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Biomedical subjects

H Tada

Publications and source records attributed to H Tada.

At least 91 records · Page 5Linked to original sources

Delapril versus manidipine in hypertensive therapy to halt the type-2-diabetes-mellitus-associated nephropathy.

Thirty-nine hypertensive patients with type 2 diabetes mellitus were followed under long-term treatment (mean, 20.7 months) with manidipine hydrochloride, a Ca antagonist, or delapril hydrochloride, an ACE inhibitor, at nine institutions. Both the treatments showed similar antihypertensive effects, although slight but significantly larger decreases were observed in systolic and mean blood pressures at months 12 and 24 in the patients treated with manidipine (P < 0.02). The urinary albumin excretion index (AEI) tended to increase throughout the study in both treatment groups, but no significant difference in AEI was observed between the two treatment groups at any time point. Overt albuminuria developed in four patients on manidipine but did not appear in any of the patients on delapril. The risk of progression to overt albuminuria was significantly different between manidipine and delapril groups (P = 0.011). No increase in serum creatinine (Cr) was observed with delapril. The average excretion indexes of tubular markers such as beta2-microglobulin, alpha1-microglobulin, and NAG tended to be higher in the patients on manidipine than in those on delapril. Taken in sum, these findings suggest that the ACE inhibitor delapril is more beneficial than the Ca antagonist manidipine in the treatment of diabetic renal diseases via mechanisms other than the blood pressure regulation, partly through their different effects on tubular function. In conclusion, delapril was significantly more effective than manidipine in inhibiting progression to overt albuminuria in hypertensive type 2 diabetes mellitus patients.

Adult↗

Demonstration of diastolic and presystolic Purkinje potentials as critical potentials in a macroreentry circuit of verapamil-sensitive idiopathic left ventricular tachycardia.

OBJECTIVES: The purpose of this study was to determine the relation of diastolic and presystolic potentials recorded during verapamil-sensitive idiopathic left ventricular tachycardia (ILVT) to reentry circuit. BACKGROUND: Successful ablation of verapamil-sensitive ILVT at the zone of slow conduction from which the diastolic potential is recorded has been reported. However, the relationship between the diastolic potential and the reentrant circuit remains a matter of debate. METHODS: Radiofrequency (RF) ablation was performed in 20 patients with verapamil-sensitive ILVT. After identifying the ventricular tachycardia (VT) exit site, we searched for the mid-diastolic potential (P1) during VT. Entrainment followed by RF current application was performed. If the mid-diastolic potential could not be detected, RF current was applied at the VT exit site showing the earliest ventricular activation with a single fused presystolic Purkinje potential (P2). RESULTS: In 15 of 20 patients, both P1 and P2 were recorded during VT from midseptal region. Entrainment pacing captured P1 orthodromically and reset the VT. The interval from stimulus to P1 was prolonged as the pacing rate was increased. Radiofrequency ablation was successfully performed at this site in all 15 patients. After successful ablation, P1 appeared after the QRS complex during sinus rhythm with the identical sequence to that during VT. In the remaining five patients, the diastolic potential could not be detected, and a single fused P2 was recorded only at the VT exit site. Successful ablation was performed at this site in all five patients. CONCLUSIONS: This study demonstrates that P1 and P2 are critical potentials in a circuit of verapamil-sensitive ILVT and suggests the presence of a macroreentry circuit involving the normal Purkinje system and the abnormal Purkinje tissue with decremental property and verapamil-sensitivity.

Adolescent↗

Detection of measles virus genome in bronchoalveolar lavage cells in a patient with measles pneumonia.

Measles is frequently complicated with pneumonia that could be fatal in numerous occasions. However, a prompt and precise diagnosis of measles is not easily made particularly in the early stage of the disease, or in immunocompromised individuals because of the lack of typical clinical features or the defect in antigen-specific antibody production. In the present paper, we describe a 27-yr-old male who developed fever, skin rash typical of measles, and diffuse pulmonary infiltrates associated with respiratory failure. Infection of lung cells with measles virus was proved by detection of viral genome ribonucleic acid within alveolar macrophages and lymphocytes recovered by bronchoalveolar lavage using reverse transcription-polymerase chain reaction amplification. These techniques may offer a useful tool to make the swift and precise diagnosis of measles pneumonia, thus allowing appropriate therapeutic approaches to the disease.

