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Biomedical subjects

T Harada

Publications and source records attributed to T Harada.

At least 127 records · Page 7Linked to original sources

Two classes of enzymes of opposite stereochemistry in an organism: one for fluorinated and another for nonfluorinated substrates.

Reduction of methyl ketones by dried cells of Geotrichum candidum (APG4) afforded (S)-alcohols in excellent enantiomeric excess (ee), whereas the reduction of trifluoromethyl ketones gave the corresponding alcohols of the opposite configuration also in excellent ee. The replacement of the methyl moiety with a trifluoromethyl group alters both the bulkiness and the electronic properties, the effect of which on the stereoselectivity was examined. No inversion in stereochemistry was observed in the reduction of hindered ketones such as isopropyl ketone, while the stereoselectivity was inverted in the reduction of ketones with electron-withdrawing atoms such as chlorine. The mechanism for the inversion in stereochemistry was investigated by enzymatic studies. Several enzymes with different stereoselectivities were isolated; one of them catalyzed the reduction of methyl ketones, and another with the opposite stereoselectivity catalyzed the reduction of trifluoromethyl ketones. Furthermore, both APG4 and the isolated enzyme were applied to the reduction of fluorinated ketones on a preparative scale, which resulted in the synthesis of chiral fluorinated alcohols with excellent ee.

Fluorine↗

Oil-soluble versus water-soluble media for assessing tubal patency with hysterosalpingography or laparoscopy in subfertile women.

BACKGROUND: There has been debate in the literature for more than 40 years as to whether flushing of the Fallopian tubes enhances fertility and whether this presumed therapeutic effect is greater with oil-soluble media than with water-soluble media. A meta-analysis of the therapeutic role of oil-soluble contrast media at hysterosalpingography was published in March 1994 (Watson 1994). This Cochrane Review is an expansion and update of that overview. OBJECTIVES: To evaluate the effect of flushing the Fallopian tubes with oil- or water-soluble contrast media on subsequent pregnancy rates in infertility patients. SEARCH STRATEGY: 1. For randomised controlled trials (RCTs): we searched the Cochrane Subfertility Review Group specialised register of controlled trials. 2. For non-randomised controlled studies: Medline and manual search of eight relevant journals. SELECTION CRITERIA: Six RCTs and six non-randomised controlled studies. In two studies tubal flushing was compared with no treatment-controls. Eleven studies, comprising a total of 2635 subjects, compared oil- with water-soluble media. DATA COLLECTION AND ANALYSIS: Independently by first 2 authors for: 1. Methodological trial characteristics 2. Characteristics of participants 3. OUTCOMES: the main studied outcome was pregnancy rate per patient MAIN RESULTS: In comparison with no treatment, a significant benefit on pregnancy rates was seen by flushing the tubes with oil-soluble media (OR 1.80, 95% CI 1.29-2.50) but not with water-soluble media (OR 0.87, 95% CI 0.50-1.52). In the direct comparison of oil- and water-soluble media the former lead to significantly higher pregnancy rates (OR 1.92, 95% CI 1.60-2.29). The treatment effect appeared similar in RCTs and non-RCTs. Subgroup analysis suggested the therapeutic benefit was greatest for patients suffering from unexplained infertility and least for those with tubal factor infertility. REVIEWER'S CONCLUSIONS: Flushing of the tubes with oil-soluble media increases subsequent pregnancy rates in infertility patients. The hypothesis that tubal "plugs" are a cause of proximal tubal occlusion and that oil-soluble media may flush them out, is supported by new techniques such as falloposcopy. Clinicians should consider flushing the tubes with OSCM before contemplating more invasive therapies.

Contrast Media↗

Thoracolithiasis.

