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T Sugihara

Publications and source records attributed to T Sugihara.

At least 37 records · Page 2Linked to original sources
PubMed2001

AS-924, a novel, orally active, bifunctional prodrug of ceftizoxime: physicochemical properties, oral absorption in animals, and antibacterial activity.

AS-924 is an oral prodrug of the antibiotic ceftizoxime (CTIZ), a parenteral use cephalosporin. This novel prodrug, produced by esterifying CTIZ with a lipophilic pivaloyloxymethyl (POM) group and introducing a water soluble L-alanyl group, is expected to increase the bioavailability and thereby, augment the antibacterial activity of CTIZ in vivo compared with existing prodrugs. To study the effect of the L-alanyl group in AS-924 on its bioavailability, the plasma concentration profiles of CTIZ in dogs were examined following the dosing of AS-924 and CTIZ-POM, in powder form, after pretreatment with the antacid ranitidine, and following the dosing of AS-924 after pretreatment with a gastrointestinal motility stimulant metoclopramide or suppressant scopolamine butylbromide. The absorption rate of AS-924 was constant under these different conditions due to its unique balance of lipophilicity and water solubility. CTIZ is as antibacterially active as pre-existing oral cephalosporins against Gram-positive clinical isolates, while being more active against all Gram-negative isolates-particularly Enterobacteriaceae and Haemophilus influenzae. A simulation model for the eradication profile of bacteria in computer programmed pharmacokinetic (PK) system was carried out to study the antibacterial action of CTIZ in human. CTIZ was proven to eradicate Streptococcus pneumoniae and H. influenzae effectively, while cefpodoxime (CPOD), the active moiety of CPOD proxetil, eradicated S. pneumoniae, but not H. influenzae. These results confirm that, AS-924 is a potent oral antibiotic and would be expected to be clinically effective and efficient.

Administration, Oral↗
PubMed2001

Effect of antacid pretreatment on the pharmacokinetics of AS-924, a novel ester-type cephem antibiotic--comparison with cefteram-pivoxil.

The effect of pretreatment with ranitidine, an antacid, on the absorption of AS-924, a novel prodrug-type cephem antibiotic derived from ceftizoxime (CTIZ), was examined in eight healthy adult male volunteers by the cross-over method, using cefteram-pivoxil (CTER-PI) as the control drug. The C(max) and area under the concentration (AUC) values and cumulative urinary excretion rate (0-24 h) of cefteram (CTER) after administration of CTER-PI decreased by 32, 38 and 37%, respectively, in the ranitidine pretreatment group whereas those of AS-924 were not affected by the antacid. The urinary levels of pivaloyl-carnitine determined to evaluate the solubility of these antibiotics in the gastrointestinal tract suggested that this was not affected by ranitidine. These results indicate that the absorption of CTER-PI was affected by pretreatment with ranitidine largely due to inactivation of this antibiotic in the gastrointestinal tract at high pH rather than to a decrease in solubility. In contrast, isomerization of AS-924 was hardly induced by the elevation of pH, thus demonstrating that AS-924 was less likely to be affected by pretreatment with antacids.

Absorption↗
PubMed2001

Effects of the quantity of water and milk ingested concomitantly with AS-924, a novel ester-type cephem antibiotic, on its pharmacokinetics.

The effect of the quantity of water ingested concomitantly with drugs, on the absorption of AS-924, a novel prodrug-type cephem antibiotic, was studied in five healthy adult volunteers by a cross-over method, using cefteram-pivoxil (CTER-PI) as the control drug. In addition, the effect of milk on the absorption of AS-924 was also investigated. The absorption of CTER-PI was significantly reduced when administered together with 30 ml of water compared with its absorption when administered together with 150 ml of water, whereas no such reduction was found in the case of AS-924. Ingestion of milk did not significantly affect the absorption of AS-924. These results confirm that absorption of AS-924 after oral administration is not likely to be affected by the quantity of water taken concomitantly with the drug, nor by milk.

Administration, Oral↗
PubMed2001

Cell cycle analysis and expression of cell cycle regulator genes in myeloma cells overexpressing cyclin D1.

