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Biomedical subjects

T Katayama

Publications and source records attributed to T Katayama.

At least 145 records · Page 8Linked to original sources
PubMed1996

Molecular design of inhibitors of in vitro oriC DNA replication based on the potential to block the ATP binding of DnaA protein.

DnaA protein, the initiation factor for chromosomal DNA replication in Escherichia coli, is activated by binding to ATP. We earlier reported that 3-acetoxy-2,2'-bi-1H-indol inhibited the ATP binding to DnaA protein (Sasaki, S., Mizushima, T., Hashimoto, T., Maeda, M., and Sekimizu, K. (1994) Bioorg. Med. Chem. Lett. 4, 1771-1774). In the present study, derivatives of 3-acetoxy-2,2'-bi-1H-indol with different lengths of aliphatic chains at the 3-O position were synthesized, and their potential to inhibit the ATP binding to DnaA protein was examined. Elongation of the aliphatic chain resulted in inhibition of the ATP binding to DnaA protein at lower concentrations. Among the derivatives, 3-[N-(11-carboxyundecyl)]carbamoylmethoxy-2,2'-bi-1H-indol (structure 7 (3-CUCM-BI)) exhibited the most potent inhibition with an IC50 value of 7 microM. The mode of the inhibition was competitive. We further demonstrated that structure 7 (3-CUCM-BI) inhibited DNA replication of the oriC plasmid in a system reconstituted from purified proteins. This inhibition was specific for the initiation of DNA replication rather than for the elongation. The inhibition was overcome by preincubation of DnaA protein with ATP. Furthermore, structure 7 (3-CUCM-BI) showed little inhibition on DNA synthesis in the ABC primosome system. We propose that structure 7 (3-CUCM-BI) functions in the in vitro oriC DNA replication by inhibiting the ATP binding to DnaA protein.

Adenosine Triphosphate↗
PubMed1996

Effect on DNA topology by DnaA protein, the initiation factor of chromosomal DNA replication in Escherichia coli.

We examined effects on supercoiled DNA topology of DnaA protein, the initiator protein of chromosomal DNA replication in Escherichia coli. The activity was identified in an analysis of plasmid DNA incubated with DnaA protein and DNA topoisomerase I. In Superose 12 gel filtration chromatography, the activity coeluted with DnaA protein. Incubation of DnaA protein with DNA at temperatures over 24 degrees C was required for this activity, which was observed with either oriC plasmid or the replicative form I of phi X174 with no DnaA box. As binding of ATP or ADP to DnaA protein prevented the activity of DnaA protein on DNA topology, binding of the adenine nucleotide may regulate the activity.

Adenosine Diphosphate↗
PubMed1996

Fibronectin harbors anticell adhesive activity.

Effect of fibronectin (FN) fragment derived from the carboxyl-terminal heparin-binding (Hep 2) domain on cell adhesion was studied. A 30-kDa Hep 2 fragment showed no significant effect on adhesion of Mardin Darbyn caine kidney (MDCK) cells to FN substrate, whereas after exposure to urea, the Hep 2 fragment suppressed the MDCK cell adhesion to FN in an incompetitive fashion. This anti-cell adhesive Hep 2 fragment preferentially inhibited the RGD (Arg-Gly-Asp)-dependent cell adhesion to FN. No significant binding of the Hep 2 fragment with FN was detected. Additionally, data of flow cytometry showed the presence of specific binding site for the Hep 2 fragment on MDCK cell surface. These results indicate that the Hep 2 domain of FN has a cryptic molecular region having the anti-cell adhesive activity that is probably transduced by a putative cell surface receptor.

Amino Acid Sequence↗
PubMed1996

Influence of cluster formation of acidic phospholipids on decrease in the affinity for ATP of DnaA protein.