Adult↗

Expression of desmoglein I and plakoglobin in skin carcinomas.

Reduction or absence of cell-cell adhesion molecules has been reported in various carinomas and the abnormal expression of these molecules contributes to the invasive and metastatic behavior of malignant tumor cells. In epidermal keratinocytes, the main cell-cell adhesion systems are adherens junctions and desmosomes. Previous studies have shown that, in skin carcinomas, the decreased expression of E-cadherin, major constitutional glycoprotein of adherens junctions, is associated with the invasive and metastatic ability of the tumor cells. In the present study, we examined the expression of desmoglein I and plakoglobin, the constitutional components of desmosomes, in various skin carcinomas such as basal cell carcinoma (BCC), squamous cell carcinoma (SCC), extramammary Paget's disease and Bowen's disease by an immunofluorescence method. In normal human skin, desmoglein I and plakoglobin were strongly expressed in the intercellular space of the epidermis except for the basal cell layer. In BCC and SCC, the expression of desmoglein I and plakoglobin was markedly reduced or absent in tumor cells. In carcinoma in situ of Paget's disease, compared with the normal epidermal cells surrounding tumor cell nests, the expression of these molecules was reduced in tumor cells. In Paget's disease with dermal infiltration of tumor cells, the expression of these molecules was almost absent throughout the epidermis. In Bowen's disease, the expression of desmoglein I was reduced in the dumping cells and dyskeratotic cells. These results suggest that the expression of desmosomal cadherin is reduced or absent in human skin carcinomas, and that reduction of these molecules may also contribute to the invasiveness and metastasis of skin carcinomas.

Adult↗

Serum total bile acid level as a sensitive indicator of hepatic histological improvement in chronic hepatitis C patients responding to interferon treatment.

BACKGROUND AND METHODS: Serum total bile acid (TBA) levels are used clinically as a sensitive and reliable index of hepatobiliary diseases. In the present study, to assess the clinical usefulness of determining TBA in interferon (IFN)-treated patients, changes in liver function test values, including TBA and liver histology, were examined in 36 chronic hepatitis C patients for 3 years after a sustained response to IFN treatment. RESULTS: Alanine aminotransferase and gamma-glutamyl transpeptidase values significantly decreased during the period of IFN treatment compared to the same measures before IFN treatment. Albumin, cholinesterase, total cholesterol and platelet count values temporarily decreased during IFN treatment, then increased significantly and reached a plateau 6-12 months after the end of IFN treatment. The zinc sulphate turbidity test and TBA values began to decrease during IFN treatment and continued to decrease during the 3-year follow-up period. The histological activity index of the liver (Knodell's score) significantly decreased, whereas the staging score was unchanged 1 year after the end of IFN treatment. In patients who had a TBA value > 10 micromol/L before IFN treatment, a significant correlation was observed between the decrease of TBA and liver histology grading score. CONCLUSIONS: A decrease in serum TBA level reflected histological improvement in the liver more precisely than did changes in the other liver function test values following IFN therapy.

Adult↗

Convenient and efficient in vitro folding of disulfide-containing globular protein from crude bacterial inclusion bodies.

We investigated how the folding yield of disulfide-containing globular proteins having positive net charges from crude bacterial inclusion bodies was affected by additives in the folding buffer. In screening folding conditions for human ribonucleases and its derivative, we found that addition of salt (about 0.4 M) to a folding buffer increased the folding yield. This suggested that electrostatic interaction between polyanionic impurities such as nucleic acids and cationic unfolded protein led to the formation of aggregates under the low-salt conditions. Since inclusion bodies were found to contain nucleic acids regardless of the electrostatic nature of the expressed protein, the electrostatic interaction between phosphate moieties of nucleic acids and basic amino acid residues of a denatured protein may be large enough to cause aggregation, and therefore the addition of salt in a folding buffer may generally be useful for promotion of protein folding from crude inclusion bodies. We further systematically investigated additives such as glycerol, guanidium chloride, and urea that are known to act as chemical chaperons, and found that these additives, together with salt, synergistically improved folding yield. This study, suggesting that the addition of salt into the folding buffer is one of the crucial points to be considered, may pave the way for a systematic investigation of the folding conditions of disulfide-containing foreign proteins from crude bacterial inclusion bodies.