Among the recently discovered myeloma-specific gene alterations associated with chromosomal translocations, cyclin D1/PRAD1/Bcl-1 overexpression caused by t(11;14)(q13;q32) is considered to be the most frequent in myeloma patients and cell lines, and may be a prognostic factor clinically. To elucidate the cellular biological role of overexpressed cyclin D1 in myeloma cells, we examined the mRNA expression levels of cell cycle regulators including three cyclin Ds, cyclin-dependent kinase inhibitors (CDK-Is) and accelerators. Cyclin D1 overexpression was clearly demonstrated in the lines with abnormal 11q13 and associated with overexpression of S and G2 accelerator genes. The cyclin D1-overexpressing lines tended to have a shortened G1 phase compared with the non-expressing lines. In addition, artificial silencing using antisense oligonucleotides for cyclin D1 suppressed the growth rate of some but not all cyclin D1-overexpressing cells. These results indicate that overexpression of cyclin D1 caused by cytogenetic abnormalities may make cells progress through the cell cycle rapidly, but it seems that other factors such as cyclin D2 and translocation-related genes affect the cell cycle progression in myeloma cells.

Cell Cycle↗
PubMed2001

Two innovations of the star-flap technique for nipple reconstruction.

Two innovations of the star-flap technique for nipple reconstruction are described. A combination of the star-flap technique and a contralateral nipple graft is indicated in patients with a large nipple and small areola on the contralateral side. It provides sufficient volume for the new nipple and improves the shape of the donor nipple. A combination of the star-flap technique and a banked costal-cartilage graft offers better nipple contour and projection than the conventional star-flap technique. Preparation of the cartilage graft is easy and does not result in additional scarring; the nipple projection can be expected to be maintained over a long period.

Adult↗
PubMed2001

[Whole-body MR imaging for evaluation of bone marrow cellularity in aplastic anemia].

The aim of this study was to investigate the usefulness of whole-body MRI(WB-MRI) in the evaluation of cellularity in bone marrow and the distribution of fatty marrow in aplastic anemia. WB-MRI was performed on five patients with aplastic anemia who ranged in age from 62 to 70 years of age, and on four controls with malignant lymphoma who ranged in age from 59 to 67 years. Coronal images were obtained using a body coil with an FOV of 48 cm x 48 cm, and with both fast short T1 inversion recovery(STIR) and spin-echo T1-weighted(T1-WI) in three regions: (1) head to thorax, (2) abdomen to pelvis, and (3) lower extremities. The findings on WB-MRI were compared with those of histological studies of bone marrow at the sternum and the posterior iliac crest. The results were as follows: (1) there was a correlation between the cellularity of histological studies of bone marrow and signal intensity on WB-MRI; (2) WB-MRI could detect the activity of bone marrow; and (3) in a comparison of signal intensity in aplastic anemia and control subjects, there were differences of signal intensity in the central marrow.

Aged↗
PubMed2000

Selective toxicity of MKT-077 to cancer cells is mediated by its binding to the hsp70 family protein mot-2 and reactivation of p53 function.

MKT-077, a cationic rhodacyanine dye analogue has been under preclinical cancer therapeutical trials because of its selective toxicity to cancer cells. Its cellular targets and mechanism of action remain poorly understood. Here we report that MKT-077 binds to an hsp70 family member, mortalin (mot-2), and abrogates its interactions with the tumor suppressor protein, p53. In cancer cells, but not in normal cells, MKT-077 induced release of wild-type p53 from cytoplasmically sequestered p53-mot-2 complexes and rescued its transcriptional activation function. Thus, MKT-077 may be particularly useful for therapy of cancers with wild-type p53.

3T3 Cells↗
PubMed2000

A staining procedure for micronucleus test using new methylene blue and acridine orange: specimens that are supravitally stained with possible long-term storage.

The micronucleus test has been widely used as an in vivo cytogenetic test. It employs two different kinds of supravital staining methods which use either new methylene blue (N) and Giemsa (G) or acridine orange (AO). We have developed a new staining procedure for the preparation of specimens supravitally stained with possible long-term storage, using both N and AO. This N/AO-staining method involves three steps; (1) combination of the target tissue or target cells with an equivalent volume of 0.5% solution of new methylene blue (N-staining step), (2) immediate smear of the mixture, followed by treatment with methanol for 10 min for fixation and removal of N and drying (referred to as fixed-decolorized specimens), and (3) staining with 0.007% solution of AO for 3 min, followed by washing with Sörensen's buffer (pH 6.8) and covering of specimens before observation (AO-staining step). To examine whether the N/AO-staining method is useful for the micronucleus test, comparisons were made between N-, N/AO-, and AO-stained specimens prepared supravitally from peripheral blood of rats with and without treatment of cyclophosphamide. The results indicate that N/AO-stained specimens can be supravitally observed after long-term storage with the same coloration and comparable frequencies of micronucleated reticulocytes with a positive response as AO-stained specimens, if the staining process is temporarily stopped before AO-staining (as fixed-decolorized specimens), or if the AO-staining step is repeated. The results also showed that separated reticulocyte types are supravitally stained in a similar fashion to N-stained specimens but not to AO-stained specimens, indicative of the preservation of the supravital feature of N-staining. Taken together these results suggest that the N/AO-staining procedure could offer an additional useful staining tool for the micronucleus test.

