Effect of growth hormone on growth failure and bone loss induced by supraphysiologic dose of glucocorticoid in rats.
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Biomedical subjects
Publications and source records attributed to Y Kaji.
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We studied a new technique for creating long linear lesions in hearts using a custom-made linear probe. Radiofrequency (RF) energy applications using a 25-mm long stainless steel linear probe and a corresponding 500-kHz energy generator were tested, creating 90 lesions in isolated porcine hearts. The RF current was applied between the linear probe and a large patch electrode attached to the back of the specimen. Three parameters, comprising the power of the delivered energy, the pressure of contact between the probe and the specimen, and the duration of energy delivery were changed independently and the size of the resulting lesions was measured. All 90 lesions were transmural, well demarcated and created by a single stationary RF application. Lesion length and width increased with: 1) increasing power, when the other two parameters were maintained at constant levels, 2) increasing contact pressure, when the other two parameters were maintained at constant levels, and 3) increasing duration of energy delivery when the other two parameters were maintained at constant levels. The maximum width of the lesions was 3.7 mm. No overheating of any of the specimens was observed. In conclusion, the new original long linear probe used in this study was effective for creating transmural linear lesions, presenting the possibility of a worthwhile contribution to the maze surgical procedure applied to atrial fibrillation.
We report a case of dermatomyositis (DM) associated with invasive thymoma in a 22-year-old woman who was admitted to our hospital complaining of dyspnea which required ventilation support. The reddened elevated scaly eruptions were prominent over the extensor surfaces. Chest X-ray and computed tomography showed mediastinal masses, which were diagnosed as mixed type thymoma. Muscle and skin biopsy specimens were compatible with DM. She was treated with methylprednisolone pulse therapy followed by extended removal of the anterior mediastinal tumor and subsequent radiotherapy. She has had a good clinical course without recurrence of thymoma or DM for more than 3 years. The role of thymoma in the development of DM is discussed.
PURPOSE: Hyaluronan (HA), a high-molecular-weight linear glycosaminoglycan, is a component of the extracellular matrix (ECM). It is expressed in eyes and plays important roles in many biologic processes, including cell migration, proliferation, and differentiation. Hyaluronan is produced by HA synthase (HAS), which has three isoforms: HAS1, HAS2, and HAS3. In this study, the HAS expression in the anterior segment of bovine eyes was investigated to determine the significance of HA in eyes. METHODS: To obtain bovine HAS probes, degenerate oligonucleotide primers, based on well-conserved amino acid sequences including the catalytic region of each HAS isoform, were used for reverse transcription-polymerase chain reaction to amplify mRNA from bovine corneal endothelial cells (BCECs). Hyaluronan synthase-1 expression in the anterior segment of bovine eyes at the protein level was investigated by immunohistochemistry. RESULTS: All three HAS isoforms were expressed in BCECs at the mRNA level. Amplified cDNA fragments of HAS1, HAS2, and HAS3 from BCECs can be aligned to human counterparts, showing similarities of 100%, 97.3%, and 100%, respectively, at the amino acid level. Hyaluronan synthase 1 was expressed at the protein level in corneal epithelium, keratocyte, corneal endothelium, conjunctival epithelium, ciliary epithelium, capillary endothelium, and trabecular meshwork. CONCLUSIONS: Hyaluronan synthase isoforms were expressed in the ocular anterior segment and are speculated to be involved in HA production in situ.
PURPOSE: To evaluate the long-term outcome of 2% topical cyclosporine A (CsA) treatment as an adjunct to topical corticosteroid in 86 eyes after penetrating keratoplasty (PK). MATERIAL AND METHODS: The subjects were 86 eyes of 83 patients who had undergone PK and received topical CsA treatments. Ninety-seven eyes of 95 patients who had undergone PK and received similar postoperative treatments except for topical CsA treatments served as control: The clinical outcome of PK was evaluated by rates of graft survival and rejection-free graft survival using Kaplan-Meier's method and compared with the log-rank test. The patients were subdivided into high-risk and low-risk groups. The high-risk patients were those who had corneal vascularization in 2 or more quadrants of the cornea preoperatively or who received regrafting. All other patients were assigned to the low-risk group. Thirty-six eyes of the CsA group and 50 eyes of the control group were high-risk cases. RESULTS: In the high-risk patients, the rejection-free graft survival rate was 69.7% in the CsA group and 45.4% in the control group (p = 0.030). However, there was no significant difference in the graft survival rate between the two groups. In the low-risk patients, there was no significant difference in the rates of rejection-free graft survival and graft survival between the CsA and the control group. CONCLUSION: 2% topical cyclosporine is effective in reducing the risk of allograft rejection in high-risk recipients.
