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Biomedical subjects

M Matsuda

Publications and source records attributed to M Matsuda.

At least 937 records · Page 52Linked to original sources

Electrophoretic determination of fructose 6-phosphate,2-kinase.

An electrophoretic determination of fructose 6-phosphate,2-kinase activity has been devised. The enzymes partially purified from bovine liver and heart were subjected to polyacrylamide gel electrophoresis and the production of fructose 2,6-bisphosphate, coupled to the activation of potato PPi:phosphofructokinase, was detected as the dark band due to the disappearance of the fluorescence evoked by NADH consumption. The enzyme from bovine heart showed slower electrophoretic mobility than that from bovine liver, strongly suggesting the possibility that they may be distinct enzyme forms. Rat liver enzyme also gave a mobility different from that of both bovine liver and heart enzymes. Our present procedure will provide a new tool for understanding fructose-6-phosphate,2-kinase/fructose 2,6-bisphosphatase system in various tissues.

Animals↗

Increased tubulin messenger RNA in the frog retina after optic nerve transection.

The optic nerve of the bullfrog (Rana catesbeiana) was transected and the regeneration process was investigated. The nerve regeneration was confirmed by observing the extension of the axon and by examining the recovery of axonal transport. Following optic nerve transection, the rapid and transient increase of messenger RNA of alpha-tubulin gene was observed in the retina, but no specific change of actin messenger RNA was observed.

Animals↗

Aldose reductase inhibitor (CT-112) eyedrops for diabetic corneal epitheliopathy.

We treated two diabetic patients with corneal epithelial disorder that resisted conventional medical therapy with topical CT-112 (5-[3-ethoxy-4-pentyloxyphenyl]-2,4-thiazolidinedione), a newly synthesized aldose reductase inhibitor. One patient had developed recurrent corneal erosion after vitrectomy and the other had spontaneously developed superficial punctate keratopathy. The corneal lesion in each patient responded to topical CT-112 in two to four weeks and was almost cleared within two months. A similar corneal lesion recurred in both patients soon after CT-112 was discontinued, but it disappeared again when the drug was resumed.

Aged↗

Long-term corneal endothelial changes after intraocular lens implantation.

We studied the morphologic characteristics of the corneal endothelium in a series of patients who had undergone phacoemulsification with intraocular lens implantation performed by one surgeon. Specular microscopy and computer-assisted morphometry were performed preoperatively and three years after surgery. Nineteen eyes that received posterior chamber lenses with intracapsular fixation had a mean endothelial cell loss of 18.1%, without any significant change in cell size (polymegethism) or shape variability (pleomorphism). Implantation of anterior chamber lenses with the posterior capsule left intact (18 eyes) caused a similar degree of cell loss (23.5%) but caused marked polymegethism and pleomorphism of the cells. Endothelial cell loss (28.5%) and morphologic changes were greatest in five eyes that received anterior chamber lenses because of a rupture of the posterior capsule.

Cataract Extraction↗

Conformation of antithrombin III with defective biological functions derived from a thrombophilic patient.

Antithrombin III (AT III) with defective biological functions and altered antigenicity has been found in a thrombophilic patient. Circular dichroism (CD) spectra of antithrombin III purified from the patient's plasma were measured in near and far-ultraviolet (UV) wavelength regions. The far-UV CD spectrum of the patient's AT III was similar at room temperature to that of normal AT III derived from healthy adult males. Mean residue ellipticity at 221 nm of the patient's AT III, however, decreased its magnitude by 6% gradually as temperature increased up to 74 degrees C, whereas that of the normal AT III reduced its magnitude sharply at around 63-64 degrees C and by 18%. The near-UV CD spectrum of patient's AT III was different from that of normal AT III. These results indicate that the secondary structure of patient's AT III is similar to that of normal AT III at room temperature, while local conformation of aromatic amino acid residues in the abnormal protein is different from that in the normal one and that the secondary structure of the patient's AT III is heat-stable, while that of the normal one is heat-labile.

Antithrombin III↗

Interaction of tissue-type plasminogen activator and plasminogen activator inhibitor 1 on the surface of endothelial cells.

