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Biomedical subjects

T Terada

Publications and source records attributed to T Terada.

At least 181 records · Page 10Linked to original sources

Marinesco-Sjögren syndrome associated with acute myeloblastic leukemia.

Marinesco-Sjögren syndrome is a rare autosomal recessive disorder characterized by cerebellar atrophy, ataxia, cataracts, short stature and varying degrees of mental retardation. A high incidence of malignant disease associated with this syndrome has not so far been reported. We report the case of a 6-year-old girl affected with Marinesco-Sjögren syndrome, who developed acute myeloblastic leukemia (AML, M2), and whose karyotype was 46,XX,t(8;21),(q22;q22) in bone marrow blasts. This is the first report of Marinesco-Sjögren syndrome associated with malignant disorders.

Brain↗

Recognition of beta-lactam antibiotics by rat peptide transporters, PEPT1 and PEPT2, in LLC-PK1 cells.

PEPT1 and PEPT2 are H(+)-coupled peptide transporters expressed preferentially in the intestine and kidney, respectively, which mediate uphill transport of oligopeptides and peptide-like drugs such as beta-lactam antibiotics. In the present study, we have compared the recognition of beta-lactam antibiotics by LLC-PK1 cells stably transfected with PEPT1 or PEPT2 cDNA. Cyclacillin (aminopenicillin) and ceftibuten (anionic cephalosporin without an alpha-amino group) showed potent inhibitory effects on the glycylsarcosine uptake in the PEPT1-expressing cells. Other beta-lactams, such as cephalexin, cefadroxil, and cephradine (aminocephalosporins), inhibited modestly the PEPT1-mediated glycylsarcosine uptake. Except for ceftibuten, these beta-lactams showed much more potent inhibitions on the glycylsarcosine uptake via PEPT2 than via PEPT1. Comparison of the inhibition constant (Ki) values between cefadroxil and cephalexin suggested that the hydroxyl group at the NH2-terminal phenyl ring increased affinity for both PEPT1 and PEPT2. It is concluded that PEPT2 has a much higher affinity for beta-lactam antibiotics having an alpha-amino group than PEPT1 and that substituents at the NH2-terminal side chain of these drugs are involved in the recognition by both peptide transporters.

Animals↗

Purification and some properties of lignostilbene-alpha, beta-dioxygenase isozyme IV from Pseudomonas paucimobilis TMY1009.

Lignostilbene-alpha, beta-dioxygenase isozyme IV was purified from ultrasonic extracts of Pseudomonas paucimobilis TMY1009 through four steps of column chromatography. The fraction obtained gave a single band on SDS-PAGE and a single peak on reversed-phase HPLC and DEAE-HPLC. The specific activity and Km of purified isozyme IV were 110 mu kat/g and 4.2 microM for 4.4'-dihydroxy-3,3'-dimethoxystilbene, 150 mu kat/g and 3.3 microM for 4,2'-dihydroxy-3,3'-dimethoxy-5'-(2"-carboxyvinyl)stilbene. The molecular mass of intact isozyme IV was estimated to be 94 kDa by gel permeation chromatography, and that of its subunits was 52 kDa by SDS-PAGE under denaturing conditions. The N-terminal amino acid sequence of isozyme IV differed slightly from that of other isozymes. Isozyme IV seemed to be composed of two identical subunits, gamma gamma.

Amino Acid Sequence↗

Cytotoxicity of cholestane 3 beta,5 alpha,6 beta-triol on cultured intestinal epithelial crypt cells (IEC-6).

The effects of cholestane 3 beta,5 alpha,6 beta-triol on intestinal epithelial crypt cells were investigated using the IEC-6 cell line. Cholestane 3 beta,5 alpha,6 beta-triol decreased SH groups (glutathione and protein SH) in the cell, and showed cytotoxicity in a time-dependent manner. Although the concentration of cholestane 3 beta,5 alpha,6 beta-triol used in this study (100 microM) was very high compared with that in plasma of experimental animals, cholestane 3 beta,5 alpha,6 beta-triol did not show any cytotoxicity on IEC-6 cells without fetal calf serum (FCS). The level of cytotoxicity was dependent upon the concentration of FCS in the culture medium. Unknown components in FSC (not VLDL or LDL) were suggested to be associated with the cytotoxicity of cholestane 3 beta,5 alpha,6 beta-triol. Moreover, the fact that even heat-treated FCS (100 degrees C for 30 min) still mediated the cytotoxicity suggested the participation of non-protein components.