DnaA protein is the initiator of chromosomal DNA replication in Escherichia coli. We examined the influence of artificial mixed membrane composed of synthetic acidic (phosphate) lipid and basic (ammonium) lipid on the affinity of DnaA protein for ATP. Two sets of acidic and basic lipids with distinguishable numbers of hydrophobic alkyl chains were devised. Synthetic membranes made of the sole acidic lipid but not the basic bilayers inhibited the ATP binding to DnaA protein and stimulated the release of ATP from the ATP-DnaA complex. The basic bilayer-forming compounds served as the matrix for the guest acidic lipids. Acidic lipids dispersed in the basic matrix membrane had little effect on ATP binding and on ATP release. Conversely, acidic lipids forming cluster structures in the mixed artificial membranes inhibited the ATP binding and stimulated the release of ATP. These observations suggest that in mixed lipid bilayers, a cluster structure of acidic lipids seems to be an important parameter to decrease the affinity of DnaA protein for ATP.

Adenosine Triphosphate↗
PubMed1996

Transcellular biosynthesis of cysteinyl leukotrienes by Kupffer cell-hepatocyte cooperation in rat liver.

We previously proposed that an enzymatic cooperation between Kupffer cells and hepatocytes may play an important role in cysteinyl leukotriene (LT) production in rat liver. An in vitro transcellular synthesis cysteinyl LTs by a Kupffer cell-hepatocyte coculture system was characterized here. Kupffer cells alone, with A23187 stimulation, did not generate cysteinyl LTs until supplemented either with isolated hepatocytes or with LTC4 synthase and glutathione, indicating that Kupffer cells can synthesize LTA4 but not convert it into LTC4. In contrast, hepatocytes converted the LTA4 into cysteinyl LTs and further degraded the cysteinyl LTs. Cysteinyl LT production by the Kupffer cell-hapatocyte coculture system was optimized by addition of 1-3% serum albumin to the culture and by bringing the cell-cell distance closer to less than 3 mu. Tumour necrosis factor also stimulated cysteinyl LT production by the coculture system. From these results, it is expected that the Kupffer cell-hepatocyte transcellular system for cysteinyl LT production actually functions in vivo.

Animals↗
PubMed1996

Etoposide, epirubicin and carboplatin in hormone-refractory prostate cancer.

Twelve patients with hormone-refractory prostate cancer were treated with combination chemotherapy of etoposide, epirubicin and carboplatin (EEC). At relapse, all patients had metastases to the bone and/or soft tissues. The median number of courses was 3 (range 1-10). Epirubicin was not administered in 6 patients because of heart disease. Three patients (25%) had a partial response and 8 (67%) showed no change. The overall response rate was 92%. Pain relief was observed in 4 patients (44%). Four patients were still alive after a mean observation period of 18 months (range 4-36 months), while 8 died with a mean survival period of 11 months (range 7-15 months). Nausea, appetite loss, and alopecia were observed in some patients. All except one patient experienced bone marrow suppression, 5 of whom were treated with granulocyte-colony stimulating factor. EEC chemotherapy in hormone-refractory prostate cancer is considered to be more effective than other kinds of chemotherapy, whereas it frequently induces bone marrow suppression.

Aged↗
PubMed1996

Laparoscopic varicocele ligation.

Varicocele, an abnormal dilatation of the pampiniform plexus, frequently contributes to male factor infertility. We performed laparoscopic varicocelectomy in 20 patients with varicoceles and abnormal seminal findings. The spermatic artery was identified and preserved in 13 patients and was clipped along with the veins in 7 patients including 1 patient with bilateral varicocele. The time required for the artery-ligating surgery ranged from 90 to 120 minutes with an average of 113.2 minutes, while the time needed for the artery-preserving technique ranged from 90 to 250 minutes with an average of 158.0 minutes. Some analgesics were administered to 11 patients, while the other 9 patients needed no analgesics. All patients were able to walk within 24 hours of the operation. The mean hospitalization period after the operation was 5.9 days. Sperm concentrations significantly improved postoperatively (p < 0.05). No difference in postoperative improvement of seminal findings was observed between artery-ligating and artery-preserving groups. A slight scrotal emphysema developed during the operation in 1 patient. Abdominal pain was experienced in 1 patient, but subsided within a few days. No serious complications were observed. The laparoscopic technique may replace routine open high ligation as the surgical treatment of choice, especially in patients with bilateral varicocele.