There are only a few reports on successful radiofrequency catheter ablation of idiopathic right ventricular tachycardia (VT) originating from other sites than right ventricular outflow tract. We report here a case of VT which exhibited an inferior-axis and a left bundle branch block pattern and originated near the His bundle. Using the temperature-controlled ablation catheter, prudent observation of the fluoroscopy and intracardiac electrograms during pacemapping, we successfully ablated the origin of the VT without any conduction disturbance. However, further study is required to determine the effectiveness of catheter ablation and the long term prognosis for this type of VT.
The formation of multinucleated giant cells (MGCs) from monocytes/macrophages is controlled by various cytokines whose crucial roles are not fully understood. In this study, we found that interleukin (IL)-13 as well as IL-4 induced peripheral blood monocytes (PBMs) and monoblastic cell line, UG3, to differentiate into MGCs in the presence of macrophage colony-stimulating factor (M-CSF), while IL-2, IL-7 or IL-10 did not. The presence of M-CSF was essential to this MGC formation, because IL-3 or granulocyte-macrophage colony-stimulating factor (GM-CSF) could not replace M-CSF. IL-4 and IL-13 have been known to inhibit the formation of osteoclast-like cells in the presence of stroma cells or osteoblastic cells. But in our system without stroma cells, IL-4 or IL-13 induced some of characteristics of osteoclasts such as tartrate-resistant acid phosphatase (TRAP) activity, vitronectin receptor (vit-R) expression and resorptive activity for hydroxyapatite, but not the expression of receptors for parathyroid hormone or calcitonin. These results suggest possible involvement of IL-4 and IL-13 in MGCs and osteoclasts development, and UG3 may be useful to further investigate the roles of IL-4 and IL-13 in the formation and physiology of MGCs, and the relationship between these MGCs and osteoclasts.
BACKGROUND: Transforming growth factor beta (TGF-beta) regulates extracellular matrix deposition, cell proliferation, and migration, and is expressed in cornea. TGF-beta is thought to be involved in the corneal wound healing process. METHODS: The central corneal area (3 mm in diameter) of Lewis rats was ablated using PTK mode excimer laser and the wound healing process was observed at 12 and 24 h and 2, 5, 10, and 30 days after treatment. The expression of TGF-beta 1, -beta 2 and -beta 3, TGF-beta type I and type II receptors, alpha 3, alpha 5, beta 4 integrin subunits, laminin and fibronectin was studied immunohistochemically. Antibody neutralizing TGF-beta 1, -beta 2 and -beta 3 was administered intraperitoneally, 50 micrograms daily, for 5 days after the laser treatment to investigate the effects of TGF-beta function blockade. RESULTS: At the leading edge of the regenerating epithelium, no TGF-beta type I and type II receptors and beta 4 integrin subunits were expressed after 24 h. Regenerating epithelium covered the ablated area after 2 days. An abnormal fibrotic layer was formed in the subepithelial area. This layer contained round-shaped cells in the stroma in the early stage (2-5 days after laser ablation) and spindle-shaped fibroblast-like keratocytes after 10 days. Laminin and fibronectin expression increased in the fibrotic layer. The increased stromal cells expressed TGF-beta isoforms and TGF-beta receptors. Neutralizing TGF-beta inhibited the stromal cell increase in the laser ablated area after 5 days. CONCLUSION: TGF-beta may be involved in epithelial cell migration and stromal cell reaction during the corneal wound healing process after excimer laser ablation in rat models.
PURPOSE: To investigate the structural changes in corneal stromal collagen fibrils after excimer laser keratectomy in relation to the degree of corneal haze. SETTING: University of Tokyo Hospital, Tokyo, Japan. METHODS: Corneal haze was quantitatively measured by analyzing the light scattering in Scheimpflug images of the corneas of white rabbits after excimer laser keratectomy. Collagen fibril structure was examined using scanning electron microscopy after chemical digestion with sodium hydroxide solution; the same specimens were examined by transmission electron microscopy after re-embedding. RESULTS: Corneal haze reached a peak 4 weeks after excimer laser keratectomy and then gradually decreased. The collagen fibrils of the normal cornea were regularly arranged parallel to the surface of the cornea, with small interfibrillar distances. After excimer laser keratectomy, the arrangement was highly disordered, with increased interfibrillar distances. These structural changes were most prominent 4 weeks after excimer laser keratectomy. CONCLUSION: The structural changes in the collagen fibrils of the corneal stroma, especially the increase in interfibrillar distances and the disordered arrangement, were associated with corneal haze after excimer laser keratectomy.