Thoracolithiasis without any history of chest traumas or interventions is pathologically rare, with only 9 cases including our 2, reported thus far in the literature. Case 1: A 76-year-old man admitted to our hospital had an abnormal shadow in chest radiography that gradually enlarged. Serum carcinoembrionic antigen was slightly elevated during follow-up. A milky white tumor 1.5 cm in diameter with many projections was found in the thoracic cavity and removed by thoracoscopy. Histopathological examination showed the tumor to consist of fibrous tissue with fatty necrosis at the core. Case 2: A 54-year-old woman admitted to our hospital had an abnormal shadow in chest screening radiography in 1998. Transbronchial biopsy showed this shadow to be lung adenocarcinoma. A small trigonal pyramid-shaped milky white nodule 5 mm in diameter was found in the thorax during lobectomy for lung cancer. Histopathological examination showed this nodule also to consist of fibrous tissue with fatty necrosis.

Aged↗

Transsternal bilateral thoracotomy for pericardiectomy after coronary artery bypass grafting.

Surgery for constrictive pericarditis was conducted through a transsternal bilateral thoracotomy in a 45-year-old man who developed the condition 12 months after coronary artery bypass grafting with left internal thoracic artery and vein grafts. The grafts ran just beneath the sternum. To avoid injury to the bypass grafts during sternotomy and mediastinal dissection, we conducted a transsternal bilateral thoracotomy, which provided excellent exposure of the heart. Complete pericardiectomy was done safely without cardiopulmonary bypass. Constrictive pericarditis following cardiac surgery is an uncommon complication posing difficult problems for the surgeon. The presence of a patent left internal thoracic artery bypass is particularly challenging. Transsternal bilateral thoracotomy is a useful approach in patients with constrictive pericarditis in whom a median sternotomy is contraindicated.

Coronary Artery Bypass↗

Pathologic changes in the common bile duct of an experimental model with pancreaticobiliary maljunction without biliary dilatation.

Pancreaticobiliary maljunction (PBM), a congenital anomaly, causes regurgitation of pancreatic juice into the biliary tract, where it exerts a hazardous influence. However, changes in the common bile duct (CBD) remain obscure due to a lack of suitable experimental models. Using cats, we have developed an experimental model of PBM without bile-duct dilatation that allows the pure effects of PBM to be studied. Histologic and cellular kinetic changes in the CBD were analyzed in 6 controls and 9 experimental animals that survived for more than 6 months. CBD sections were stained with hematoxylin and eosin and a monoclonal antibody to the proliferating cell nuclear antigen (PCNA). Invaginations of the bile-duct epithelium or parietal sacculi increased, and peribiliary glands were well-developed. PCNA-positive cells significantly increased in the CBD, especially in the parietal sacculi and glands. It is concluded that PBM increases the cell cycle in CBD epithelium and subsequently developed peribiliary glands. These developed glands may be associated with the formation of protein plugs, often seen in patients with PBM.

Animals↗

Involvement of muscarinic cholinergic and alpha2-adrenergic mechanisms in growth hormone secretion during exercise in humans.

The purpose of this study was to examine the role of muscarinic cholinergic and alpha2-adrenergic mechanisms in growth hormone (GH) secretion during exercise in humans. The GH responses induced during moderate-intensity exercise (using a cycle ergometer at 60% maximal oxygen uptake, VO2max, for 30 min) without treatment (control) and after the administration of a muscarinic cholinergic antagonist (atropine 1 mg) or after an alpha2-adrenergic antagonist (yohimbine 15 mg) were compared in seven healthy men. Although, serum GH concentration had increased significantly after exercise in the control experiment [mean peak GH concentration 52.64 (SEM 18.60) ng x ml(-1)], the increase was suppressed by the administration of either atropine [mean peak GH concentration 8.64 (SEM 7.47) ng x ml(-1)] or yohimbine [mean peak GH concentration 17.50 (SEM 7.89) ng x ml(-1)]. The area under the curve of serum GH concentration against time was significantly lower in the experiment using these drugs [with atropine, mean area 458 (SEM 409) ng x ml(-1) min], with yohimbine mean area 946 (SEM 435) ng x ml(-1) min] than in the control experiment [mean area 3135 (SEM 1098) ng x ml(-1) x min]. These results suggest that muscarinic cholinergic and alpha2-adrenergic mechanisms are involved in GH secretion during exercise in humans.

Adrenergic alpha-2 Receptor Antagonists↗

Hepatectomy for cholangiocarcinoma complicated with right umbilical portion: anomalous configuration of the intrahepatic biliary tree.

