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Biomedical subjects

M Nozaki

Publications and source records attributed to M Nozaki.

At least 37 records · Page 2Linked to original sources

Combined use of normal mode and Q-switched ruby lasers in the treatment of congenital melanocytic naevi.

Melanocytic naevi are common and they are often removed for cosmetic purposes. In recent years, both the normal mode ruby laser and the Q-switched ruby laser have been used, either alone or in combination, for the removal of congenital melanocytic naevi. However, their success was restricted to partial lightening and incomplete histological clearance. We report a new approach, with combined use of normal mode and Q-switched ruby lasers, that improves the effectiveness of the laser removal of pigmentation in congenital melanocytic naevi.

Adult↗

p73 is not mutated in meningiomas as determined with a functional yeast assay but p73 expression increases with tumor grade.

The p53 gene is normally wild type in meningiomas. Since all three members of the p53 gene family recognize the same DNA sequence, tumors containing wild type p53 could decrease transactivation of p53 target genes by mutating either p63 or p73. In meningiomas the most likely target is p73, because loss of heterozygosity of the chromosomal band containing p73 is the commonest genetic lesion in these tumors. To screen p73 for mutations we have developed a functional assay which tests the ability of p73 to activate transcription from a p53-responsive promoter in yeast. The assay correctly identified p73 mutants with mutations equivalent to hotspot mutations in p53, demonstrating that the assay can detect transcriptionally inactive p73. No mutations in p73 were identified in meningiomas. p73 RNA level was higher in more advanced tumors, but there was no correlation between the expression level of p73 and p21, a known p53 target gene. The yeast assay was also used to measure the intrinsic sensitivity of the p73 protein to mutagenesis. Like p53, p73 is exceptionally easy to inactivate as a transcription factor by point mutation. Taken together, these results indicate that p53 and p73 serve very different functions in tumors.

Aged↗

Histopathological examination of two cases of anterior staphyloma associated with Peters' anomaly and persistent hyperplastic primary vitreous.

AIMS: To clarify the developmental mechanism and critical period for the uncommon complex of Peters' anomaly and persistent hyperplastic primary vitreous (PHPV). METHODS: Two eyes with Peters' anomaly and PHPV were histologically examined by serial section. One eye was enucleated at age 7 months (case 1) and the other at age 4 months (case 2) owing to severe anterior staphyloma. RESULTS: In both eyes, defects in the endothelium, Descemet's membrane, and posterior stroma were observed in the central cornea, and the degenerative lens adhered to the posterior surface of the defective corneal stroma. Also, in both eyes, the anterior chamber space was not formed and the undifferentiated iris stroma adhered to the posterior surface of the peripheral cornea. Mesenchymal tissue containing melanocytes was observed behind the degenerative lens, and the pigment epithelium was absent at the lower nasal side of the ciliary body in case 1. In case 2, mesenchymal tissue containing scattered melanocytes in the vitreous cavity was seen on the posterior retina. Based on the histological findings, both cases were diagnosed as Peters' anomaly caused by the faulty separation of the lens vesicle, PHPV, maldevelopment of the iris and ciliary body, and goniodysgenesis. CONCLUSION: Migratory disorders of neural crest cells from 4 to 7 weeks of gestation may be responsible for various ocular anomalies including Peters' anomaly and PHPV, as observed in these cases.

Abnormalities, Multiple↗

Preliminary report of a new approach to sparing the greater saphenous vein for grafting: valvuloplasty combined with axial transposition of a competent tributary vein.

PURPOSE: To compare a new vessel-sparing technique combining valvuloplasty with axial transposition of a competent tributary vein versus single valvuloplasty for the treatment of greater saphenous vein (GSV) incompetence. METHODS: In 55 patients with GSV incompetence, 29 of 57 limbs were treated by angioscopic valvuloplasty of the subterminal valve alone, whereas the remaining 28 limbs underwent angioscopic valvuloplasty combined with axial transposition of a competent tributary vein identified preoperatively by duplex scanning. After angioscopic valvuloplasty in the latter group, the competent tributary vein was exposed and cut 1.5 cm distal to its insertion point on the GSV. The transected vein was anastomosed end to side to the GSV, which was ligated between the tributary insertion site and the anastomosis. Changes in venous hemodynamics, including venous filling index (VFI), ejection fraction (EF), and residual volume fraction (RVF), were analyzed by use of air plethysmography. RESULTS: In the 1-year follow-up, no venous thrombosis was detected in either group. In the valvuloplasty-only group, 22 (75.9%) limbs exhibited reflux in the proximal GSV; recurrent varicose veins were detected in 5 (17.2%) limbs. In contrast, only 2 (7.1%) limbs showed reflux in the valvuloplasty + transposition group. There were no significant differences in EF and RVF between the groups before or after the operation, although a significant difference was seen in VFI at 1 year (p = 0.005, Wilcoxon rank sum test). CONCLUSIONS: Valvuloplasty combined with tributary vein transposition gives a better result than valvuloplasty alone at 1 year. This new treatment option may be useful for both reducing the rate of varicose veins and sparing the GSV for grafting.