The purpose of this study is to determine whether short-term preadministration of bisphosphonates prevents bone loss in rat proximal tibial metaphysis when induced by hindlimb immobilization by bandage. Six-month-old female Sprague Dawley rats were injected with incadronate disodium (YM-175, 10 micrograms/kg) or vehicle, three times per week for 2 weeks (YM or V groups). Then, the left hindlimb was fixed to the abdomen with a bandage (V-B, YM-B groups), or only the abdomen was bandaged as control (V-SHM, YM-SHM groups), for 4 weeks. The animals were subsequently killed and left proximal tibiae were processed undecalcified for quantitative histomorphometric evaluation. Immobilization-induced cancellous bone loss resulted not only from increased percent eroded surface area but also from decreased percent labeling surface and bone formation rate in V-B compared with V-SHM animals. In contrast, preadministration of YM-175 decreased percent eroded surface significantly and prevented the loss of cancellous bone mass in YM-B compared with V-B animals. Cancellous bone mass was neither increased nor decreased by preadministration of YM-175 in YM-SHM animals. Our results suggest that preadministration of bisphosphonates is effective in prevention of bone loss at the tibial metaphysis when induced by hindlimb immobilization in rats.
Idiopathic ventricular tachycardia (VT) originating from the left ventricular outflow tract (LVOT) is rare. We report two patients whose QRS configuration during VT commonly showed an inferior axis and monophasic R waves in all the precordial leads. The mechanism of these VTs appeared to be triggered activity. From mapping and ablation, the origin of these VTs was determined to be in the most posterior LVOT, corresponding to the aortomitral continuity (left fibrous trigone).
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PURPOSE: To assess whether magnetic resonance (MR) spectroscopic imaging with MR imaging can improve prostate cancer localization in postbiopsy hemorrhage cases. MATERIALS AND METHODS: Records of 175 patients with prostate cancer were retrospectively reviewed; 42 patients (135 hemorrhagic sites) had spatially correlated biopsy data. Patients underwent both phased-array coil-endorectal coil MR imaging and three-dimensional MR spectroscopic imaging within 180 days after transrectal ultrasound (US)-guided biopsy. High-signal-intensity hemorrhage on T1-weighted images and corresponding high- or low-signal-intensity areas on T2-weighted images and the metabolic ratio (choline + creatine)/citrate were recorded. Cancer was identified as a low-signal-intensity area at T2-weighted MR imaging or a metabolite ratio greater than 3 standard deviations above normal at MR spectroscopic imaging. MR imaging, spectroscopic, and biopsy findings were compared. RESULTS: Forty-nine patients had postbiopsy hemorrhage. On T2-weighted images, a higher (P < .01) percentage of hemorrhagic sites demonstrated low signal intensity (80% [108 of 135 sites]), which is similar to the signal intensity seen with cancer. The addition of MR spectroscopic imaging to MR imaging resulted in a significant increase (P < .01) in the accuracy (52% to 75%) and specificity (26% to 66%) of tumor detection. CONCLUSION: The addition of MR spectroscopic imaging to MR imaging significantly improves the ability to determine the presence of prostate cancer and spatial extent when postbiopsy changes hinder interpretation with MR imaging alone.
Since the mechanism of creatine kinase (CK) leakage induced by beta-adrenoceptor activation remains unclear, we studied the effects of incremental application (10(-9) to 10(-4) M) of isoproterenol (ISP) on the CK efflux from Langendorff-perfused isolated rat hearts under aerobic conditions. Tissue water content was estimated after the perfusion experiment. ISP-induced dose-dependent CK leakage was noted in a sigmoidal fashion, which showed low temperature-dependency (Q10 of 2.41), sensitivity to cepharantine (10(-6) M) and propranolol (10(-7) to 10(-6) M) without any signs of demand ischemia or oxidant stress. CK liberation was not replicated at all by maneuvers activating cAMP-dependent protein kinase (A-kinase). Myocardial edema noted in the control ISP application was ameliorated by exposure to 10(-6) M propranolol or cepharantine (i.e., significant fall in tissue water content; p < 0.05). Histological study revealed nonspecific myocardial fiber swelling and separation without any myocyte necrosis for all the perfusion groups. These results suggest that ISP-induced CK leakage in this model is not mediated by beta-adrenoceptor stimulation, subsequent A-kinase activation or related demand ischemia, but is attributed most to the direct effects of ISP augmenting sarcolemmal CK and water permeability.
