PubMed Health⌕ Search

Biomedical subjects

R Hara

Publications and source records attributed to R Hara.

At least 37 records · Page 2Linked to original sources
PubMed1997

[Effect of daily administration of oral etoposide for non-small cell lung cancer treated with concurrent radiation therapy].

The purpose of this study was to explore the effect of daily administration of oral etoposide (25 mg) for patients with non-small cell lung cancer treated with concurrent radiation therapy. Planned endpoints were response, survival and toxicity. Forty-one patients with non-small cell lung cancer were divided into 25 patients given daily oral etoposide (25 mg) with concurrent radiation therapy (ERT group) and 16 patients given radiation therapy alone (RT group). Etoposide was administrated in the morning throughout radiation therapy. The median total irradiated dose was 63.1 Gy in the ERT group and 64.0 Gy in the RT group. Twenty-four patients completed therapy in the ERT group and 16 in the RT group. Three (15%) ERT patients achieved complete response (CR) and 9 (45%) achieved partial response (PR). In the RT group, no patients achieved CR and 9 (69%) achieved PR. One-year survival was 22.6% with ERT and 23.0% with RT. The prognosis of stage III patients in the ERT group was worse than that in the RT group because radiation pneumonitis and radiation esophagitis were more severe with ERT. In conclusion, the ERT group had better local response but worse in survival than the RT group. Complications of ERT were severe enough to cause death in some patients. ERT had no clear advantage over RT.

Administration, Oral↗
PubMed1996

Recovery from ultraviolet tight-induced depression of ribosomal RNA synthesis in normal human, xeroderma pigmentosum and Cockayne syndrome cells.

The rate of ribosomal RNA (rRNA) synthesis was analyzed at different times after ultraviolet light (UV) irradiation in normal human, xeroderma pigmentosum (XP) and Cockayne syndrome (CS) cells. In normal cells, the rate of rRNA synthesis, as measured by the incorporation of 3H-uridine into 18S and 28S rRNAs, decreased immediately after UV irradiation to about half of that of unirradiated cells, and then recovered significantly at 24 h after UV. However, the rate of synthesis continued to decrease during post-UV incubation in XP cells belonging to groups A, D, E, F and G, as well as in CS cells of groups A and B. In contrast, group C XP cells showed a slight recovery at 24 h after UV, suggesting that they have the capacity to repair UV lesions in rRNA genes.

Cells, Cultured↗
PubMed1996

[Clinical review of 105 cases of adrenal tumor, with special reference to incidental tumor].

We reviewed 105 patients with adrenal tumor diagnosed at our institute from January 1984 to December 1993. In 74 patients tumors were symptomatically diagnosed (the symptomatic group), while in the remaining 31 patients tumors were incidentally detected (the incidental group). In 5 cases of the incidental group, tumors were found at a routine health examination, whereas in the remaining 26 cases tumors were found during the examination or treatment for unrelated diseases. On both the incidental group and symptomatic group, higher right-to-left side ratio was noted in the laterality of tumors detected by ultrasound scanning. The size of tumors in the incidental group was significantly larger than that in the symptomatic group, but there was no significant difference in size between the tumors detected by ultrasound and those detected by CT scan in either the symptomatic group or in the incidental group. In the symptomatic group 71 patients (95.9%) were found to have functioning tumor, where the most common diagnosis was primary aldosteronism (44 cases), and 68 of the 71 patients received adrenalectomy. While in the incidental group 12 patients (38.7%) were found to have functioning tumor, where the most common diagnosis was pheochromocytoma (7 cases), followed by Cushing's syndrome (3 cases) including one case with so-called pre-Cushing's syndrome, and all of the 12 patients received adrenalectomy. Of 16 primary incidental adrenal tumors which did not have any hormonal functions, 5 tumors larger than 30 mm in diameter were resected and the remaining 11 tumors were followed up without operation. Since the incidence of incidental adrenal tumor may increase in the future, careful diagnosis and decision of indication for surgery are required.

Adolescent↗
PubMed1996

Structure-activity relationships of cephalosporins having a (dimethylisoxazolidinio)vinyl moiety at their 3-position.