The right umbilical portion (right-sided round ligament) has been discussed as an intrahepatic portal venous anomaly associated with "left-sided gallbladder" in several reports. We treated two patients with right umbilical portion (RUP) associated with cholangiocarcinoma. Left hepatectomies were performed, preserving the residual hepatic blood flow and biliary continuity. From our experience in these patients we propose the presence of anomalous configuration of the intrahepatic biliary tree in RUP, because both patients showed medial segmental bile ducts ramified from the right and left hepatic ducts. In general, although the medial segmental bile duct ramified from the left, we surmised that this abnormal bilateral drainage pattern may not be a rare phenomenon in RUP. Special attention may be required to focus on the anatomy of the portal tributaries and biliary ramifications in RUP.

Bile Duct Neoplasms↗

Bypass surgery using a radial artery graft for bilateral extracranial carotid arteries occlusion.

A patient presenting with recurrent ischemic attacks was demonstrated to have complete occlusion of the right common and left internal carotid arteries. An external carotid angiogram showed a large left superficial temporal artery (STA) supplying both sides of the scalp. 123I-IMP single photon emission computed tomography (SPECT) revealed hypoperfusion of the both hemispheres, especially the left cerebral hemisphere. An extracranial-intracranial (EC-IC) bypass was performed using a radial artery graft interpositioned between the proximal part of the STA and the M2 segment, thus preserving blood flow to the scalp through the STA. Postoperative angiography after 1 year showed good circulation through the anastomosis, and 123I-IMP SPECT studies demonstrated increased cerebral perfusion. The patient improved clinically. The surgical technique is described below.

Carotid Artery Diseases↗

Altered gene expression and secretion of interleukin-6 in stromal cells derived from endometriotic tissues.

OBJECTIVE: To compare the expression of interleukin-6 (IL-6) in endometrial and endometriotic cells. DESIGN: Prospective study. SETTING: Department of Obstetrics and Gynecology, Tottori University Hospital, Yonago, Japan. PATIENT(S): Twenty patients who underwent either hysterectomy or laparoscopic surgery. INTERVENTION(S): Endometrial and endometriotic stromal cells were obtained from normal endometrium and from chocolate cyst linings of the ovary. Peritoneal macrophages were isolated from peritoneal fluids. Cells were cultured in the presence or absence of tumor necrosis factor-alpha. MAIN OUTCOME MEASURE(S): Gene expression of IL-6 was examined by Northern blot analysis. Interleukin-6 protein production was examined by immunocytochemical staining and ELISA. RESULT(S): A single IL-6 messenger RNA band of approximately 1.3 kilobases was detected in endometriotic stromal cells. Tumor necrosis factor-alpha increased the expression of IL-6 messenger RNA in endometriotic cells in a dose-dependent manner. In endometrial stromal cells, IL-6 messenger RNA signals were much weaker. Endometriotic stromal cells produced significantly larger amounts of IL-6 compared with endometrial stromal cells under basal conditions and after stimulation with tumor necrosis factor-alpha. Interleukin-6 protein was detected in cells isolated from endometriotic tissues by immunocytochemical staining. Interleukin-6 production by cultured macrophages from patients with endometriosis and endometriotic stromal cells was comparable. CONCLUSION(S): Altered gene expression and protein secretion of IL-6 in patients with endometriosis may contribute to the pathogenesis of the disease and/or to endometriosis-associated infertility.

Adult↗

Influences of catecholamines on the sudden death induced in dogs by an antifungal agent, D0870.

We previously reported the occurrence of QT prolongation and sudden death owing to torsades de pointes (TdP) in dogs treated with D0870, an antifungal agent. In the present study, we evaluated the influences of epinephrine and isoproterenol on the onset of TdP each time D0870 was given to 6 anesthetized open-chest dogs at a dosage of 20 mg/kg, 5 times every 40 minutes, by the simultaneous measurements of surface electrocardiogram and epicardial monophasic action potential (MAP). D0870 alone induced noticeable prolongation of the QT interval and action potential duration (APD), but neither ventricular premature contraction (VPC) nor sudden death. In contrast, the additional administration of the catecholamines induced a greater shortening of APD during the later phase of repolarization than during its earlier one and VPCs in all dogs tested, and sudden deaths owing to TdPs in 4 of the 6 dogs treated with D0870. These results suggest that D0870 alone does not induce TdP but that catecholamines play an important part in the development of sudden death induced by D0870 in dogs.