Animals↗

Normal and abnormal development of the human intrahepatic biliary system: a review.

Morphology and immunohistochemical features of the developmental process of the human intrahepatic biliary system (IBS) are reviewed. Human IBS arises from the ductal plate, a double-layered cylindrical structure located at the interface between portal mesenchyme and primitive hepatocytes. The ductal plate first appears from primitive hepatocytes (hepatoblasts) around 8 gestational weeks (GW), and its formation proceeds from the hepatic hilum to the periphery. The ductal plate gradually undergoes remodeling from 12 GW; some parts of the ductal plate disappear and other parts migrate into the portal mesenchyme. Around 20 GW, the migrated duct cells transform into immature bile ducts and peribiliary glands. Some immature peribiliary glands transform into pancreatic acinar cells around postnatal 3 months. The immature biliary elements express cytokeratins no. 7, 8, 18 and 19. Several growth factors (TGF-alpha, HGF) and their receptors (EGFR, MET, ERBB2) were expressed in the primitive IBS cells. Some extracellular matrix proteins including type IV collagen, laminin and tenascin are expressed in the mesenchyme around the primitive IBS. During IBS remodeling, apoptosis and cell proliferation occur with appropriate expression of apoptosis-related proteins (bcl-2, Fas, c-myc, Lewis(y)). Some pancreatic digestive enzymes (alpha-amylase, trypsinogen, lipase), cathepsin B, and matrix metalloproteinases (MMP-1, 2, 3, 9) and their inhibitors (TIMP-1, 2) are expressed in the remodeling IBS cells. Glycoconjugate residues of glycoproteins gradually appear during IBS development. The appropriate expression of these immunophenotypes may play an important role in the normal development of IBS.

Animals↗

Iatrogenic arteriovenous fistula of the middle meningeal artery caused during embolization for meningioma--case report.

A 73-year-old female developed middle meningeal arteriovenous fistula during embolization of a falx meningioma. The cause of this complication was thought to be perforation by the guide wire during catheterization at the sharp bend in the sphenoidal portion of the middle meningeal artery. Embolization of the fistula and the feeding artery to the meningioma with polyvinyl alcohol particles 250-355 microns size resulted in complete obliteration of the fistula. Computed tomography showed no epidural or subdural hematoma. Introduction of the microcatheter beyond the sharp bend in the middle meningeal artery should not be attempted to avoid the possibility of iatrogenic middle meningeal arteriovenous fistula.

Aged↗

[A patient with epilepsy manifesting reversible memory dysfunction--a neuropsychological, electroencephalographical and radiological study].

A 49-year-old man was admitted to our hospital because of epileptic seizures and memory dysfunction. He had been experiencing seizures several times a day since the age of 43 years. Despite antiepileptic drug therapy (sodium valproate [VPA] and clonazepam [CZP], he suffered from frequent complex partial seizures originating in the temporal lobe, and he had a memory disturbance since age 47. When carbamazepine (CBZ) was substituted for VPA and CZP, the epileptic seizures stopped and the memory disturbance improved. Noninvasive regional cerebral blood flow (rCBF) measurements using 99mTc-HMPAO-SPECT imaging were performed twice. The initial measurements on admission showed overall decreased rCBP that was more prominent in the cerebral cortex than in the subcortical nuclei. A follow-up SPECT examination after clinical improvement revealed a marked overall increase in rCBF, especially in the cerebral cortex. The SPECT findings suggest that the memory disturbance in this patient may have been associated with the overall cerebral blood hypoperfusion. This overall hypoperfusion can be attributed to the frequent complex partial seizures and/or the adverse effect of VPA and CZP. SPECT can provide important information suggesting the pathogenesis of memory disturbance associated with epilepsy.

Anticonvulsants↗

[Spontaneous intracranial hypotension with severe headache and typical neuroradiological findings: report of two cases].

