Biomedical subjects
Publications and source records attributed to M Nakayama.
We described a rare case of a 20-year-old woman with an ovarian immature teratoma who resumed regular spontaneous menses after more than 5 years of chemotherapy-induced amenorrhoea. Efforts to reverse chemotherapy-induced ovarian failure can be continued even after persistent menstrual dysfunction of 5 or more years.
Brain-derived neurotrophic factor and fibroblast growth factor 2, and their respective binding sites, tyrosine kinase B receptor and fibroblast growth factor receptor 2, are known to regulate neurite outgrowth and antioxidant enzyme activity. Several studies suggest that brain-derived neurotrophic factor and fibroblast growth factor are contained in the inferior colliculus. Previous work in our laboratories revealed dendritic and synaptic losses in the inferior colliculus of aged Fischer-344 rats, along with coincident increases in lipid peroxidation possibly linked to a decrease in activity of antioxidant enzymes. In an effort to identify potential causal mechanisms underlying age-related synaptic and dendritic losses that occur in the inferior colliculus, the present study attempted to determine if inferior colliculus levels of tyrosine kinase B receptor and fibroblast growth factor receptor 2 expression are altered with age. Immunocytochemistry was performed in the inferior colliculus, hippocampus and cerebellum of 3-month-old F344 rats to study distributions of the full-length and truncated isoforms of tyrosine kinase B receptor, and fibroblast growth factor receptor 2. The latter two brain regions served as positive controls. For all three antigens, immunolabeling was localized primarily in somata and proximal dendrites in all subdivisions of the inferior colliculus, and in the dentate gyrus and Ammon's horn of the hippocampus. In the cerebellum, the somata and dendrites of the Purkinje cells were also immunolabeled.A significant reduction in levels of the full-length form of tyrosine kinase B receptor in 18- and 25-month-old rats (respectively, approximately 20% and 30% relative to 3-month-olds) was revealed using western blot analyses. Inferior colliculus and hippocampal levels of the truncated form were modestly decreased ( approximately 7%) as well in the two older age groups. In contrast, levels of fibroblast growth factor receptor 2 in the inferior colliculus and hippocampus were elevated by approximately 35% in the two older age groups when compared to 3-month-olds. Changes in cerebellar levels of tyrosine kinase B receptor and fibroblast growth factor receptor 2, while similar to those in the inferior colliculus and hippocampus among the age groups, did not achieve statistical significance in this study. These findings give rise to the possibility that age-related reductions in tyrosine kinase B receptor levels could be a causal factor in the degenerative changes observed in the inferior colliculus of aged animals, including mitochondrial damage and dendritic regression. The observed increases in fibroblast growth factor receptor 2 levels may be compensatory to the increased oxidative stress. The effectiveness of the fibroblast growth factor receptor 2 response is questionable given the damage that occurs in the inferior colliculus and hippocampus of aged animals. However, the deficits could worsen in the absence of an increase in fibroblast growth factor receptor 2.
PURPOSE: To evaluate the clinical results of phacoemulsification and implantation of 2 foldable acrylic intraocular lenses (IOLs) in microphthalmic eyes. SETTING: University of Tokyo School of Medicine, Tokyo, Eguchi Eye Hospital, Hakodate, and Osaka Rosai Hospital, Osaka, Japan. METHODS: This study comprised 5 eyes of 3 patients whose manifest spherical equivalent was +10.5 to +18.0 diopters (D) and axial length was 15.79 to 16.82 mm. After phacoemulsification, 2 foldable acrylic IOLs with a mean power of +43.0 D +/- 9.5 (SD) (range +32.0 to +55.0 D) were implanted in the capsular bag. RESULTS: There were no significant intraoperative complications, and there was significant improvement in uncorrected and best corrected visual acuities after surgery. The spherical equivalent decreased significantly; however, the postoperative refraction was considerably more hyperopic than predicted in all eyes. Except for posterior synechias in 2 eyes and slight interlenticular opacification in 2 eyes, no major postoperative complications occurred during the mean follow-up of 14.8 months. CONCLUSIONS: Implanting 2 piggyback IOLs was beneficial in eyes with an extremely short axial length. However, the current system of lens power calculation markedly underestimates the required lens power, resulting in a hyperopic refractive error after surgery. The benefits of in-the-bag placement of 2 foldable lenses are questionable.