Adult↗
PubMed1996

Gonadotropin therapy in males with hypogonadotropic hypogonadism: factors affecting induction of spermatogenesis after gonadotropin replacement.

Sixteen patients with hypogonadotropic hypogonadism received gonadotropin replacement therapy. Two patients treated with HCG alone showed induction of spermatogenesis 2 and 12 months after the start of treatment. Three subjects receiving combination therapy showed sperm appearance 6-28 months after treatment. The patients showing sperm appearance, whose testicular volume was > or = 4 ml, showed a higher sperm count and impregnated their partners, although no relationship was found between pretreatment testicular volume and sperm appearance. The response to HCG test correlated with sperm appearance after gonadotropin therapy. Sperm appearance was not observed in any subject except for one who showed no response to luteinizing hormone-releasing hormone (LH-RH) test and none of the patients without response of FSH to LH-RH demonstrated any induction of spermatogenesis. In conclusion, the responses to LH-RH test and possibly to HCG test could predict the induction of spermatogenesis after gonadotropin replacement therapy, and a large testicular volume is associated with post-treatment fertility.

Adolescent↗
PubMed1996

Measurement of residual urine volume using a portable ultrasound instrument.

A portable ultrasound unit (BladderScan BVI 2000) has been developed which offers a non-invasive procedure to determine urine volume. This study was undertaken to evaluate the accuracy of measurements by this method. A high correlation was demonstrated between the catheterized volume and ultrasound estimation (r = 0.98, p < 0.0001). In patients with residual urine of > 50 ml, the unit could correctly identify 93%. This instrument is useful in estimating the residual urine volume, and its application is recommended as an alternative to catheterization for the determination of residual urine.

Adult↗
PubMed1996

Effects of daily injections of melatonin on locomotor activity rhythms in rats maintained under constant bright or dim light.

It has been demonstrated that daily melatonin injections entrain free-running locomotor activity rhythms in rats kept in constant darkness, and synchronize disrupted circadian patterns of wheel-running activity under constant light. Contrary to these previous observations, our result did not show that daily injections of melatonin synchronize disrupted locomotor activity in rats maintained under constant bright light. On the other hand, daily treatment with melatonin entrained the intact free-running rhythm in rats kept in constant dim light. This entrainment took place only when the time of injection corresponded to the activity onset time, and similar results were obtained in blinded rats. Pinealectomy had no influences on either the free-running rhythm or melatonin-induced entrainment. To examine whether a behavioral feedback mechanism is involved in melatonin-induced entrainment, rats were immobilized for 3 h after each daily melatonin injections. This did not interfere with melatonin-induced entrainment. These results suggest that the mechanism underlying melatonin-induced entrainment of activity rhythms may be different from those in photic and behavioral entrainment.

Animals↗
PubMed1996

Is thrombomodulin useful as a tumor marker of a lung cancer?

To evaluate whether thrombomodulin (TM) can be considered a tumor marker of lung cancer, we examined serum TM levels in 179 lung cancer patients by an enzyme immunoassay. Further, in 91 resected cases, we also investigated the TM presence in lung cancer tissue by an immunohistochemical method. Our findings revealed that 58 (32%) of 179 lung cancer patients had higher serum TM levels than our cutoff levels. No difference was seen in the serum TM-positive ratio between histologic types, but patients with Stage IV disseminated cancer showed a higher serum TM-positive ratio than those with Stage I-IIIB localized cancer, especially cases of adenocarcinoma. Immunostaining results showed a TM presence in the cancer cells of 32 (35%) of 91 lung cancer cases. The TM presence in cancer cells was higher in cases with squamous cell carcinoma than with adenocarcinoma; no differences were seen among the disease stages. No correlation was found between the serum TM and the presence of TM in cancer cells. Further, serum TM status appears to have little clinical significance as a method to detect early lung cancer or for predicting the recurrence after the surgical excision of a lung cancer. Thus, we have concluded that, although serum TM levels are elevated in some lung cancer patients, it is doubtful that the TM status is useful as a tumor marker of lung cancer.