Intracranial hypotension causes the postural headache that sometimes follows lumbar puncture. When postural headache and associated symptoms occur after lumbar puncture, the diagnosis is usually obvious. However, similar symptoms may occur after minor trauma or without an obvious precipitating cause (spontaneous intracranial hypotension: SIH). SIH is rare, but is now increasingly recognized as a cause of postural headache. We encountered two cases of SIH showing typical neuroradiological findings. Case 1 is a 47-year-old man who was admitted with severe frontalgia. CT scan revealed vague visualization of bilateral Sylvian fissures and slit ventricles. Spinal fluid pressure was 6cm H2O in the lateral recumbent position. Cerebrospinal fluid (CSF) showed slight lymphocytic pleocytosis. We treated him as having viral meningitis. His headache improved gradually and he was discharged 2 weeks later with slight occipitalgia. One week after discharge, he complained of severe headache again and plain CT showed bilateral subdural hematoma. The subdural hematoma in both sides was evacuated and his headache improved after the operation. Follow-up CT scans two months later showed normalization of ventricle size and cisterns. Case 2 is a 52-year-old woman who was admitted with severe occipitalgia. CT scan on admission showed slit ventricles and the disappearance of the suprasellar cistern and the Sylvian fissure. Spinal fluid pressure was 3cm H2O. Gd-enhanced MRI showed remarkable meningeal enhancement and effacement of the optic chiasm suggesting brain sagging. Her headache improved 2 weeks later after strict bed rest and oral pain relief drugs. The follow-up MRI showed disappearance of abnormal meningeal enhancement and normalization of optic chiasma effacement. SIH is one of the important differential diagnoses of patients complaining of postural headache. Meningeal enhancement of gadolinium-enhanced MRI is an important finding to diagnose SIH. We have to consider SIH when diagnosing postural headache.

Brain↗

Characterization of stably transfected kidney epithelial cell line expressing rat H+/peptide cotransporter PEPT1: localization of PEPT1 and transport of beta-lactam antibiotics.

We established stably transfected LLC-PK1 cells expressing the rat H+/peptide cotransporter PEPT1 (designated LLC-rPEPT1) and examined membrane localization and uptake by rat PEPT1 of oral beta-lactam antibiotics. The LLC-rPEPT1 cells expressed a novel PEPT1 protein with an apparent molecular mass of 75 kdaltons, which was found in rat intestinal membranes. The cell surface biotinylation of LLC-rPEPT1 cell monolayers grown on membrane filters showed that PEPT1 was localized predominantly on the apical membranes and, to a lesser extent, on the basolateral membranes. The amount of [14C]glycylsarcosine uptake in LLC-rPEPT1 cell monolayers was 3-fold greater from the apical, than from the basolateral side, which suggested that rat PEPT1 expressed on both membranes was functionally active. LLC-rPEPT1 cells grown on plastic dishes transported differently charged oral cephalosporins such as ceftibuten (divalent anion lacking an alpha-amino group) and cephradine (zwitterion with an alpha-amino group) in the presence of an inward H+ gradient, whereas those transfected with the vector alone did not have transport activity. Kinetic analysis revealed that the LLC-rPEPT1 cells had much higher affinity for ceftibuten than for cephradine. Di- and tripeptides and bestatin, a dipeptide-like antineoplastic drug, potently inhibited the uptake of these cephalosporins. These results suggest that the LLC-rPEPT1 cells serve as a useful model with which to analyze the mechanisms involved in membrane targeting and substrate recognition by rat PEPT1.

Animals↗

[Clinical results of extracorporeal shock wave lithotripsy for upper urinary tract stone using Siemens Lithostar2].

Between May 1994 and March 1996, a total of 427 cases of upper urinary tract stones were treated by extracorporeal shock wave lithotripsy (ESWL) using a Siemens Lithostar2. Of 427 patients, 167 had renal stones and 260 had ureteral calculi. A double J stent was inserted preoperatively for patients with stones > or = 20 mm in diameter. The success rate after 3 months, defined as complete disappearance of stone or partial disintegration with residual stones < or = 4 mm in diameter, was 82.4% and 88.1% for the renal and ureteral calculi, respectively. Additional treatments were required in 9 cases (transurethral ureterolithotripsy in 5, percutaneous nephrostomy in 2, nephrolithotripsy and ureterolithotomy in 1 each). There were no serious side effects requiring surgical treatment or blood transfusion, although perirenal hematoma developed in 5 patients, who were treated conservatively. It is concluded that ESWL using Simens Lithostar 2 is safe and useful for treating upper urinary tract stones.