Adult↗

[Clinical features of epidemic nosocomial keratoconjunctivitis in 41 patients].

PURPOSE: To evaluate the clinical features of nosocomial epidemic keratoconjunctivitis (EKC) occurring in the ophthalmology ward of Tokyo Medical University Hospital. MATERIALS AND METHODS: We studied the symptoms and clinical course of 41 patients who had EKC caused by nosocomial infections in our hospital. We attempted to detect adenovirus antigen and viral DNA from conjunctival swabs and also to isolate the virus. RESULTS: The clinical symptoms of EKC, including postoperative cases, were not severe. In some cases, patients' complaints, for example, increase of lacrimation or appearance of a foreign body sensation, were contributory to diagnosis. Among the 41 patients, 31 out of 34 (91.2%) EKC patients who had undergone ophthalmic surgery had EKC in the operated eye. In cases receiving bilateral operations, EKC occurred first in the initially operated eye. The sensitivity of Adeno-check was 76.9%. Adenovirus type 19 was isolated from conjunctival swabs in 26 cases. CONCLUSIONS: The early diagnosis of EKC is extremely important to prevent the spread of nosocomial infections. Careful observation of operated eyes and close attention to patient complaints may aid in the early detection of EKC.

Adenoviridae Infections↗

[Reconstruction after cervical esophagectomy using a free jejunal graft].

Reconstruction after cervical esophagectomy using a free jejunal graft and forming an additional "vocal canal" are described. It is necessary to pay attention to several points, for example, selection of the jejunal graft, selection of the cervical vessels for anastomosis, technique of hypopharyngeal-jejunal anastomosis, and postoperative management of the anastomotic vessels. These contribute to the improvement of patient quality of life. Forming an additional "vocal canal" in patients who underwent radical surgery is particularly desirable. In this article, we introduce our operative method.

Anastomosis, Surgical↗

Reduced latency but no increased brain tumor penetrance in mice with astrocyte specific expression of a human p53 mutant.

p53-germline mutations located in the core DNA-binding domain have been associated with a more dominant tumor penetrance especially for breast cancer and brain tumors. We previously reported an unusual accumulation of CNS tumors associated with a unique p53 germline mutation, Y236delta (deletion of codon 236). To test whether this tissue-specific tumor predisposition reflects a gain-of-function activity of Y236delta, we generated transgenic mice expressing Y236delta in astrocytes using the regulatory elements of the glial fibrillary acidic protein (GFAP) gene. After transplacental exposure to N-ethyl-N-nitrosourea (25 mg/kg BW) brain tumors developed in 18% (7/39) of GFAP-Y236delta transgenic p53-/- mice, while in p53+/- mice the incidence was 28% (11/40) (P>0.3). However, the mean tumor latency for GFAP-Y236delta/p53+/- mice was significantly shorter than for p53+/- mice, with 19.9 weeks vs 31.6 weeks (P=0.039), respectively. Taken together, cell specific expression of Y236delta results in an acceleration of tumor progression but does not confer a higher tumor penetrance. Conceivably, the transdominant effect of Y236delta provided a growth advantage early in the progression of neoplastic cells, since the endogenous p53 wild-type allele was lost in all brain tumors independent of the genotype. This reflects well observations from human astrocytic neoplasms with p53 mutations.

Animals↗

Cytokeratins 8 and 19 in the mouse placental development.