We examined the effects of the platelet-derived growth factor (PDGF) A-chain antisense oligodeoxynucleotides (ODN) on cardiovascular organ growth in stroke-prone spontaneously hypertensive rats (SHR-SP) in vivo. Expression of PDGF A-chain mRNA was higher in the aorta and kidney in 9-week-old SHR-SP than in Wistar-Kyoto (WKY) rats. A phosphorothioate-linked 15-mer antisense ODN complementary to the initiation codon region of rat PDGF A-chain mRNA and a control sense ODN were infused subcutaneously into SHR-SP/Izumo at a dose of 90 ng/g body weight/day for 28 days using an implanted ALZET pump. The PDGF A-chain antisense ODN did not affect blood pressure or body weight. The antisense ODN significantly inhibited [3H]thymidine incorporation into the DNA in the aorta and kidney but not in the heart. Infusion of the antisense ODN considerably reduced production of PDGF A-chain protein but did not affect expression of PDGF A-chain mRNA. Infusion of the antisense ODN considerably improved the arterial and renal tissue damage in SHR-SP morphologically. From these findings, it can be confirmed that suppression of PDGF A-chain by the antisense DNA is useful as a gene therapy for treating cardiovascular organ damage in hypertension.
STUDY OBJECTIVE: To evaluate the effects of epidurally administered neostigmine on pain after abdominal hysterectomy. DESIGN: Prospective, randomized, double-blind study. SETTING: Teaching hospital. PATIENTS: 45 ASA physical status I adult patients scheduled for abdominal hysterectomy. INTERVENTIONS: All patients received identical general and epidural anesthesia. At the end of the surgery, they received epidural bupivacaine (10 mg) with either saline (control group, n = 15), 5 micro g/kg (5-micro g group, n = 15), or 10 micro g/kg neostigmine (10-micro g group, n = 15). Postoperatively, 50 mg diclofenac suppository was given for pain relief on patient demand. MEASUREMENTS AND MAIN RESULTS: The time to first diclofenac administration and the number of times diclofenac was required during the first 24 postoperative hours were recorded. Pain was assessed using a 10-cm visual analog pain scale (VAS) at rest at the first diclofenac request, and at 15 and 24 hours after surgery. The time to first diclofenac administration was significantly longer (p < 0.05) in the 10-micro g group (223 +/- 15 min) than in the control (78 +/- 17 min) or 5-micro g groups (88 +/- 18 min). However, epidural neostigmine at both doses did not reduce the number of postoperative diclofenac administrations. There were no differences in VAS among the three groups. CONCLUSIONS: Epidural neostigmine of 10 micro g/kg in bupivacaine provides a longer duration of analgesia than does bupivacaine alone or with 5 micro g/kg of neostigmine after abdominal hysterectomy.
6-Hydrazinopyridine-3-carboxylic acid (HYNIC) constitutes one of the most attractive reagents to prepare (99m)Tc-labeled polypeptides and peptides of various molecular weights in combination with two tricine molecules as coligands. Indeed, (99m)Tc-HYNIC-conjugated IgG showed biodistribution of radioactivity similar to that of (111)In-DTPA-conjugated IgG. However, recent studies indicated significant plasma protein binding when the (99m)Tc labeling procedure was expanded to low molecular weight peptides. In this study, pharmacokinetics of (99m)Tc-HYNIC-conjugated IgG, Fab and RC160 using tricine were compared with their radioiodinated counterparts to evaluate this (99m)Tc-labeling method. In mice, [(99m)Tc](HYNIC-IgG)(tricine)(2) and [(99m)Tc](HYNIC-Fab)(tricine)(2) showed persistent localization of radioactivity in tissues when compared with their (125)I-labeled counterparts. [(99m)Tc](HYNIC-IgG)(tricine)(2) eliminated from the blood at a rate similar to that of (125)I-labeled IgG, while [(99m)Tc](HYNIC-Fab)(tricine)(2) showed significantly slower clearance of the radioactivity than (125)I-labeled Fab. On size-exclusion HPLC analyses, little changes were observed in radiochromatograms after incubation of [(99m)Tc](HYNIC-IgG)(tricine)(2) in murine plasma. However, [(99m)Tc](HYNIC-Fab)(tricine)(2) and [(99m)Tc](HYNIC-RC160)(tricine)(2) demonstrated significant increases in the radioactivity in higher molecular weight fractions in plasma. Formation of higher molecular weight species was reduced when [(99m)Tc](HYNIC-RC160)(tricine)(2) was stabilized with nicotinic acid (NIC) to generate [(99m)Tc](HYNIC-RC160)(tricine)(NIC). [(99m)Tc](HYNIC-RC160)(tricine)(NIC) also demonstrated significantly faster clearance of the radioactivity from the blood than [(99m)Tc](HYNIC-RC160)(tricine)(2). These findings suggested that one of the tricine coligands in (99m)Tc-HYNIC-labeled (poly)peptides would be replaced with plasma proteins to generate higher molecular weight species that exhibit slow blood clearance. In addition, the molecular sizes of parental peptides played an important role in the progression of the exchange reaction of one of the tricine coligands with plasma proteins.