A series of cephalosporins having a (dimethylisoxazolidinio)vinyl group at their 3-position were synthesized to investigate their structure-activity relationships. With regard to the olefin geometry, the (E)-vinyl compound exhibited higher in vitro activity than the (Z)-compound. Regarding the C-7 substituents, the replacement of 2-aminothiazole with 5-amino-1,2,4-thiadiazole increased the anti-pseudomonal activity. Determination of the absolute configuration of the C-3 substituent is also presented. Among the compounds synthesized, we selected 7 beta-[(Z)-2-(5-amino-1,2,4-thiadiazol-3-yl)-2-(fluoromethoxyimi no)acetamido]-3-[(E)-2-((S)-2,2-dimethyl-5-isoxazolidinio)vinyl ]-3-cephem-4-carboxylate (YM-40220), which showed well-balanced in vitro activity and an excellent in vivo efficacy against Staphylococcus aureus Smith, as a candidate for further development.

Animals↗
PubMed1994

Intraoperative radiation therapy (IORT) for head and neck cancer.

PURPOSE: To determine the efficacy of intraoperative radiation therapy (IORT) for patients with advanced or recurrent head and neck cancer. METHODS AND MATERIALS: Intraoperative radiation therapy was given at 30 sites in 25 patients using a 6-18 MeV electron beam with or without conventional external beam irradiation. A single dose of 10-30 Gy was delivered after surgical resection. Sites treated with IORT were classified into three types after surgical resection: gross residual disease (GR, n = 7), microscopic residual disease (MR, n = 12), and close margin (CM, n = 11). Local control rate, patterns of recurrence, survival rate, and complications were analyzed. RESULTS: The 2-year cumulative local control rate within the IORT port was 54.1% for all cases, 0% for GR, 54.5% for MR, and 81.8% for CM. There were significant differences between GR and MR (p < 0.05), and GR and CM (p < 0.01). The majority of the failures inside the IORT port were associated with recurrence outside the port. Distant metastases occurred in five patients. Four of these had GR. The 2-year cumulative survival rate was 45.1% for all, 0% for GR, 33.0% for MR, and 70.0% for CM. Five patients (22%) experienced late complications. The 2-year cumulative complication rate was 32.8%. Four sites developed osteoradionecrosis and three developed carotid artery blowout. Incidence of complications increased when patients received over 20 Gy with a single dose of IORT. CONCLUSIONS: Considering both therapeutic ratio and patterns of failure, it is not suitable to treat patients with gross residual disease with IORT. We could not firmly determine the therapeutic value of IORT for patients with microscopic residual disease and close margin. For this subset, further study of moderate dose (less than 20 Gy) IORT combined with adequate postoperative irradiation is needed.

Adult↗
PubMed1994

Increased UV-induced SCEs but normal repair of DNA damage in p53-deficient mouse cells.

UV-induced sister chromatid exchanges (SCEs) in p53-deficient mouse cells were studied to obtain more evidence regarding the involvement of p53 protein in the DNA repair pathway as a checkpoint protein. After 5 J/m2 UV irradiation, mutant-type homozygous cells for p53-deficiency showed the same number of SCEs as the heterozygous and wild-type homozygous cells. In the heterozygous and wild-type homozygous cells, no further increase of SCEs was observed after 10 J/m2 UV irradiation. In contrast, in mutant-type homozygous cells about twice as many SCEs were induced by 10 J/m2 UV as by 5 J/m2 UV. In mutant-type homozygous cells, fractions of S-phase cells decreased just after 10 J/m2 UV irradiation, but recovered to higher than control levels within a short time, while in heterozygous and wild-type homozygous cells, the decrease in S-phase cells was prolonged by more than 6 hr and no increase above control levels was observed. Although no difference in UV sensitivity and repair of UV-induced DNA damage was found among the 3 genotypes, which were determined by the relative colony-forming ability after UV irradiation and removal of thymine dimers and (6-4) photoproducts from cellular DNA, our data strongly suggest an impaired checkpoint function in p53-deficient cells when DNA is damaged.

Animals↗
PubMed1994

[Role of postoperative irradiation for carcinoma of the uterine cervix: multivariate analysis of prognostic factors and patterns of failure].

We retrospectively analyzed the patterns of recurrence in 48 patients who underwent postoperative irradiation following surgery for carcinoma of the uterine cervix. The end points of pelvic control, distant metastases and disease-free survival were analyzed for parameters including FIGO stage, nodal status, degree of stromal invasion, histology and tumor size. Univariate and multivariate analyses showed that some prognostic parameters had little influence on pelvic control rate, but had a marked impact on the incidence of distant metastases and disease-free survival rate. These results suggest that postoperative irradiation improves pelvic control rate, but has little therapeutic benefit in preventing distant metastases or improving survival rate. In conclusion, we should give more consideration to adjuvant systemic therapy in addition to postoperative irradiation for high-risk patients.