Adult↗

[A case of bilateral upper urinary tract tumors after radical cystectomy].

We report a case of bilateral upper urinary tract tumors after total cystectomy. A 67-year-old male with multiple bladder tumors underwent total cystectomy and ileal conduit urinary diversion. Pathological diagnosis was transitional cell carcinoma, grade 3 (G3), pT1b. Followup urinary cytology continued to be negative. Percutaneous antegrade pyelography revealed multiple bilateral upper urinary tract tumors 21 months post-operatively. Bilateral nephroureterectomy and resection of ileal conduit were performed. Pathological examination revealed transitional cell carcinoma, G3 in bilateral pelvis and ureter. Routine careful examination is necessary after total cystectomy.

Aged↗

A sudden death from the rupture of a small intestine firstly suspected of acute pancreatitis.

A 51-year-old drunken male was carried to a hospital with acute abdominal pain and was suspected of acute pancreatitis. The patient was treated with fasting, electrolyte transfusion, and anodyne, but took a sudden turn for the worse and died in 16 hours. In the judicial autopsy, rupture of a small intestine was detected. As the police investigated, he had been kicked in the abdomen by an assailant before coming to the hospital. The cause of death was diagnosed to be acute peritonitis due to the rupture of a small intestine. Several problems were pointed out on medical examinations and treatments of this case.

Acute Disease↗

[A case of cerebral aneurysm using a goose neck snare to stabilize the guiding catheter during embolization].

Severe arteriosclerotic changes often prevent navigating a guiding catheter into an appropriate position during aneurysm embolization. A basilar superior cerebellar artery aneurysm was found in a patient who had had subarachnoid hemorrhage 6 months previously. We selected embolization for this aneurysm using Guglielmi detachable coils (GDC) because of its highly located position from the dorsum sellae. We could not introduce a guiding catheter into the distal portion of the vertebral artery because of severe arteriosclerotic changes and it easily prolapsed into the aorta when a microcatheter was navigated through the guiding catheter positioned in the proximal vertebral artery. We were able to successfully perform embolization of the aneurysm by fixing a guiding catheter at the origin of the left vertebral artery with a goose neck snare wire introduced from the left brachial artery. The authors emphasize that a snare wire is useful not only for retrieval of foreign bodies but also for fixing a guiding catheter during aneurysm embolization, especially in which prolapse of the guiding catheter may cause a serious complication.

Catheterization↗

Identification of the histidine residues involved in substrate recognition by a rat H+/peptide cotransporter, PEPT1.

The LLC-PK1 cells stably transfected with a rat PEPT1 cDNA transported ceftibuten (anion) and cephradine (zwitterion), both oral beta-lactam antibiotics, in a H+-gradient-dependent manner. Diethylpyrocarbonate, a histidine residue modifier, abolished ceftibuten uptake. This inhibition was prevented in the presence of glycylsarcosine or cephradine. When expressed in Xenopus oocytes, replacement of either histidine 57 or histidine 121 of the rat PEPT1 with glutamine by site-directed mutagenesis eliminated ceftibuten and [14C]glycylsarcosine transport activities. Immunostaining of oocyte sections indicated that insertion of the mutant transporters in the plasma membranes was not impaired. These findings suggest that both histidine 57 and histidine 121, which are conserved in the rat, rabbit and human PEPT1, are involved in substrate recognition of this molecule.

Animals↗

Antitumor activity of a novel podophyllotoxin derivative (TOP-53) against lung cancer and lung metastatic cancer.