Action Potentials↗

Insertion/deletion polymorphism in ACE gene is not associated with renal progression in Japanese patients with IgA nephropathy.

We determined the relationship between the gene polymorphism of angiotensin I-converting enzyme (ACE) and the progression of immunoglobulin A (IgA) nephropathy in a large cohort in a multicenter trial of ethnically homogeneous Japanese patients (n = 527). Patients with biopsy-proven IgA nephropathy were recruited from several clinics in Japan. The mean observation period was 8.4 +/- 4.7 years. ACE insertion/deletion (I/D) genotype was determined by polymerase chain reaction amplification using allele-specific primers. Clinical factors investigated in all patients were date of birth, sex, levels of urinary protein excretion, duration of observation, serum creatinine (sCr) level, and creatinine clearance (CCr). ACE genotype distribution did not differ between patients who maintained normal renal function (II, 41%; ID, 44.7%; DD, 14.3%) and those who progressed to renal impairment (II, 41.7%; ID, 40.4%; DD, 17.9%). Kaplan-Meier analysis did not show a significant difference in renal survival rate among the three groups of each genotype. In multivariate analysis, only two variables, proteinuria greater than 1.0 g/d of protein and impaired renal function (sCr >1.2 mg/dL or CCr <70 mL/min) at the time of renal biopsy, were found to be risk factors for disease progression leading to a poor outcome. No association was observed between these variables and ACE genotype. It appears that ACE I/D polymorphism may not affect the progressive deterioration of renal function in patients with IgA nephropathy from our multicenter trial.

Adult↗

Induction of rat alkaline phosphatase isozymes bearing a glycan-phosphatidylinositol anchor modified by in vivo treatment with a benzimidazole derivative linked to ethylbenzene.

Serum alkaline phosphatase (ALP) is detected in soluble-form as a result of translocation from the membrane site by cleavage at the glycosyl-phosphatidylinositol moiety (GPI anchor). It is known that membrane-bound ALP (mALP) can be detected in serum in certain pathological and physiological conditions, and that it can be solubilized in vitro to soluble-ALP (sALP) by phosphatidylinositol-specific phospholipase C (PIPLC), phospholipase D, bile salt, detergent, etc. We observed a marked increase in ALP activity in the serum of rats given a benzimidazole derivative by gavage, and detected it as slow-migrating ALPs (SM-ALPs), which were mALP-like but resistant to PIPLC and n-butanol treatment on disc PAGE. On the other hand, ficin treatment made SM-ALPs shift to the sALP position. The molecular size of the SM-ALPs was smaller than that of sALP on sodium dodecyl sulphide-polyacrylamide slab-gel electrophoresis (SDS-PAGE), and immunoreactivity revealed the intestinal type. SM-ALPs were also detected in the duodenum and jejunum. The main sugar chain structure of SM-ALPs was the biantennary complex-type, which was coincided with intestinal sALP sugar chain. These results suggest that intestinal ALPs induced by the benzimidazole derivative were modified in their C-terminus or GPI anchor region and modification of this region may also participate in translocation into the bloodstream.

Alkaline Phosphatase↗

Immunohistochemical localization of cytokines and cell adhesion molecules in maxillary sinus mucosa in chronic sinusitis.