Adenocarcinoma↗
PubMed1996

[Spotted fever group rickettsiosis and vectors in Kanagawa prefecture].

Primer pairs for PCR were designed from the gene encoding the 17,000-molecular-weight genus-common antigen of Rickettsia japonica, Rickettsia rickettsii, Rickettsia conorii, Rickettsia typhi and Rickettsia prowazekii. Primers R1, R2 were designed for amplifying the genomic DNA from spotted fever group (SFG) rickettsiae and epidemic typhus rickettsiae. Primers Rj5, Rj10 were designed for amplifying the genomic DNA from only R. japonica. Using the primers R1, R2, about a 540-bp fragment was observed by amplifying the genomic DNA from R. japonica, R. rickettsii, R. conorii, Thai tick typhus TT-118, Rickettsia sibirica, Rickettsia montana, Rickettsia askari, R. typhi, R. prowazekii and Katayama strain isolated from the patient infected with SFG rickettsiae. Using the primers Rj5, Rj10, the 357-bp fragment was observed by amplifying the genomic DNA from R. japonica and Katayama strain. Therefore, the Katayama strain was identified to belong to R. japonica. With primers R1, R2 and Rj5, Rj10, 537 bp and 357 bp bands were amplified from blood of the patients infected with SFG rickettsiae in Kanagawa prefecture. These findings indicate that the causative agent of SFG rickettsiosis in these two patients was R. japonica. The ticks, Ixodes ovatus and Haemaphysalis flava, were collected by out field research in Kanagawa prefecture. With primers R1, R2 and Rj5, Rj10, 537 bp and 357 bp were amplified from these ticks. This indicates that I. ovatus and H. flava were the vector of R. japonica in Kanagawa prefecture. Also, with the primers R1, R2, about a 540 bp fragment was amplified but with primers Rj5, Rj10, no fragments were amplified from I. ovatus and H. flava. Therefore, these ticks may have SFG rickettsiae other than R. japonica and epidemic typhus rickettsiae.

Animals↗
PubMed1996

The nucleoid protein H-NS facilitates chromosome DNA replication in Escherichia coli dnaA mutants.

Growth inhibition of the dnaA(Cs) mutant, which overinitiates chromosome replication, was shown to be dependent upon the nucleoid protein H-NS. [3H]thymine incorporation experiments indicated that the absence of H-NS inhibited overreplication by the dnaA(Cs) mutant. In addition, the temperature-sensitive phenotype of a dnaA46 mutant was enhanced by disruption of H-NS. These observations suggest that H-NS directly or indirectly facilitates the initiation of chromosome replication.

Bacterial Outer Membrane Proteins↗
PubMed1996

Effect of carboplatin on rat spermatogenesis.

To examine the effect of carboplatin on testicular function, carboplatin was administered to mature male Sprague-Dawley rats. Four weeks after carboplatin treatment, the serum level of follicle-stimulating hormone (FSH) significantly increased in animals treated with 30 mg kg-1 carboplatin (p < 0.02). After 8 weeks of administration, the sperm count and motility in the cauda epididymis decreased in the rats treated with 30 mg kg-1 carboplatin (p < 0.005 and p < 0.05, respectively). The percentage of a-type tubules and the diameter of seminiferous tubules were also significantly reduced in the group treated with 30 mg kg-1 carboplatin (p < 0.02 and p < 0.01, respectively). The serum levels of luteinizing hormone and testosterone were not changed, although the serum level of FSH increased in the animals treated with 20 and 30 mg kg-1 carboplatin (each, p < 0.005). All parameters returned to normal values 12 weeks after the treatment. In conclusion, carboplatin impairs spermatogenesis by possibly damaging the spermatogonia and Sertoli cells but does not affect the Leydig cell function.