To investigate the expression and biological roles of cytokeratin 19 (K19) in development and in adult tissues, we inactivated the mouse K19 gene (Krt1-19) by inserting a bacterial beta-galactosidase gene (lacZ) by homologous recombination in embryonic stem cells, and established germ line mutant mice. Both heterozygous and homozygous mutant mice were viable, fertile, and appeared normal. By 7.5-8.0 days post coitum (dpc), heterozygous mutant embryos expressed lacZ in the notochordal plate and hindgut diverticulum, reflecting the fact that the notochord and the gut endoderm are derived from the axial mesoderm-originated cells. In the adult mutant, lacZ was expressed mainly in epithelial tissues. To investigate the possible functional cooperation and synergy between K19 and K8, we then constructed compound homozygous mutants, whose embryos died approximately 10 dpc. The lethality resulted from defects in the placenta where both K19 and K8 are normally expressed. As early as 9. 5 dpc, the compound mutant placenta had an excessive number of giant trophoblasts, but lacked proper labyrinthine trophoblast or spongiotrophoblast development, which apparently caused flooding of the maternal blood into the embryonic placenta. These results indicate that K19 and K8 cooperate in ensuring the normal development of placental tissues.

Animals↗

Detection of PTEN nonsense mutation and psiPTEN expression in central nervous system high-grade astrocytic tumors by a yeast-based stop codon assay.

We have developed a new yeast-based assay for the detection of PTEN nonsense mutation, and applied it to a total of 42 astrocytic tumors. The assay utilizes homologous recombination of PCR-amplified PTEN cDNA samples to a yeast vector which expresses an in-frame PTEN::ADE2 chimera protein. An allele of nonsense mutation in the sample PTEN mRNA gives a truncated chimera protein in a yeast cell, resulting in the formation of a red colony. The assay and subsequent sequence analysis demonstrated nonsense mutations as red colonies of more than 10% in one of 10 anaplastic astrocytomas and six of 18 glioblastomas, but none in six pilocytic astrocytomas or in eight astrocytomas. Sequence analysis of white colonies showed one missense mutation in a glioblastoma. Interestingly, four of seven nonsense mutations were frame-shifts due to exon skipping. In addition, pink colonies were found in one of six pilocytic astrocytomas, three of eight astrocytomas, two of 10 anaplastic astrocytomas, and 10 of 18 glioblastomas. Sequence analysis of the pink colonies revealed a sequence similar to those reported as psiPTEN/PTH2. By testing mRNA and genomic DNA, it was found to be a processed pseudogene which was transcribed. The psiPTEN expression was complementary to PTEN mutation, for 14 of 18 glioblastomas showed either PTEN mutation or psiPTEN expression and only one case showed both PTEN mutation and psiPTEN expression (P<0.046), suggesting a pathological role of psiPTEN expression as an alternative to PTEN mutation in glioblastomas.

Astrocytoma↗

Prostate-specific transcription factor hPSE is translated only in normal prostate epithelial cells.

We recently cloned a novel transcription factor gene, hPSE, which belongs to the Ets gene family. hPSE mRNA was expressed specifically in prostate glandular epithelial cells and also in the human prostate carcinoma cell lines PC-3 and LNCaP. On the other hand, on immunoblot analysis with anti-hPSE antiserum, hPSE protein was detected only in human prostate tissue samples and not in PC-3 or LNCaP culture cells. Immunohistochemistry and in situ hybridization analysis revealed that hPSE protein was translated in normal prostate glandular epithelial cells, but not in carcinoma cells with hPSE transcripts. These findings suggest that expression of hPSE is regulated translationally in prostate epithelial cells and that hPSE protein is a candidate for a marker distinguishing normal cells from cancer cells in the prostate. It appeared that the 5'- and 3'-untranslated regions of hPSE transcripts might be necessary for translational control of hPSE, on the basis of results of transfection analysis in non-prostate lineage cells (HEK-293) using some deletion mutants of hPSE cDNA.

Cell Transformation, Neoplastic↗

Precision measurement of cosmic-Ray antiproton spectrum

The energy spectrum of cosmic-ray antiprotons ( &pmacr;'s) has been measured in the range 0.18-3.56 GeV, based on 458 &pmacr;'s collected by BESS in a recent solar-minimum period. We have detected for the first time a characteristic peak at 2 GeV of &pmacr;'s originating from cosmic-ray interactions with the interstellar gas. The peak spectrum is reproduced by theoretical calculations, implying that the propagation models are basically correct and that different cosmic-ray species undergo a universal propagation. Future BESS data with still higher statistics will allow us to study the solar modulation and the propagation in detail and to search for primary &pmacr; components.