The site of the reaction between plasminogen activators and plasminogen activator inhibitor 1 (PAI-1) was investigated in cultures of human umbilical vein endothelial cells. In conditioned medium from endothelial cells, two forms of a plasminogen activator-specific inhibitor can be demonstrated: an active form that readily binds to and inhibits plasminogen activators and an immunologically related quiescent form which has no anti-activator activity but which can be activated by denaturation. In conditioned medium, only a few percent of PAI-1 is the active form. However, the addition of increasing concentrations of tissue-type plasminogen activator (t-PA) or urokinase to confluent endothelial cells produced a saturable (3.0 pmol/5 x 10(5) cells), dose-dependent increase of the activator-PAI-1 complex in the conditioned medium even in the presence of actinomycin D or cycloheximide. This resulted also in a dose-dependent decrease of the residual PAI activity measured by reverse fibrin autography both in the conditioned medium and cell extracts. Short-time exposure of endothelial cells to a large amount of t-PA caused almost complete depletion of all cell-associated PAI activity. Although there was no detectable PAI activity even after activation of PAI by denaturants or antigen in the culture medium at 4 degrees C without the addition of t-PA, the addition of t-PA at 4 degrees C not only resulted in the formation of 70% of the amount of the t-PA.PAI complex in conditioned medium at 37 degrees C, but also induced PAI-1 antigen in a time and dose-dependent manner in the conditioned medium. Moreover, 125I-labeled t-PA immobilized on Sepharose added directly to endothelial cells formed a complex with PAI-1 in a dose-dependent manner. On the other hand, no detectable complex was formed with PAI-1 when Sepharose-immobilized 125I-labeled t-PA was added to endothelial cells under conditions in which the added t-PA could not contact the cells directly but other proteins could pass freely by the use of a Transwell. All these results suggest that a "storage pool" on the surface of endothelial cells or the extracellular matrix produced by endothelial cells contains almost all the active PAI-1, and reaction between PA and PAI-1 mainly occurs on the endothelial cell membranes, resulting in a decrease of the conversion of active PAI-1 to the quiescent form.

Dose-Response Relationship, Drug↗

Preparation and characterization of monoclonal antibodies against the human thrombin-antithrombin III complex.

Monoclonal antibodies were raised against human thrombin-antithrombin III complex by a hybridoma technique. Among them, five monoclonal antibodies, designated as JITAT-4, -14, -16, -17 and -19, were found to react with thrombin-antithrombin III, but not with its nascent components, alpha-thrombin or antithrombin III. Their respective immunoglobulin classes are IgG1 for JITAT-16 and -19, and IgG2a for JITAT-4, -14 and -17. Besides the thrombin-antithrombin III complex, they all bound to the Factor Xa-antithrombin III complex and the active-site-cleaved two-chain antithrombin III as well. Moreover, the reactivity of these two antibodies to the neoantigens was not affected by heparin, suggesting that their epitopes are independent of heparin-induced conformational changes of antithrombin III. Two of them, JITAT-16 and -17, were categorized as high-affinity antibodies to thrombin-antithrombin III complex, the dissociation constants being 6.7 nM and 4.8 nM, respectively. However, they do not share antigenic determinants. These monoclonal antibodies may allow us to explore more precisely the reaction between antithrombin III and thrombin or its related enzymes.

Antibodies, Monoclonal↗

Corneal endothelial changes associated with aphakic extended contact lens wear.

Wide-field specular microscopy and computer-assisted morphometry were performed on 20 aphakic eyes in 16 patients who had worn a high-water content hydrogel contact lens on an extended wear basis for at least 12 months (mean, 28 months) following intracapsular cataract extraction. When compared with 22 non-lens-wearing aphakic eyes matched for age and postoperative period, the endothelial cell changes in the above patients included a significantly higher coefficient of variation in cell area (polymegathism) and a marked reduction in the frequency of hexagonal cells (pleomorphism) without any significant difference in cell density. Although the clinical significance of these endothelial changes remains unclear, they may indicate hypoxic stress to the corneal endothelium or be an early sign of ongoing cell loss.

Aged↗

Mitral valve motion during diastole in patients with complete heart block: relation of pressure gradients between left atrium and left ventricle.

We analyzed the high-fidelity left atrial and left ventricular pressures and the echocardiograms of the mitral valve, left atrium, and left ventricle in patients with complete heart block. During left ventricular diastole, the mitral valve opened, and no pressure gradient was observed between the left atrium and the left ventricle before the left atrial contraction. After the left atrial contraction, the mitral valve closed with persistent higher left ventricular than left atrial pressure. These findings indicated that during the left ventricular diastole in patients with complete heart block, the mitral valve closed after the left atrial contraction, which appeared to be maintained by the pressure gradient between the left ventricle and the left atrium.

Aged↗

Serum proteins enhance aggregate formation of dissociated fetal rat brain cells in an aggregating culture.

Dissociated fetal rat brain cells (Day 14.5 of gestation) reaggregated into small cell clusters and formed large aggregates in a medium supplemented with serum or dialyzed serum in an aggregating culture. In contrast, only small aggregates were produced in a serum-free medium. The present results indicated that albumin, fetuin, transferrin, and alpha 1-antitrypsin enhanced the aggregate formation. Small aggregates produced in a serum-free medium elongated neurites when they were cultured within a collagen gel matrix. Total DNA per flask was almost the same in small and large aggregates. Thus, these serum proteins may well play an important role in the adhesion of small cell clusters and cause the formation of large aggregates in this short-term aggregating culture.

Animals↗

Effects of a new Ca2+ antagonist, KB-2796, on the regional cerebral blood flow and somatosensory evoked potentials in the ischemic brain in cats.