Bacterial Proteins↗

Stabilization of human RNase 1 by introduction of a disulfide bond between residues 4 and 118.

In order to stabilize human RNase 1 by introduction of an intramolecular cross-link, a mutant protein (4-118CL RNase 1), in which Arg4 and Val118 are replaced with cysteine residues and linked by a disulfide bond, was designed and expressed in Escherichia coli as inclusion bodies. The 4-118CL RNase 1 that refolded under redox conditions was a monomer without free SH groups and retained 11% of the activity of the wild-type recombinant RNase 1, indicating that the mutant enzyme was correctly folded with the formation of an additional disulfide bond between Cys4 and Cys118. From guanidium chloride denaturation experiments based on the assumption of a two-state transition for unfolding, it was demonstrated that the introduction of the present cross-link increased the thermodynamic stability of RNase 1 by 2.0 kcal/mol. This value was lower than that, 5.4 kcal/mol, theoretically calculated from the reduction of chain entropy of the unfolded state due to the introduction of the cross-link. These results suggest that the present cross-link also destabilized the folded state of RNase 1 by 3.4 kcal/mol. Along with the increase in the thermodynamic stability, the stability of RNase 1 against trypsin digestion was also significantly increased by the introduction of this cross-link. It is likely, although not proven, that stabilized human RNases are favorable for clinical use, because human RNase-based immunotoxins should have long half-lives as to proteolytic degradation after endocytosis.

Cysteine↗

Application of artificial dermis graft to correct a depression after tissue resection.

The authors present 7 cases of artificial dermis implantation to correct a depression after tissue resection. Four of the seven cases resulted from resection of a malignant tumor (N = 3) and from a benign subcutaneous tumor (N = 1). The other 3 cases were the result of temporal muscle harvest to reconstruct facial palsy. In 1 patient a mild degree of bone deformity also existed. The pieces of artificial dermis employed varied from 35 x 40 to 40 x 80 mm in size. In 5 patients two sheets were implanted, and in 2 patients three sheets were implanted. In 2 patients the dermis sheets were covered by a pedicled temporal fascial flap with a free split-thickness skin graft because whole skin was resected as a result of a malignant skin tumor. There was no postoperative infection or allergic reaction in any of the patients. In all cases there was no postoperative contracture, and the implanted area was soft. An adequate or acceptable thickness of subcutaneous tissue was obtained. Artificial dermis may be a useful option as implantation material to correct a depression after tissue resection, especially for wide and comparatively shallow depressions.

Aged↗

An evaluation of hard palate mucosa graft as a lining material in alar reconstruction: a 7-year experience applied to the full-thickness alar defect.

The authors present their experience with 25 hard palate mucosa grafts used as lining material in the reconstruction of full-thickness alar defects. Good "take" was obtained in 22 grafts; the other three grafts incurred necrosis of the overriding skin flaps and postoperative infection. Degree of shrinkage was 11 to 15 percent of grafted size in patients with the type of defect that did not include the alar margin; shrinkage was 26 to 35 percent in patients with the type that included more than 50 percent of the alar margin. In all patients who had a good graft take, the nasal cavities were maintained and there was no nasal obstruction or collapsing during strong breathing. The healing time of the palate donor site varied from 7 days to 5 weeks, depending on the size of the defect. No patients experienced any symptoms at the donor site after healing. The authors concluded that hard palate mucosa can be considered a useful material in alar reconstruction because of the ease in graft harvesting and its support features. When the defect is large enough to involve the total unilateral ala nasi, even though the degree of postoperative shrinkage is comparatively high, hard palate mucosa may be the most suitable material to ensure good take of the graft and less possibility of donor-site morbidity.

Adult↗

ST segment and T wave alternans in a patient with Brugada syndrome.

