntington disease (HD). It is a ubiquitin-conjugating enzyme identical to the previously characterized bovine E2-25k. We identified the mouse Hip-2 homologue (mHip-2) and examined its distribution patterns in the developing mouse brain in order to gain an insight into the functional significance of the Hip-2 protein in the normal brain as well as in the pathogenesis of HD. As reported with huntingtin, the mHip-2 mRNA expression developed in parallel with neuronal maturation and became distributed widely in the postnatal mouse brain. This spatiotemporal pattern of mHip-2 mRNA expression resembled that of huntingtin. We further demonstrated that mHip-2 mRNA was colocalized with huntingtin-like immunoreactivity in a single neuron. These findings suggested that the Hip-2 interacted with huntingtin in vivo and played an important role in HD pathogenesis.

Amino Acid Sequence↗
PubMed1999

Expression of sonic hedgehog signal transducers, patched and smoothened, in human basal cell carcinoma.

In basal cell nevus syndrome (BCNS) patients, mutations of a gene, patched (ptc), which encodes a putative signal transducer of sonic hedgehog protein (SHH), were found and are thought to be one of the major causes of BCNS. The SHH signaling pathway is an important developmental pathway, and ptc protein (PTC) is a suppressive component serving as a receptor for the secreted SHH. Another transmembrane protein, smoothened (SMO), forms a complex with PTC and regulates this signaling pathway. Recent transgenic studies have strengthened the importance of the SHH signaling system in the etiology of basal cell carcinoma (BCC). In this study, we examined the expression patterns of mRNA for ptc and smo in two different BCC subtypes and normal skin. We found that the expressions of ptc and smo mRNA were enhanced in the tumor nests of the nodular BCC, especially at the advancing portions, but were under the detectable level in the superficial BCC cases examined, indicating that ptc and smo mRNA expressions might be associated with BCC tumor progression and divide the BCC histologic types into two subtypes, superficial and nodular types. In addition, no obvious signals for ptc and smo mRNA were detected in the normal human epidermis, appendages, or seborrheic keratosis, indicating that the abnormal proliferation of follicular epithelial cells caused by ptc, smo and/or other genetic changes, which also cause ptc and smo overexpressions, might result in BCC tumor formation.

Aged↗
PubMed1999

[Serial cerebral computed tomography and magnetic resonance imaging in a case of hemolytic uremic syndrome with the complication of the central nervous system due to Escherichia coli O157:H7].

We report serial cerebral computed tomography (CT) and magnetic resonance imaging (MRI) in a case of hemolytic uremic syndrome (HUS) with the complication of the central nervous system due to Escherichia coli O157:H7. Although initial brain CT was normal, follow-up CT and MRI revealed lesions in the white matter and bilateral basal ganglia, representing brain edema and infarcts, respectively. Especially, lesions in the bilateral basal ganglia were very unique. Serial CT and MRI findings are useful to understand the mechanism of the complications of the central nervous system associated with HUS.

Brain↗
PubMed1998

Expression pattern of a novel death-promoting gene, DP5, in the developing murine nervous system.

We examined the expression patterns of the DP5 gene, which encodes a protein with apoptosis-inducing activity, in the developing nervous system of mice. This gene was primarily expressed in the spinal motor neurons and peripheral sensory ganglia of mouse embryos and transiently in the postnatal brain, particularly in the entorhinal cortex and hippocampus. These expression patterns suggest that the DP5 gene may be involved in the apoptosis, if not all, of the developing nervous system.

Amino Acid Sequence↗
PubMed1998

[What change was caused under short-time treatment by the Ueda method for severely disabled infants with cerebral palsy? Report of two cases].