A 49-year-old woman presented with left visual disturbance. No signs of Cushing's disease were evident. Basal levels of serum cortisol and plasma adrenocorticotropic hormone (ACTH) were 16.8 microg/dL and 66.0 pg/mL, respectively. MRI demonstrated an irregularly shaped large pituitary tumor, and the patient then underwent transsphenoidal surgery. By light microscopy the tumor represented a chromophobic adenoma with a few of the adenoma cells showing immunoreactivity for ACTH. On the basis of clinical and light microscopic examinations, the diagnosis of silent corticotroph adenoma was made. Electron microscopy, however, demonstrated the honeycomb Golgi complex that has been reported as a typical finding of gonadotroph adenomas. MRI taken 7 months after the first operation revealed adenoma regrowth. Transcranial surgery was performed, and histology demonstrated a chromophobic pituitary adenoma with most cells immunopositive for ACTH. She was treated with gamma knife postoperatively. Three months later, MRI revealed remarkable shrinkage of the adenoma, but she developed typical signs and symptoms of Cushing's disease. Thus, the hormone immunostaining and biological activity of pituitary adenomas may change with time.
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BACKGROUND/PURPOSE: Congenital motor dysfunction of the intestine associated with a morphologically abnormal myenteric nervous plexus (MP) is known as Hirschsprung's disease allied disorder (HAD). However, the clinicopathologic features of HAD are not well understood, partially because a standardized method of histologic evaluation of MP has not been established. To elucidate the clinicopathologic relationship of HAD the authors reviewed 6 cases of HAD using a newly devised histologic evaluation method. METHODS: Flat-mounted frozen sections of the ileum were stained for S-100 protein by fluorescent immunohistochemistry. Quantitative evaluation of MP was performed by measuring the fluorescence-positive area (MP ratio), and the results were compared with those of age-matched normal controls. RESULTS: All of 6 patients required laparotomy within 1 month after birth and enterostomy between 23 days and 10 months. Three died of intractable enteritis by the age of 2.2 years and were totally dependent on parenteral nutrition (PN) throughout their lives. The other 3 have survived for 6 to 10 years but have required PN occasionally. MP ratio in controls was more than 0.34 at all ages, whereas that in HAD was significantly lower than that in controls according to the clinical severity. CONCLUSION: MP size measured on 2-dimensional demonstration is suggested to be an indicator of clinical severity of HAD. J Pediatr Surg 36:898-900.
Roxatidine acetate hydrochloride (ROX, 2-acetoxy-N-[3-[m-(1-piperidinylmethyl)phenoxy]propyl]acetamide hydrochloride, CAS 78273-80-0), a histamine 2 (H2)-receptor antagonist, has been clinically applied for the treatment of gastritis, gastric and duodenal ulcers. There is no report on the identification of the metabolic enzyme of M-1 (2-hydroxy-N-[3-[m-(1-piperidinylmethyl)phenoxy]propyl]acetamide), the pharmacologically active metabolite, in humans. In this study, the Cytochrome P450 (CYP or P450) enzymes which participate in the metabolism of ROX were identified using human liver microsomes and S9 fractions. M-1 was converted to M-4 (3-[m-(1-piperidinyl-methyl)phenoxy]propylamine) by the enzyme reaction with the S9 but not with microsomes. M-4 was further metabolized to M-5 (3-[m-(1-piperidinylmethyl)phenoxy]propanol) by microsomes. The metabolism was inhibited by coumarin and anti-CYP2A1 serum. (3-[m-(1-piperidinylmethyl)-phenoxy]propionic acid) and M-3 (m-(1-piperidinylmethyl) phenol) formation from M-5 were inhibited by quinidine and anti-CYP2D6 serum. Moreover, M-5 was converted to M-2 and M-3 by cDNA-expressed CYP2D6. In conclusion, this study shows that microsomal enzymes do not participate in the clearance of the active metabolite M-1, CYP2A6 primarily catalyzes M-5 formation from M-4, and CYP2D6 primarily catalyzes M-2 and M-3 formation from M-5 in humans.