Ventricular arrhythmia observed in the acute stage of myocardial infarction is profoundly related to the autonomic balance. To investigate prediction of ventricular arrhythmia, heart rate variability and plasma catecholamine concentration were simultaneously measured for a week in 17 consecutive patients with first anterior or anteroseptal Q wave infarction treated without specific coronary intervention. The cross-sectional plot of coefficient of variance (= standard deviation of N-N interval/mean N-N interval x 100; %) as a function of plasma epinephrine on the day of admission remained lower than the standard average. Ventricular premature contractions increased in proportion to the plasma epinephrine concentration. In the first week of hospitalization, plasma epinephrine concentration and frequency of premature contraction decreased exponentially, whereas the coefficient of variance showed a modest decline. Ventricular tachycardia refractory to xylocaine with rate accelerating with persistence was observed only in patients with the peak epinephrine concentration > 375 pg/ml. Plasma epinephrine concentration rather than coefficient of variance during sleep after the first acute episode is more closely related to the following triggered ventricular arrhythmia.
PURPOSE: Production of extracellular matrix (ECM) by corneal endothelial cells is related to physiologic functions and pathologic conditions and is regulated by many cytokines, including transforming growth factor-beta (TGF-beta). In this study, the molecular mechanism of ECM production regulation by TGF-beta was investigated in cultured corneal endothelial cells. METHODS: The production of ECM components (laminin and fibronectin) was detected in cultured corneal endothelial cells by western blot analysis. To determine the signal transduction pathways, mutant TGF-beta type I receptor (TbetaR-I) and/or Smad protein family members (intracellular signal transducers in TGF-beta signaling) were overexpressed by transfecting their cDNA into the cultured cells, and the effects on ECM production were observed. RESULTS: The production of laminin and fibronectin was stimulated by treatment with TGF-beta1 or TGF-beta2. After transient transfection of cDNA of the constitutively active (CA) mutant of TbetaR-I, the production of laminin and fibronectin was stimulated even in the absence of TGF-beta. The transfection of the dominant negative mutant of TbetaR-I counteracted the effects of TGF-beta. These results confirm that TGF-beta directly stimulates ECM production from corneal endothelial cells through TbetaR-I. The ECM production stimulation by TGF-beta or CA TbetaR-I was accelerated by the overexpression of Smad2, Smad3, and/or Smad4 and inhibited by that of Smad7. These results show that TGF-beta signals connected to ECM production are regulated by Smad family members, located downstream of TbetaR-I. CONCLUSIONS: The results of this study show that TGF-beta stimulates ECM production from corneal endothelial cells through TbetaR-I and Smad family transducers.
Radiofrequency (RF) catheter ablation was tried to treat a patient with syncope, perhaps due to polymorphic ventricular tachycardia (VT) of Torsade de Pointes (TdP) type which was documented by Holter monitoring. Electrophysiological study showed that the isolated ventricular extrasystoles (VEs) that initiated TdP were exactly replicated by pace mapping at the septal site of the right ventricular outflow tract. Performance of RF ablation at this site abolished the TdP and episodes of syncope with no requirement for antiarrhythmic agents for 3 years, whereas isolated VEs persisted. Although it is difficult to mention whether RF ablation was successful or not in this case, this procedure should be considered as a potentially curative approach to the TdP, when the arrhythmogenic focus can be fixed and identified as in this case.
BACKGROUND: Aminoaciduria is found in Lowe's syndrome. No studies of concentrations of ascorbic acid and amino acids in the aqueous humor of the syndrome have been performed. We examined these concentrations in a patient with Lowe's syndrome. METHODS: Ascorbic acid and amino acid levels in the aqueous humor and plasma of a male infant were measured by means of high-performance liquid chromatography. The patient, who had congenital cataract, miotic pupils, opaque corneas, glaucoma, aminoaciduria, normal levels of ascorbic acid and amino acid in the plasma, and renal tubular acidosis, underwent trabeculotomy, lensectomy, and anterior vitrectomy in both eyes. RESULTS: Intraocular pressure in both eyes decreased to within the normal range, but both corneas remained opaque. The amino acid levels in the aqueous humor were similar to those in the plasma, but intracameral ascorbic acid levels were decreased. After topical instillation of ascorbic acid, the corneas became transparent. The proband's mother had good visual acuity but paracentral lens opacities in both eyes. His maternal grandmother had scattered cortical opacities in both lenses. CONCLUSION: In this infant with Lowe's syndrome, we found intracameral levels of amino acids similar to those in the plasma. Levels of ascorbic acid in the aqueous humor were decreased.