We describe a patient with Brugada syndrome in whom J point and ST-segment elevation in leads V1 and V2 were augmented by atrial pacing and intravenous administration of propranolol or cibenzoline. Significant T wave alternans with a 2:1 appearance of terminal negative T wave was observed in the absence and presence of atrial pacing after the administration of cibenzoline. The cellular mechanism responsible for T wave alternans, beat-to-beat appearance of terminal negative T wave and augmented J point and ST-segment elevation is discussed.

Bundle-Branch Block↗

Changes in cytokine production during and after normal pregnancy.

PROBLEM: The systemic T helper 1/T helper 2 (Th1/Th2) cytokine balance during normal human pregnancy is controversial, and observations about the balance in the postpartum period have only been reported for up to 3 months. METHOD: Whole-blood, from 83 healthy pregnant women, 80 healthy postpartum women, and 31 healthy non-pregnant women was stimulated with phorbol 12-myristate 13-acetate (PMA) and ionomycin, and the levels of cytokines in the supernatant were measured by enzyme-linked immunosorbent assay (ELISA). RESULTS: The production of all measured cytokines decreased during pregnancy, especially in the second trimester. After delivery, interferon-gamma (IFN-gamma) and interleukin-2 (IL-2) increased from 2 to 11 months postpartum, and IL-4 increased from 6 to 11 months postpartum. CONCLUSIONS: These data indicate that 1) decreases in production of both Th1-and Th2-type cytokines during pregnancy may be related to the pregnancy-induced amelioration of autoimmune diseases: 2) increases in production of both Th1- and Th2-type cytokines in the postpartum period may be related to the postpartum aggravation of autoimmune diseases.

Adult↗

CD13/aminopeptidase N, a novel chemoattractant for T lymphocytes in pulmonary sarcoidosis.

CD13/aminopeptidase N (E.C.3.4.11.2) is an ectoenzyme located in the outer membrane of a variety of cells. Because aminopeptidase expression was shown to be upregulated by a Th1-related cytokine, IFN-gamma, we examined here the significance of CD13/aminopeptidase N in pulmonary sarcoidosis. The activity of aminopeptidase in bronchoalveolar lavage fluid (BALF) was significantly higher in patients with sarcoidosis than in normal volunteers (NV) and control patients (CP). The activity significantly correlated with lymphocyte percentages and the ratio of CD4+ to CD8+ T lymphocytes in the BALF, and was higher in patients with sarcoidosis with parenchymal involvement than in those without the involvement. CD13/aminopeptidase N protein, which has a molecular mass of approximately 150 kD, was detectable in alveolar macrophages (AM) from patients with sarcoidosis at higher levels than in those from NV. CD13/aminopeptidase N induced in vitro chemotactic migration of human lymphocytes in a concentration range of 10(-)(5) to 10(-)(1) U/ml. The chemotactic activity was greater for CD4+ T lymphocytes than for CD8+ T lymphocytes. The enzymatic activity of CD13/aminopeptidase N was responsible for the chemotactic activity because bestatin, an inhibitor of CD13/aminopeptidase N, abolished the chemotactic activity. Higher chemotactic activity for lymphocytes was detected in the BALF from patients with sarcoidosis than in that from NV, and the activity was significantly decreased by treatment with bestatin. This study indicates that CD13/ aminopeptidase N expressed in AM may have a role in T-lymphocyte involvement in the sarcoid lung and the pathogenesis of alveolitis in this disorder.

Adult↗

Coronary vascular K+ATP channels contribute to the maintenance of myocardial perfusion in dogs with pacing-induced heart failure.

The functional role of coronary vascular ATP-sensitive potassium (K+ATP) channels in the regulation of coronary blood flow (CBF) has not been determined in chronic heart failure (CHF). To test the hypothesis that K+ATP channels contribute to myocardial perfusion in HF, we examined the effects of intracoronary infusion of glibenclamide, an inhibitor of K+ATP channels, on basal CBF in control and CHF dogs. CHF was produced in mongrel dogs by pacing the right ventricle for 4 weeks. Under anesthesia, CBF in the left anterior descending coronary artery, other hemodynamic and metabolic parameters, or regional myocardial blood flow were measured. Basal CBF was less in CHF dogs than in controls. Glibenclamide at the graded doses (5, 15 and 50 microg x kg(-1) x min(-1) decreased CBF in both control and CHF dogs. The percentage decrease in CBF with glibenclamide at 50 microg x kg(-1) x min(-1) was greater (p<0.01) in CHF dogs than in controls. The greater decrease in CBF with glibenclamide at 50microg x kg(-1) x min(-1) was associated with myocardial ischemia. Glibenclamide decreased myocardial blood flow in each sublayer of the myocardium in the 2 groups. These results suggest that the basal activity of coronary vascular K+ATP channels is increased in CHF dogs but not in controls. This may contribute to the maintenance of myocardial perfusion in CHF.