Effects of a new Ca2+ antagonist, 1-[bis(4-fluorophenyl) methyl]-4-(2,3,4-trimethoxybenzyl) piperazine dihydrochloride (KB-2796), on the regional cerebral blood flow (rCBF) and somatosensory evoked potentials (SEPs) were investigated using a model of focal cerebral ischemia in cats. In experiment 1, an occlusion of the middle cerebral artery for 4 hours persistently reduced the ipsilateral rCBF in both the control and the KB-2796-treated groups. However, the flow reduction was much milder in the treatment group than in the control group. Amplitudes of the SEPs diminished in both groups but the rate of deterioration was much slower in the treatment group than in the control group. In experiment 2, an occlusion of the middle cerebral artery for 1 hour was followed by reperfusion for 3 hours. The ipsilateral rCBF decreased during occlusion in both the control and the treatment groups. In the control group, postischemic hyperperfusion was seen in the ectosylvian gyrus after reperfusion, whereas the ipsilateral rCBF recovered rapidly to the control values without showing a phase of hyperperfusion in the treatment group. The rate of recovery of the SEPs was also much more rapid in the treatment group.

Animals↗

Acute cytogenetic effects of potassium bromate on rat bone marrow cells in vivo.

The acute cytogenetic effects of potassium bromate (KBrO3) on rat bone marrow cells in vivo were studied. The incidence of chromosome aberrations in bone marrow cells increased rapidly, reaching a maximum level 12 h after intraperitoneal injection and decreased within 24 h. Dose-response relationships were obtained for both intraperitoneal and oral administrations.

Administration, Oral↗

Surgical repair of varicocele at puberty: preventive treatment for fertility improvement.

In 40 pubertal boys with a varicocele a comparative followup study was performed to evaluate the efficacy of surgical correction of the varicocele in this age group in regard to improvement of fertility after completion of sexual maturation. The varicocele was corrected surgically in 24 patients and it was left uncorrected in 16. Testicular atrophy was noted in all cases at the initial visit and after followup. Of the 24 corrected patients 16 had atrophy of at least 1 testis before surgical treatment, whereas only 7 demonstrated atrophy after followup. Of the 16 uncorrected patients testicular atrophy was noted in 8 at the initial visit but 12 had atrophy after followup. Semen examination of 23 patients who had completed sexual maturation demonstrated a higher quality of routine seminal parameters, for example sperm density, sperm motility and percentage of morphologically normal spermatozoa, in the corrected group than in the uncorrected group.

Adolescent↗

Human immunodeficiency virus type 1 has an additional coding sequence in the central region of the genome.

Eight coding regions designated gag, pol, env, sor, R, tat, art/trs, and 3' orf have been identified in the genome of the human immunodeficiency virus type 1 (HIV-1). Several other open reading frames have the potential to encode additional viral proteins. In this study, we show that HIV-1 has another coding sequence whose product is expressed during natural infection. Unlike antibody to other HIV-1 proteins, the prevalence of antibody to the product encoded by this region is elevated in patients with acquired immune deficiency syndrome (AIDS). Because no analogous coding region has been identified in HIV-2, the antibody to the product of this coding region may serve as a marker to distinguish infection with HIV-1 from infection with HIV-2.

Acquired Immunodeficiency Syndrome↗

Relationship between cigarette smoking and histologic type of lung cancer, with special reference to sex difference.

In order to clarify sex differences associated with the relationship between smoking and each histologic type of lung cancer, the smoking histories of 2,083 lung cancer patients (1,660 men and 423 women) diagnosed at the Center for Adult Diseases, Osaka, from 1965 to 1983 were analyzed. The rates expected of smokers among these cases were calculated from the sex and age specific rates of smokers in the general population, reported annually by the Japan Tobacco and Salt Public Corporation. The odds ratios for smoking were estimated to be 5.2, 3.1, 6.9, and 4.1 in men for squamous cell carcinoma, adenocarcinoma, small cell carcinoma and large cell carcinoma, and 7.2, 1.8, 14.4 and 3.8 in women respectively. Significant differences in the odds ratios for each histologic type between men and women were observed only for adenocarcinoma. In squamous cell carcinomas, the odds ratios were estimated by dividing them into two groups according to location. No difference was found between men and women in this respect.

Adenocarcinoma↗

LH-RH agonist, Zoladex (Goserelin), depot formulation in the treatment of prostatic cancer. Randomized dose-finding trial in Japan.

Ninety patients with advanced prostatic cancer (15 with stage B, 23 with stage C, and 52 with stage D) were randomized to receive 0.9, 1.8, or 3.6 mg, respectively, of Zoladex depot subcutaneous injection every 28 days for 12 weeks. The serum levels of LH, FSH, and testosterone were elevated after the first injection, and followed by a significant decrease. The suppression of testosterone levels in the blood to castrate levels was observed in all patients except two treated with 0.9 mg. Objective response (CR and PR) was seen in 63.6% (0.9 mg), 47.8% (1.8 mg), and 68% (3.6 mg) of patients according to the Japanese Prostatic Group Criteria. Subjective improvement (performance status, analgesic consumption) was also observed in 75-88% of patients but without a statistically significant difference between each dose group. Only minor adverse effects were found during the treatments. The drug was detected dose dependently in the blood by radioimmunoassay. These results suggest that endocrine therapy with Zoladex depot in doses of 3.6 mg subcutaneously every 4 weeks is a useful alternative to surgical castration in patients with prostatic cancer.

Aged↗