We synthesized a potent new antitumor podophyllotoxin derivative (4beta-aminoalkyl-4'-O-demethyl-4-desoxypodophyllotoxin; TOP-53) in our search for a drug that has strong activity against lung cancer and lung metastatic cancer. TOP-53 exhibited twice the inhibitory activity of etoposide (VP-16) against topoisomerase II and induced DNA strand breaks but showed no inhibitory activity against tubulin polymerization. The in vitro cytotoxic activity of TOP-53 assessed as IC50 was 0.016-0.37 microg/ml and 0.26-8.9 microg/ml against marine tumor and human non-small cell lung cancer (NSCLC) cell lines, respectively. TOP-53 exerted significant efficacy equivalent to that of VP-16 on s.c.-implanted murine solid tumors (Colon 26, B16-BL6, and Lewis lung carcinoma) at doses 3-5 times lower than that of VP-16. In human tumor xenografts using NSCLC, TOP-53 was active for four of five tumors, whereas VP-16 was active for two of five tumors. Potent inhibitory activity of TOP-53 was also found against a lung tumor (Lewis lung carcinoma) and four lung metastatic tumors (NL-22 and NL-17 colon cancer, UV2237M fibrosarcoma, and K1735M2 melanoma). TOP-53 appeared to be more active against four of them than VP-16. Thus, TOP-53 is not only active against s.c.-implanted lung cancers but also strongly active against lung localized tumor and metastatic tumors in the lungs. The high selectivity of TOP-53 was attributed to its high distribution into the lung and its persistence. TOP-53 is expected to be highly effective against lung cancer including NSCLC and various lung metastatic tumors in the clinical field.

Animals↗

Molecular cloning and tissue distribution of rat peptide transporter PEPT2.

A cDNA encoding rat H(+)- coupled peptide transporter PEPT2 was isolated. The cDNA encoded a protein of 729 amino acids with 48% amino acid identity to the rat PEPT1. The mRNA expression of rat PEPT2 was predominant in the kidney. When expressed in Xenopus oocytes, rat PEPT2 stimulated the uptake of bestatin, a dipeptide-like drug.

Amino Acid Sequence↗

Substrate specificity of rainbow trout testis CMP-3-deoxy-D-glycero-D-galacto-nonulosonic acid (CMP-Kdn) synthetase: kinetic studies of the reaction of natural and synthetic analogues of nonulosonic acid catalyzed by CMP-Kdn synthetase.

In this report we present kinetic data of the activation reaction of several synthetic 3-deoxy-D-glycero-D-galacto-nonulosonic acid (Kdn) and N-acetylneuraminic acid (Neu5Ac) analogues catalyzed by the rainbow trout testis CMP-Kdn synthetase. This enzyme showed broad substrate specificity in terms of substitutions at C4 or C5 position of Kdn and Neu5Ac. In contrast, calf brain CMP-N-acylneuraminic acid synthetase had narrow substrate specificity, being active only on various N-acyl analogues of Neu5Ac and only slightly active on Kdn derivatives. Usefulness of the trout testis enzyme for synthesis of various CMP-sialate analogues, which could be donor substrates for sialyltransferases, was demonstrated.

Animals↗

Induction, localization, and purification of a novel sialidase, deaminoneuraminidase (KDNase), from Sphingobacterium multivorum.

Recently, we reported the discovery of a new type of sialidase, KDNase, which specifically hydrolyzes the ketosidic linkages of 2-keto-3-deoxy-D-glycero-D-galacto-nononic acid (KDN), but not N-acylneuraminyl linkages. We now report that this enzyme, designated KDNase SM, is an inducible enzyme that is localized in the periplasm of Sphingobacterium multivorum. Growth of S. multivorum in the presence of KDN-containing oligosaccharide alditols, KDNalpha2-->3Galbeta1-->3GalNAc alpha1-->3[KDNalpha2--> (8KDN alpha2-->)n-->6]GalNAcol, as a sole carbon source induced KDNase SM activity 15 40-fold, compared with growth in the absence of inducer. KDN, Neu5Ac, or Neu5Ac oligomers were ineffective as inducers. The enzyme was released from the periplasm of induced cells by cold osmotic shock and purified 700-fold to homogeneity. The specific activity of the pure enzyme was 82,100 units/mg of protein. KDNase SM activity resided in a single polypeptide chain with an estimated molecular weight of approximately 47,500. Enzyme activity was maximal at near neutral pH. The availability of pure KDNase will now make it possible to study the structure and functional role of KDN-glycoconjugates and to determine the molecular mechanism whereby the enzyme can discriminate between KDN and N-acylneuraminic acid.

Chromatography, Ion Exchange↗