Acridine Orange↗
PubMed2000

Gros1, a potential growth suppressor on chromosome 1: its identity to basement membrane-associated proteoglycan, leprecan.

By immunoscreening with an antibody raised against a plasma membrane protein, we have cloned a growth suppressor gene, Gros1 and assigned it to short arm of human chromosome 1. Two alternatively spliced forms of the gene encoding 84- and 41-kDa (carboxy-terminus truncated) proteins were cloned. The two transcripts, 4.4 and 2.7 kb, were expressed weakly in most of the human tissues, with a high expression of the smaller transcript in placenta, ovary and testis. Normal human fibroblasts in culture showed two transcripts, with a higher level of expression of the 4.4 kb transcript. Transformed cells on the other hand showed predominant expression of the 2.7 kb transcript. Two Gros1 transcripts were also detected in most of the mouse tissues. Stable transfection of the mouse cDNA encoding the 85-kDa protein into NIH3T3 cells resulted in their slow growth and reduced colony-forming efficiency. Stable clones expressing antisense RNA on the other hand exhibited higher colony forming efficiency. While our data implied that Gros1 is a novel growth suppressor gene on human chromosome 1, an independent study has recently characterized its rat-homolog as a leucine proline-enriched novel basement membrane-associated proteoglycan leprecan. We describe here cloning, expression and biological activity analysis implying that this novel proteoglycan is a potential growth suppressor on chromosome 1p31, frequently altered in many malignancies.

3T3 Cells↗
PubMed2000

Structurally and functionally distinct mouse hsp70 family members Mot-1 and Mot-2 proteins are encoded by two alleles.

The mouse mortalin proteins Mot-1 and Mot-2 differ by two amino acids in their carboxy-terminus. These proteins are differentially localized in the cell cytoplasm and have contrasting biological activities. The genetic relationship between Mot-1 and Mot-2 was deciphered by mouse family analyses. Mot-1 and Mot-2 segregated in F1 and F2 progeny, providing direct evidence that the two proteins are encoded by two alleles.

Alleles↗
PubMed2000

The C-ring problem of sterol biosynthesis: TiCl(4)-induced rearrangement into the anti-Markovnikov cation corresponding to the C-ring.

[reaction: see text] Cation 9, generated by the reaction of diol 8 and BF(3).Et(2)O, SnCl(4), Sc(OTf)(3), FeCl(3), TiF(4), or CF(3)SO(3)H, leads to a hydride shift, providing cation 11, which corresponds to the initiation of backbone rearrangement. On the other hand, TiCl(4) selectively induces rearrangement to secondary cation 13 by ring expansion, which corresponds to the C-ring formation of sterol biosynthesis. AlCl(3) and ZrCl(4) induce further rearrangement into six-membered ring tert-cation 16.

Cations↗
PubMed2000

Inner ear abnormalities in Kabuki make-up syndrome: report of three cases.

Three patients, a female and two males, 28, 15, and 14 years of age, with Kabuki make-up syndrome (KMS) were studied for middle and inner ear abnormalities by using CT scanning of the petrous bones. All three patients had bilateral dysplasia of the inner ear, i.e., hypodysplasia of the cochlea, vestibule, and semicircular canals (so-called Mondini dysplasia), whereas their middle ears had no abnormalities. Audiometry demonstrated a sharp decrease in hearing of the high tone range, bilateral in one and unilateral in another, while the third patient was noncooperative. In view of these findings, it would be advisable to study each individual with KMS and hearing impairment for possible inner ear abnormalities.

Abnormalities, Multiple↗
PubMed2000

Nasal NK/T cell lymphoma presenting as transverse myelopathy.