Journal Article↗

Cloning and expression of the mouse Pse gene encoding a novel Ets family member.

Human prostate-specific Ets (hPSE) is a novel Ets transcription factor and is exclusively expressed in human prostate glandular epithelium. To explore the role of PSE, we cloned the mouse Pse (mPse) and examined its pattern of expression. A sequence analysis indicated that mPse contains a conserved carboxy-terminal ETS DNA-binding domain and central Pointed domain, and the overall amino acid sequence shares 86% identity with that of hPSE. The ETS DNA-binding domain is highly conserved between human and mouse (98.8% sequence identity) and is similar to Drosophila dets4 (76.7% identity), but not similar to other Ets factors. A Northern blotting analysis revealed that mPse shows organ-specific expression. An in situ hybridization analysis of the prostate and intestine showed that mPse transcripts were present in their epithelial cells. mPse transactivates the promoter of the MASPIN gene in transient transfection assay. These results suggest that mPse encodes a novel Ets family member and is expressed in epithelial cells of restricted organs.

Amino Acid Sequence↗

The distribution of lamprey GnRH-III in brains of adult sea lampreys (Petromyzon marinus).

In the sea lamprey, Petromyzon marinus, two forms of GnRH, lamprey GnRH-I and -III, have been demonstrated to be neurohormones regulating the pituitary-gonadal axis. The objective of the present study was to determine the distribution of lamprey GnRH-III in the brains of adult sea lampreys and to compare it to the distribution of lamprey GnRH-I. For this purpose, two kinds of immunostaining were employed: one was a single immunostaining by one of two GnRH antibodies using two successive sections; the other was double immunostaining of a single section. A dense accumulation of neuronal cells immunoreactive (ir) to antisera against either lamprey GnRH-I or -III was found in the arc-shaped preoptico-anterior hypothalamic area. Additional smaller numbers of irGnRH cells were found in the periventricular zone of the posterior hypothalamus. In the above-mentioned locations, the distribution of both irGnRH-I and -III cells was intermixed and very similar, but the cells exhibiting GnRH-III immunoreactivity were distinctly different from those exhibiting GnRH-I immunoreactivity. The relative numbers of irGnRH-III cells were larger than those of irGnRH-I cells in the preoptico-anterior hypothalamic area, and more than 90% of GnRH cells in the posterior hypothalamus were irGnRH-III cells. Both irGnRH-I and -III cells projected their fibers primarily into the neurohypophysis. The relative densities of the accumulated irGnRH-III fibers were similar to those of irGnRH-I fibers in the anterior neurohypophysis but higher than those of irGnRH-I fibers in the posterior neurohypophysis. The present study provides further immunocytochemical data to the already compelling physiological evidence that indicates that both lamprey GnRH-I and -III act through the hypothalamic-pituitary-gonadal axis to modulate reproductive processes in the sea lamprey.

Animals↗

Predictive Values in the Progression of Chronic Venous Insufficiency Associated with Superficial Venous Incompetence.

The purpose of this study was to define predictive values in the progression of chronic venous insufficiency in patients with isolated superficial venous incompetence using duplex ultrasound and air plethysmography (APG). Five hundred eight legs in 371 patients with isolated superficial venous incompetence were included in this study. A color duplex scanner with a 5- to 10-MHz linear transducer was used to assess the distribution and the extent of venous reflux as well as the duration of reflux and the retrograde peak velocity at the saphenofemoral junction, greater saphenous vein in the thigh, and the saphenopopliteal junction. Venous reflux was considered to be present if the duration of reflux was greater than 0.5 s. The extent of greater saphenous vein is divided into 3 types. Type I: reflux from the groin to the ankle. Type II: reflux from the groin to the below-knee level. Type III: reflux from the groin to the above-knee level. Values obtained by APG were the venous volume (VV), venous filling index (VFI), ejection fraction (EF), and residual venous fraction (RVF). Between-group differences were analyzed using Wilcoxon's nonparametric rank sum test. Type I limbs had highest incidence of advanced chronic venous symptoms. Based on the duplex-derived duration of reflux and retrograde peak velocity in Type I limbs, there were three major groups: limbs with a retrograde peak velocity greater than 30 cm/s and a duration of reflux less than 3 s (group A), limbs with a retrograde peak velocity greater than 30 cm/s and a duration of reflux greater than 3 s (group B) and limbs with a retrograde peak velocity of less than 30 cm/s and a duration of reflux greater than 3 s (group C). Most of the class 2 and class 3 limbs belonged to Group C, whereas most of the class 4 limbs and all of the class 5 and class 6 limbs belonged to group A and group B. APG-derived VFI had significantly higher values in group A and group B compared with group C (P < 0.002). Peak velocity greater than 30 cm/s had a high positive predictive value of 75.0% with a sensitivity of 91.1%. Although duplex-derived duration of reflux is widely used to assess venous reflux, our data suggest that the peak velocity is a better predictor of the progression of chronic venous insufficiency and that it correlates well with the severity of the clinical manifestation in cases with isolated superficial venous insufficiency.