Adenosine Triphosphate↗

Implantation of ultraflex nitinol stents in malignant tracheobronchial stenoses.

STUDY OBJECTIVE: To assess the uncovered Ultraflex nitinol stent (Boston Scientific; Natick, MA) for its efficacy and safety. DESIGN, SETTING, AND PATIENTS: Between October 1997 and October 1998, we carried out a prospective multicenter study at six hospitals in Japan. Fifty-four Ultraflex stents were inserted in 34 patients with inoperable malignant airway stenosis using a flexible and/or a rigid bronchoscope under fluoroscopic and endoscopic visualization. MEASUREMENTS AND RESULTS: Clinical, endoscopic examination, and pulmonary function on days 1, 30, and 60 after stent implantation showed improvement. In 19 patients (56%), stent implantation was performed as an emergency procedure because of life-threatening tracheobronchial obstruction. Immediate relief of dyspnea was achieved in 82% of the patients. The dyspnea index improved significantly after implantation (before vs. days 1, 30, and 60; p<0.001). Significant improvements were observed in obstruction of airway diameter (81+/-15% before vs. 14+/-17% on day 1, 12+/-12% on day 30, and 22+/-28% on day 60; p<0.001). Vital capacity (VC), FEV(1), and peak expiratory flow (PEF) increased significantly after stent implantation: before vs immediately after VC (p<0.01), FEV(1) (p<0.001), and PEF (p<0.05). The main complications were tumor ingrowth (24%) and tumor overgrowth (21%). After coagulation with an Nd-YAG laser or argon plasma coagulation, mechanical coring out using the bevel of a rigid bronchoscope was necessary in patients showing tumor ingrowth or overgrowth. Removal and reposition were possible in case of misplacement. There were no problems with migration and retained secretions. The median survival time of patients was 3 months. The 1-year survival rate was 25.4%. CONCLUSIONS: In this study of the Ultraflex nitinol stent, we have demonstrated that patients were relieved from dyspnea, which contributed to improved quality of life, with minimal complications. This stent can be used safely, even in the subglottic region. Owing to its excellent flexibility and biocompatibility, the stent is also indicated in certain complicated situations, eg, narrow stenosis, hourglass stenosis, curvilinear stenosis, bilateral mainstem bronchial stenoses, and long stenosis of varying diameters.

Adult↗

Preoperative diagnosis of thyroid carcinomas by aspiration biopsy-reverse transcription-polymerase chain reaction (ABRP): a report of two cases.

A preoperative molecular-based diagnostic technique for thyroid papillary and anaplastic carcinomas was recently developed to detect oncofetal fibronectin (onfFN) messenger RNA (mRNA) in fine needle aspiration biopsy (FNAB) by means of reverse transcription-polymerase chain reaction (RT-PCR). We report two cases of thyroid tumors, in which cytological diagnosis was not successful but in which RT-PCR analysis provided information that helped to identify the biological features of the tumors. One case could not be diagnosed by aspiration biopsy cytology (ABC) because of poor fixation; however, RT-PCR did detect the expression of onfFN mRNA, which suggested the existence of papillary carcinoma cells. After surgery, this tumor was diagnosed as a papillary carcinoma by histological examination. The other case was diagnosed as a papillary carcinoma by ABC, but onfFN mRNA was not detected in the FNAB by RT-PCR. The neoplasm was diagnosed as a follicular tumor by histological examination. These cases suggest the benefits of combining both genetic and cytological approaches to the examination of FNAB.

Adult↗