Adult↗
PubMed1994

Molecular characterization and functional expression of squid retinal-binding protein. A novel species of hydrophobic ligand-binding protein.

The primary structure of squid retinal-binding protein (RALBP) was determined by cDNA and protein sequencing. Squid RALBP contains 342 amino acid residues in a single N-terminal-blocked chain with a molecular weight of 39,111. The N alpha-blocking group was identified as an acetyl moiety by mass spectrometry. The amino acid sequence revealed that the protein is highly hydrophilic and acidic, but it has several hydrophobic regions that are located mainly in the middle part of the polypeptide chain. It is also predicted that these hydrophobic regions form beta-sheet structures. The primary structure of RALBP is, however, quite distinct from those of other retinoid-binding proteins, showing that squid RALBP is a novel hydrophobic ligand-binding protein that functions in intracellular retinoid transport. Using the cloned cDNA, squid RALBP was expressed in vitro. By carrying out the translation at 20 degrees C in reticulocyte lysates, the protein having retinol binding activity was produced.

Amino Acid Sequence↗
PubMed1994

[Genetic effects of cosmic radiation in Drosophila melanogaster].

To examine possible effects of space radiation on living organism, we have analyzedtwo types of mutations, sex-linked recessive lethal mutations and somatic mutations, in fruit fly of the species Drosophila melanogaster. Drosophila strains used were wild type strains and a radiation-sensitive strain mei-41. Two different developmental stages of samples were sent into space; young adult males to analyze sex-linked recessive lethal mutations and about 30hr-old larvae to detect somatic mutations in wing epidermal cells. For wild type and mei-41 strains each, about 200 adult male flies and about 6,000 larvae were loaded on space shuttle Endeavour. The male flies returned from space were mated to virgin female flies of a tester strain, and the presence of the lethal mutations was analyzed at F2 generation. The frequencies of sex-linked recessive lethal mutations in flight groups were 2 and 3 times higher for wild type Canton-S and mei-4 1, respectively, than those in ground control groups. Most larvae sent to space emerged as adult flies within about 10 days after the landing. The presence of wing-hair somatic mutations, which give morphological change in hairs growing on the surface of wing epidermal cells, was analyzed under microscope. In wild type strain Muller-5, the frequency of wing hair mutant spots in flight group was about 1.5-fold higher than that in ground control, and in Canton-S-derived wild type strain the frequencies were similar between the two groups. By contrast, for mei-41 strain the mutation frequency was lower in flight group than in control group. The observed higher frequency of lethal mutations in the flight group might be due to a possibility that radiation effects on reproductive cells could be greatly enhanced under micro gravity. However, if this would be the case, we do not have appropriate explanation for the apparent absence of such synergistic effects on somatic wing-hair mutation system.

Abnormalities, Radiation-Induced↗
PubMed1994

Studies on beta-lactam antibiotics. IV. An improved synthesis of 3-(isothiazolylthiomethyl)cephalosporins and its application to new derivatives.

An improved synthesis and in vitro activity of cephalosporins with a (4-carboxy-3-hydroxy-5-isothiazolyl)thiomethyl group at the 3-position and its application to the preparation of new derivatives are described. These compounds showed excellent activity against Gram-negative bacteria including beta-lactamase producing strains. Among them, 2f was the most interesting because of its broad spectrum of antibacterial activity, including Gram-positive bacteria, and its outstanding inhibitory potency against Pseudomonas aeruginosa.

Animals↗
PubMed1994

[Refractive changes following cataract extraction with intraocular lens implantation].

Refractive changes after six cataract surgery procedures with intraocular lens implantation were assessed; namely, (1) 11 mm incision with running suture closure (n = 25 eyes), (2) 6.5 mm incision with running suture closure (n = 23). (3) 6.5 mm incision with horizontal suture closure (n = 21), (4) 6.5 mm incision without suture closure (n = 40), (5) 5.5 mm incision without suture closure (n = 46), and (6) 3.2 mm incision without suture closure (n = 46). The axis-based keratometric cylinder, absolute value of the induced cylinder vector, and spherical equivalent of the refractive power were analyzed up to 6 months after surgery. Refractive changes did not reach a stable state at 3 months postoperatively for the 11 mm and 6.5 mm running suture closure groups, but they stabilized at 3 months postoperatively for the 6.5 mm horizontal suture and sutureless closure groups, at 1 month postoperatively for the 5.5 mm sutureless closure group, and at 2 weeks postoperatively for the 3.2 mm sutureless closure group. It is concluded that the timing of refractive stabilization differs significantly among procedures, and smaller incisions with wound closure methods which do not exert a vertical force cause fewer postoperative refractive changes.