A case of nasal NK/T cell lymphoma with central nervous system (CNS) involvement is reported. A 56-year-old man presented with eyelid edema and transverse myelopathy. Cerebrospinal fluid examination revealed atypical lymphoid cells with azurophilic granules, which were positive for CD2, CD8, and CD56, and negative for CD3 and CD5 by flow cytometry. Because a tumor mass was found involving the ethmoid and maxillary sinuses, CNS involvement was considered to have resulted from local invasion by the nasal lymphoma. In spite of intensive chemotherapy including intrathecal infusion, the patient died 6 months after the initial diagnosis. Autopsy revealed that lymphoma cells were positive for cytotoxic molecules, granzyme B and TIA-1, and EB virus-encoded RNA-1 (EBER-1), and they showed no rearrangement of TCR-beta, -gamma, or -delta genes, suggesting an NK-cell origin of the lymphoma cells. They showed an angiocentric and angiodestructive pattern in the subarachnoid space, focally extending to the cerebral cortex and cranial and spinal nerve roots. Marked demyelination was found in the lateral and posterior funiculi of the spinal cord. Thus, the pathogenesis of this spinal demyelination might be attributed to ischemia secondary to angiocentric and angiodestructive infiltration by lymphoma cells.

Diagnosis, Differential↗
PubMed2000

Keloid-derived fibroblasts are refractory to Fas-mediated apoptosis and neutralization of autocrine transforming growth factor-beta1 can abrogate this resistance.

The pathogenesis of keloid remains poorly understood. As no effective therapy for keloid is as yet available, an insight into its pathogenesis may lead to novel approaches. Apoptosis has been found to mediate the decrease in cellularity during the transition between granulation tissue and scar. Here, we report that in contrast to hypertrophic scar-derived and normal skin-derived fibroblasts, keloid-derived fibroblasts are significantly resistant to both Fas-mediated and staurosporine-induced apoptosis. The caspases-3, -8, and -9 were not activated indicating that the block in the apoptotic pathway in keloid is upstream of the caspases. There were no significant differences in the level of expression of Fas, Bcl-2, and Bax between the three groups but addition of transforming growth factor (TGF)-beta1 significantly inhibited Fas-mediated apoptosis in hypertrophic scar-derived and normal skin-derived fibroblasts and neutralization of autocrine TGF-beta1 with anti-TGF-beta1 antibody abrogated the resistance of keloid-derived fibroblasts. Anti-apoptotic activity was not observed with TGF-beta2. This is the first study linking refractory Fas-mediated apoptosis to cellular phenotype in keloids and indicating a pivotal role for the anti-apoptotic effect of TGF-beta1 in this resistance. Hence, it becomes important to treat keloids as a separate entity different from hypertrophic scars and enhancement of Fas-sensitivity could be a promising therapeutic target.

Antibodies↗
PubMed2000

Experience with 24 cases of reconstructive anterior skull base surgery: classification and evaluation of postoperative facial appearance.

This article details our experience with 24 cases of anterior skull base reconstruction after tumor resection. They were classified into four types according to the resected region. In 11 cases of type I resection, the orbital part of frontal bone and/or cribriform plate of ethmoid bone were resected. In two cases of type II resection, the orbital contents and partial orbital bone were resected with the addition of type I. In five cases of type III resection, the maxillary bone was resected with the addition of type II. In six cases of type IV resection, the zygomatic bone and/or facial skin were resected with the addition of type III. The tumor originating from intracranial region was 25% of this series and all of them belonged to type I. The tumor originating from extracranial region tumor was 75% and its resected region was more extensive. In type I and II resections, the cranial flap, radial forearm free flap, or a combination of the two was used for reconstruction. The rectus abdominis myocutaneous/muscle free flap was used for reconstruction of massive defects in type III and IV defects. Total incidence of postoperative complications was 16.7%. Donor site deformity of the cranial flap at the frontal and temporal region in types I and II resections and facial contour deformity in zygomatic region and defect of upper and/or lower palpebra in type IV resection were major problems with postoperative facial appearance. Although use of the rectus abdominis myocutaneous free flap combined with costal cartilages improved the midfacial contour, palpebral reconstruction remained an unsolved problem in reconstructive skull base surgery. The reconstructive goals in skull base surgery are not only to obtain safe and reliable skull base reconstruction but also to restore the facial appearance postoperatively.

Journal Article↗
PubMed2000

Technique for selective microangiography of skin flaps with high contrast and fine detail.

The technical factors of microangiography were studied, and the authors found that the main limiting factors in resolution were the injection pressure of the contrast medium and the thickness of the materials. A gentle manual hand pressure injection, with the aid of visual monitoring under the operating microscope, were keys to obtaining beautiful microangiograms.

Angiography↗