A new physical therapy, Ueda method (UM), were performed on two patients with severe motor and intellectual disabilities syndrome and spastic cerebral palsy (CP). The period of the UM therapy was 5 days in one case with spastic CP and 10 days in another case with rigo-spastic CP. They showed the remarkable reduction of abnormal muscle tone and interesting phenomena such as postural changes of extremities and changes of some primitive reflexes. First, peculiar postures of treated extremities appeared on the first day of the UM therapy, associated with the reducing muscle tone of extremities only in the treated side. One case showed immediate change of the posture of treated upper extremity from internal to external rotation of the shoulder joint. Another case disclosed immediate appearance of internal rotation of the hip joint of the treated lower extremity and scissoring posture of legs. These phenomena were transient and disappeared under the UM treatment. Secondly, interesting phenomena in some primitive reflexes were observed after the beginning of the UM therapy. Moro reflex was elicited only in the treated upper extremity, which could not be obtained by stimuli before the UM therapy. After the UM therapy on bilateral arms. Moro reflex appeared bilaterally in two cases. On the other hand, the degree of asymmetrical tonic neck reflex (ATNR) in one case with spastic CP reduced on 5th days under the UM therapy. In another case with rigo-spastic CP automatic walking disappeared on 3rd days after the UM therapy and ATNR appeared. The first phenomena could be due to imbalances of the reduced muscle tones by the UM therapy. Second phenomena could result from the interaction between the nervous systems of Moro reflex, ATNR and automatic walking and the nervous system owing to the abnormal muscle hypertone. Moro reflex might be suppressed by abnormal muscle hypertone. The disappearance of some primitive reflexes might not depend on the maturation of the central nervous system.

Cerebral Palsy↗
PubMed1997

The nature of detrusor bladder neck dyssynergia in non-neurogenic bladder dysfunction.

There have been two major opinions on the pathology or nature of the bladder neck contracture. One is an organic fibrosis, and the other is an accentuated sympathetic nervous function, or detrusor bladder neck dyssynergia. The existence of active detrusor bladder neck dyssynergia in neurogenic bladder was reported in a urodynamical manner using microtip transducer catheters. However, it has not been confirmed whether or not detrusor bladder neck dyssynergia is responsible for bladder neck contracture in patient without neurogenic bladder. The present study was designed to determine by means of video urodynamic study whether or not bladder neck contracture would be of the same nature as detrusor bladder neck dyssynergia in non-neurogenic bladder subjects. The study included 32 male subjects of 16-84 years old (average 52.3): 17 bladder neck contracture subjects including 7 subjects associated with minimum complications (4 with trapped benign prostatic hyperplasia and 3 with incomplete neurological lesion) and 15 non-bladder neck contracture subjects (10 healthy volunteers, 2 chronic prostatitis, 3 prostatodynia). A 5-microtip transducer catheter was used to measure the pressure in the bladder and at the bladder neck, the external urethral sphincter and the bulbous urethra during voiding. Proper localization of the transducers was done with an image intensifier. Bladder outlet obstruction localized at the bladder neck (diameters smaller than 0.75 cm) on voiding cystourethrogram was defined as bladder neck contracture. Detrusor bladder neck dyssynergia was defined where pressures were higher at the level of bladder neck than in the bladder during detrusor contraction. An alpha-blocker, terazosin hydrochloride (0.5 mg, b.i.d., two weeks), was orally administered to subjects judged to have detrusor bladder neck dyssynergia by the above methods for the purpose of confirming whether detrusor bladder neck dyssynergia was really due to accentuated sympathetic nervous function. Detrusor bladder neck dyssynergia was found in seven cases with bladder neck contracture: 6 cases with bladder neck contracture with minimum complications and only 1 case with bladder neck contracture without complications (p < 0.01). Detrusor bladder neck dyssynergia was found at the beginning and ending of micturition, but not at maximum flow. In six cases with detrusor bladder neck dyssynergia, the condition disappeared after terazosin. In conclusion, detrusor bladder neck dyssynergia was not thought to be a major factor of voiding dysfunction in bladder neck contracture in non-neurogenic bladder. In the presence of sympathetic hyperactivity or in cases with increased number of alphareceptors, detrusor bladder neck dyssynergia occurs, being predominantly noted in trapped benign prostatic hyperplasia and neurological disorder patients.

Adolescent↗