OBJECTIVE: Chronic sinusitis is a common disease characterized by persistent inflammation of the nasal and paranasal sinus mucosa. Accumulating evidence supports the importance of proinflammatory cytokines and endothelial cell adhesion molecule (CAM) expression as an initiating process in tissue inflammation. This study was conducted to investigate the localization of major cytokines and CAMs in the maxillary sinus mucosa from patients with chronic sinusitis and from normal subjects. METHODS: Maxillary sinus mucosal specimens from patients with chronic sinusitis (n = 10) and from normal subjects (n = 6) were immunostained with specific antibodies directed against the cytokines (IL-1alpha, IL-1beta, IL-6, IL-8 and TNF-alpha) and the CAMs (intercellular adhesion molecule-1, ICAM-1 and vascular CAM-1, VCAM-1). RESULTS: The number of immunoreactive cells for IL-1alpha, IL-1beta, IL-6, IL-8, and TNF-alpha was increased significantly in patients with chronic sinusitis compared with normal controls. Immunoreactivity for ICAM-1 was also increased significantly in patients with chronic sinusitis compared with normal controls, whereas VCAM-1 is only minimally expressed or is absent in both groups. CONCLUSION: These findings indicate that bacterial and/or viral infection may induce functional and morphologic changes in the maxillary sinus mucosa in chronic sinusitis through enhanced generation of specific cytokines in conjunction with CAMs.

Adult↗

Acute profound sensorineural hearing loss as the initial manifestation of acute leukemia--report of a case.

This paper reports an unusual case in which acute lymphocytic leukemia presented acute profound sensorineural hearing loss as the initial manifestation of the disease. The patient is a 55-year-old woman who complained of left hearing loss of sudden onset. Pure tone audiometry revealed profound sensorineural hearing loss of the left ear at mid and low frequencies. The patient was tentatively diagnosed as idiopathic sudden deafness and admitted for the treatment, but her laboratory data indicated that she was at an advanced stage of leukemia. The patient's hearing loss did not improve subjectively until she deceased 1 year after the admission. The mechanism producing acute hearing loss in leukemic patients is reviewed and discussed, and the importance of differentiating possible underlying diseases before we diagnose idiopathic sudden deafness is stressed.

Acute Disease↗

Modification of glial-neuronal cell interactions prevents photoreceptor apoptosis during light-induced retinal degeneration.

Prolonged or high-intensity exposure to visible light leads to photoreceptor cell death. In this study, we demonstrate a novel pathway of light-induced photoreceptor apoptosis involving the low-affinity neurotrophin receptor p75 (p75NTR). Retinal degeneration upregulated both p75NTR and the high-affinity neurotrophin receptor TrkC in different parts of Müller glial cells. Exogenous neurotrophin-3 (NT-3) increased, but nerve growth factor (NGF) decreased basic fibroblast growth factor (bFGF) production in Müller cells, which can directly rescue photoreceptor apoptosis. Blockade of p75NTR prevented bFGF reduction and resulted in both structural and functional photoreceptor survival in vivo. Furthermore, the absence of p75NTR significantly prevented light-induced photoreceptor apoptosis. These observations implicate glial cells in the determination of neural cell survival, and suggest functional glial-neuronal cell interactions as new therapeutic targets for neurodegeneration.

Animals↗

Investigation on the formation and the determination of gamma-glutamyl-beta-alanylhistidine and related isopeptide in the macromolecular fraction of beef soup stock.

To confirm the formation of gamma-glutamyl-beta-alanylhistidine and related peptide, a model solution (amide-containing amino acids and carnosine) has been heated, and the products are investigated. Spectroscopical analysis indicates that the major product from asparagine and carnosine is beta-aspartyl-beta-alanylhistidine, and that from glutamine and carnosine is gamma-glutamyl-beta-alanylhistidine. Furthermore, to confirm the increase of the above peptides during the heating process of food, an HPLC method for the determination of these isopeptides in food protein is constructed. The isopeptides are liberated by proteolytic digestion and fractionated by solid-phase extraction using Toyopack IC-SP cartridges. The fraction containing the isopeptides is derivatized with phenylisothiocyanate (PITC) and separated and quantified by HPLC using an octadecyl-silica column. As a result of quantification, an increase of the gamma-glutamyl-beta-alanylhistidine isopeptide in the macromolecular fraction of heated beef soup stock solution has been observed. These results suggest that the formation of the isopeptide occurs in the heating of various foods containing carnosine.

Chromatography, High Pressure Liquid↗