We report a new variant type of Gaucher's disease characterized by hydrocephalus, corneal opacities, deformed toes, gastroesophageal reflux, and fibrous thickening of splenic and hepatic capsules. This patient had 1 D409H allele. He differed from other reported cases with a 1342G to C (D409H) homozygous mutation (onset at 4 months, no cardiac involvement until the age of 12 years, and massive hepatosplenomegaly with fibrous thickening of spleen and liver capsules). Enzyme replacement therapy was given for 4 years, resulting in an improvement of visceral and hematologic abnormalities but no neurologic improvement.
BACKGROUND: Cisplatin (CDDP) plays an important role in the treatment of transitional-cell carcinoma (TCC), but resistance develops. The mechanism is not entirely understood. METHODS: To assess acquired resistance to CDDP, we established a CDDP-resistant subclone, CL8-2, of T24, which is a bladder cancer cell line. We examined the changes in the various pathways leading to apoptosis in the parent line and CL8-2. RESULTS: The drug caused apoptosis of T24 cells but not CL8-2 cells. The CL8-2 cells were 6.4 times more resistant to CDDP than was T24. In both cell lines, the mismatch repair genes hMLH-1 and hMSH-2 were expressed at high levels. The p53 protein was not detected in either cell line but p73 protein was induced by CDDP treatment in T24 cells, which was followed by activation of caspases 3, 8, and 9. This phenomenon was not observed in CL8-2 cells. CONCLUSION: These results suggest that loss of p73 induction may lead to CDDP resistance of TCC.
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IMPLICATIONS: We describe three patients in whom hiccups were treated successfully by atropine. Although further clinical investigation is needed, atropine may be useful in the treatment of hiccups after the laryngeal mask airway insertion.
BACKGROUND: This in vivo study had two primary objectives. The first goal was to determine whether the pulmonary vascular effects of propofol depend on the preexisting level of vasomotor tone, and the second was to investigate the effects of propofol on the pulmonary vascular responses to sympathetic alpha- and beta-adrenoreceptor activation. METHODS: Thirty-one mongrel dogs were chronically instrumented to measure the left pulmonary vascular pressure-flow (LPQ) relation. Left lung autotransplantation (LLA) was also performed in eight additional dogs to induce a long-term increase in pulmonary vascular resistance. LPQ plots were measured on separate days in the conscious state and during propofol anesthesia. LPQ plots were measured at baseline and when vasomotor tone was acutely increased with the alpha agonist, phenylephrine, or the thromboxane mimetic, U46619. In separate experiments, cumulative dose-response curves to alpha- (phenylephrine) and beta- (isoproterenol) adrenoreceptor agonists were generated in conscious and propofol-anesthetized dogs. RESULTS: Compared with the conscious state, propofol had no effect on the baseline LPQ relation in normal or post-LLA dogs. However, propofol caused pulmonary vasoconstriction (P < 0.05) when vasomotor tone was acutely increased with either phenylephrine or U46619 in normal or post-LLA dogs. The pulmonary vasoconstrictor response to alpha-adrenoreceptor activation was potentiated (P < 0.05) during propofol anesthesia, whereas the pulmonary vasodilator response to beta-adrenoreceptor activation was not altered. CONCLUSION: These results indicate that the pulmonary vascular response to propofol anesthesia is tone-dependent. During sympathetic activation, propofol may favor alpha-adrenoreceptor-mediated vasoconstriction over beta-adrenoreceptor-mediated vasodilation.