Animals↗
PubMed1996

Effect of dietary L-glutamine on the hepatotoxic action of D-galactosamine in rats.

The protective effect of dietary L-glutamine against the hepatotoxic action of D-galactosamine (GaIN) was investigated by model experiments with rats. Rats fed with 20% casein diets containing 10% free amino acids were injected with GaIN, and the serum aspartate aminotransferase, alanine aminotransferase and lactate dehydrogenase activities and the hepatic glycogen content were assayed 20 hours after the injection. These enzyme activities in the group fed with 10% L-glutamine diet for 8 days were lower than those in the groups fed with the control, 10% L-glutamic acid and 10% L-alanine diets for 8 days. The more prolonged the feeding period with the 10% L-glutamine diet was, the more the serum activity levels of such enzymes were decreased. Although neomycin also lowered these enzyme activities, its simultaneous ingestion with neomycin did not show any additive or synergistic effect. The hepatic glycogen content in the 10% glutamine group still remained high after the GaIN treatment. It is therefore assumed that the effectiveness of glutamine intake would have been mediated by glycogen metabolism rather than by uridine metabolism.

Alanine↗
PubMed1996

Phylogenetic relationships among turbellarian orders inferred from 18S rDNA sequences.

The turbellarian flatworm is a key group to understand the origin and the early evolution of triploblastic, bilaterally symmetrical animals, but phylogenetic relationships among turbellarian orders have been a subject of debates for decades, especially on the position of the acoel turbellarians. Some workers have considered the acoel representing the most primitive turbellarian order but others have regarded them as regressive. We determined almost the entire lengths of the nucleotide sequences of 18S ribosomal RNA gene (rDNA) in 17 species from 9 turbellarian orders (the Acoela, Catenulida, Macrostomida, Lecithoepitheliata, Rhabdocoela, Prolecithophora, Proseriata, Tricladida, and Polycladida). After adding the sequences of a cestode, two trematodes and some diploblastic animals obtained from databases, we reconstructed phylogenetic trees using the neighbor-joining, maximum-likelihood and maximum-parsimony methods. All trees significantly indicated that the Acoela is the earliest divergent group among the turbellarian orders. The trees also suggested that the Tricladida evolved in the separate lineage from that of a cluster of the Catenulida, Macrostomida, Lecithoepitheliata, Rhabdocoela, Polycladida, Trematoda and Cestoda after the divergence of the Acoela.

Animals↗
PubMed1996

[The effects of cyclosporin azathioprine and mizoribine on male reproduction in rats].

BACKGROUND: The effects of cyclosporin (Cs), azathioprine (AZP) and mizoribine (MZR) on male reproduction in rats were examined. METHODS: Each drug was orally administered every day for 14 days at the following doses; Cs, 10, 20, 40, or 80 mg/kg body weight; AZP, 5, 10, or 20 mg; and MZR, 2.5, 5, 10, or 20 mg. RESULTS: In the sperm count in the cauda epididymis, two weeks after the discontinuation of administration, a significant decrease was observed only in the 80 mg/kg dose group among the Cs-treated groups and in the 5 mg/kg and 20 mg/kg dose groups among the AZP-treated groups. At the end of the administration, a significant dose-dependent decrease was observed in the MZR-treated groups. The degree of the decrease was smaller after Cs administration compared with the other 2 drugs. Sperm motility was significantly decreased in each Cs-treated group immediately after the oral administration of Cs and improved gradually, but was not changed in AZP- and MZR-treated groups. Significant dose-dependent damage of the seminiferous tubules was noted 6 weeks after administration of Cs, AZP and MZR. The serum levels of luteinizing hormone and follicle-stimulating hormone remained the same throughout the experiment. The serum level of testosterone was significantly low immediately after the oral administration of AZP, but was not changed by that of Cs and MZR. CONCLUSION: Cs, AZP and MZR injured the spermatogenesis in rat. However, changes in the sperm count in the cauda epididymis suggested that the degree of impairment by Cs is relatively small, but only Cs injured epididymal function as well.

Animals↗