Journal Article↗

Ocular and systemic features of Peters' anomaly.

BACKGROUND: To clarify the relationship between associated systemic anomalies and ocular manifestations in patients with Peters' anomaly, a retrospective study was conducted. METHODS: We classified 37 patients with Peters' anomaly into two groups, one with (+) and one without (-) systemic anomalies. RESULTS: The systemic anomaly (+) group consisted of 13 patients, eight males and five females, with mean age of 2.3 months. Peters' anomaly was bilateral in six cases and unilateral in seven. Corneolenticular adhesion was observed in 11 cases. Associated ocular anomalies were seen in 12 cases, and developmental glaucoma was present in eight cases. The systemic anomaly (-) group comprised 24 patients, 13 males and 11 females, with mean age of 28.3 months. Peters' anomaly was bilateral in 11 cases and unilateral in 13. Corneolenticular adhesion was observed in five cases. The associated ocular anomalies were observed in 10 cases, and developmental glaucoma was accompanied in six cases. The incidences of cases with corneolenticular adhesion, those with other ocular anomalies, and those with glaucoma were significantly higher in the systemic anomaly (+) group than in the systemic anomaly (-) group. CONCLUSIONS: Peters' anomaly accompanying corneolenticular adhesion and/or other ocular anomalies should be evaluated for the presence of systemic anomalies.

Corneal Opacity↗

Experimental study of an artificial esophagus using a collagen sponge, a latissimus dorsi muscle flap, and split-thickness skin.

The time and effort spent trying to devise an artificial esophagus have not yet resulted in success, and leakage and strictures at the anastomotic sites remain the most frequent complications. We developed an artificial esophagus with a bilayered structure made of porous collagen sponge (artificial dermis; AD), a latissimus dorsi muscle flap (LD), and split-thickness skin (STS). We investigated whether the use of AD prevented the contraction of grafted skin and its effects on the extensibility of the neoesophagus in rabbits. We experimented with two groups. In the AD group, AD was applied to the surface of the LD. Three weeks later, the STS was grafted. In the control group, the STS was grafted directly onto the LD. The sizes of the STS in both groups 3 weeks after the graft were, respectively, 56.6% +/- 4.1% and 39.0% +/- 10.2% of the initial surface area of the STS (P < 0.01). The roll made in the AD group had better extensibility than that in the control group. We replaced the cervical esophagus in 12 rabbits with the neoesophagus made from AD, STS, and LD. The longest survival period was 16 days. Esophagography did not reveal either anastomotic leakage or stenosis in any of the five rabbits in the experiments. These findings suggested that AD can thus be used to create a more suitable hybrid artificial esophagus.

Animals↗

Two N-terminally truncated forms of C-type natriuretic peptide from habu snake venom.

Two N-terminally truncated forms of the C-type natriuretic peptide (CNP) were isolated from the venom of habu snake, Trimeresurus flavoviridis, and their structures were determined by EMI-MS spectrometry and amino acid sequencing. Tf-CNP(6-22), the shorter peptide retaining the 17-membered ring structure formed by an intra-molecular disulfide bridge, has a vasorelaxant activity in rat aortic strips and a diuretic potency in anesthetized rats. Tf-CNP(3-22), the other 20 amino acid residues peptide, also comprised the 17- membered ring with a short N-terminal extension of 3 amino acid residues. Tf-CNP(6-22), the ring, is the shortest naturally occurring CNP peptide identified so far, and as potent as Tf-CNP(1-22), the supposedly intact CNP of 22 amino acid residues.

Amino Acid Sequence↗