We present two patients with bleeding episodes from gastric fundal varices. The gastric fundal varices were treated by balloon catheter-assisted endoscopic sclerotherapy using alpha-cyanoacrylate monomer. The varices were successfully obliterated with no complications or hemodynamic changes to the gastrorenal shunts. This procedure may be considered a novel, feasible approach to the treatment of gastric fundal varices in the future.
BACKGROUND: Spontaneously hypertensive rats (SHR)-derived vascular smooth muscle cells (VSMC) show exaggerated growth and increasingly express platelet-derived growth factor (PDGF) A-chain mRNA compared to VSMC from normotensive Wistar-Kyoto (WKY) rats. OBJECTIVE: To investigate the effects of designed DNA-RNA chimeric hammerhead ribozyme to rat PDGF A-chain on exaggerated growth of VSMC from SHR. DESIGN AND METHODS: We designed and synthesized a 38-base DNA-RNA chimeric hammerhead ribozyme with two phosphorothioate linkages at the 3' terminal to cleave rat PDGF A-chain mRNA at the GUC sequence at nucleotide 921. We confirmed the cleavage activity of designed ribozyme by in vitro cleavage reaction and by lipofectin-mediated transfection of ribozyme into VSMC. RESULTS: Doses of 0.1 and 1 micromol/l DNA-RNA chimeric ribozyme dose-dependently inhibited basal DNA synthesis in VSMC from SHR. A dose of 1 micromol/l DNA-RNA chimeric ribozyme time-dependently inhibited basal DNA synthesis in VSMC from SHR. However, the same doses of all-RNA ribozyme had no effects on DNA synthesis in VSMC from SHR. Fluorescein isothiocyanate-labeled DNA-RNA chimeric ribozyme was recognized in cytosol at 30 min, and in nucleus at 60 min after lipofectin transfection. A dose of 1 micromol/l DNA-RNA chimeric ribozyme significantly inhibited expressions of both PDGF A-chain mRNA and PDGF-AA protein in VSMC from SHR, but not from WKY rats. CONCLUSION: These results indicated that the designed DNA-RNA chimeric ribozyme to PDGF A-chain mRNA effectively and specifically inhibited the exaggerated growth of VSMC from SHR at low concentrations, which were mediated by the reduction of PDGF A-chain mRNA and PDGF-AA protein expressions.
BACKGROUND: Angiotensin II (Ang II) has been reported to inhibit insulin signaling at multiple levels in vascular smooth muscle cells (VSMC) in vitro. We have demonstrated that VSMC from spontaneously hypertensive rats (SHR) produce Ang II in a homogeneous culture. OBJECTIVE: In the current study, we investigated influences of endogenous Ang II on insulin signaling in VSMC from SHR. DESIGN AND METHODS: Phosphatidylinositol 3-kinase (PI3-kinase) activity, insulin receptor substrate-1 (IRS-1) associated tyrosine phosphorylation, and p85 subunit of PI3-kinase were measured in VSMC from SHR and normotensive Wistar-Kyoto (WKY) rats in the absence and presence of Ang II type 1 receptor antagonist RNH6270 and mitogen-activated protein kinase/extracellular signal-regulated kinase (MEK) inhibitor U0126. RESULTS: Insulin treatment increased PI3-kinase activity in VSMC from WKY rats in a dose-dependent manner. In contrast, insulin treatment of VSMC from SHR did not affect PI3-kinase activity. However, co-treatment of VSMC from SHR with RNH6270 and insulin, increased PI3-kinase activity. PI3-kinase activity, IRS-1-associated tyrosine phosphorylation and p85 subunit of PI3-kinase in VSMC from WKY rats decreased in response to treatment with Ang II and returned to control levels upon co-treatment with U0126. Basal levels of PI3-kinase activity, IRS-1-associated tyrosine phosphorylation, and p85 subunit of PI3-kinase were significantly lower in VSMC from SHR than in cells from WKY rats. U0126 treatment of VSMC from SHR significantly increased levels of PI3-kinase activity, IRS-1-associated tyrosine phosphorylation, and p85 subunit of PI3-kinase. CONCLUSION: These results indicate that endogenous Ang II suppresses insulin signaling in VSMC from SHR by activating extracellular signal-regulated kinase. These findings suggest that tissue Ang II may play a role in insulin resistance in hypertension.