Aged↗
PubMed1994

Radical radiation therapy for adenocarcinoma of the uterine cervix.

PURPOSE: Analysis of the therapeutic value of radical irradiation for patients with uterine cervical adenocarcinoma with special reference to pelvic disease control. PATIENTS AND METHODS: 20 patients with uterine cervical adenocarcinoma were treated with a combination of external beam and intracavitary irradiation (four patients stage IB, one stage IIA, three stage IIB and twelve patients stage IIIB). Seven patients were treated with high dose-rate (HDR) intracavitary irradiation, eleven with low dose-rate (LDR) intracavitary irradiation and two with HDR and LDR. RESULTS: Six out of the 20 patients experienced pelvic recurrence (all stage IIIB patients). Analysis of the relation between pelvic recurrence and dose rate of intracavitary irradiation revealed that LDR showed a higher pelvic disease control rate than HDR (6/7 vs. 0/4) in stage IIIB patients. Intracavitary irradiation doses of LDR were 1.2 to 1.5 times higher than those of HDR. Three out of the 20 patients developed rectal complication grade 2 (two patients treated with HDR, one with LDR). The five-year cumulative survival rate was 67.2% for all, 100% for stage I and II, and 43.3% for stage IIIB patients. CONCLUSION: These results suggest that locally advanced uterine cervical adenocarcinoma should be treated with a higher dose using LDR intracavitary irradiation. If adequate total doses can be delivered, pelvic disease control of uterine cervical adenocarcinoma is comparable with that achieved for squamous cell carcinoma.

Adenocarcinoma↗
PubMed1993

Amino acid sequence surrounding the retinal-binding site in retinochrome of the squid, Todarodes pacificus.

Squid (Todarodes pacificus) retinochrome was reduced to N-retinyl protein with borane dimethylamine and cleaved by CNBr. The retinyl peptide was then isolated by chromatography while being monitored for absorbances at 215 and 330 nm, and the N-terminal amino acid sequence was determined to be Ser-Lys-Thr-Gly-X-Ala-Leu-Phe-Pro. This sequence was the same that we had observed at the 7th transmembrane domain of retinochrome whose structure was reported previously. During Edman degradation of the retinyl peptide, the yield of the PTH-lysine at the second cycle was lower than those of the other PTH-amino acids, proving that the lysine residue forms a Schiff's base with retinal (Lys-275 in retinochrome). The amino acid sequence surrounding the retinal-binding lysine in retinochrome greatly differed from those in a variety of known visual pigments. This fact would be associated with the difference in the photoisomerization of chromophore between retinochrome and rhodopsin. The protein structure of retinochrome is also compared with that of rhodopsin in Todarodes.

Amino Acid Sequence↗
PubMed1993

Cloning and nucleotide sequence of cDNA for rhodopsin of the squid Todarodes pacificus.

A cDNA for rhodopsin was isolated from a library constructed from poly(A)+RNA of the squid (Todarodes pacificus) retina. One positive clone with the longest insert of cDNA (3.1 kb) was selected by employing a PCR-amplified cDNA fragment as a probe. The nucleotide sequence of the cDNA revealed a single open reading frame of 1,344 bp encoding a polypeptide (M(r)49,833), which covered a complete sequence for the squid opsin. This clone had a very long 3'-non-coding region (1.7 kb) including multiple polyadenylation signals, AATAAA, resembling the clones for Todarodes retinochrome and retinal-binding protein (RALBP). The analysis of hydropathicity demonstrated the presence of seven transmembrane spanning domains, and a possible retinal-binding site, Lys-305, was found in the 7th domain. Todarodes rhodopsin contained characteristic sequences of PPQGY repeated in the C-terminal region, as reported in Loligo and octopus rhodopsins. Structural comparison of those cephalopod rhodopsins is also discussed.

Amino Acid Sequence↗
PubMed1993

The conformational analysis and photoisomerization of retinochrome analogs with polyenals.

3,7-Dimethyl-2,4,6,8,10-dodecapentaenal was synthesized for reconstitution of the retinochrome analog. Its opsin shift was 1000 cm-1 smaller than that of native retinochrome, whose chromophore contains the same number of double bonds. The conformational change from 6-s-trans to 6-s-cis, as figured in a retinal molecule, plays an important role in the formation of the retinochrome analog, based on the estimation of opsin shifts for retinal analogs locked in the 6-s conformation. Thus the conformation of the 6-7 single bond in the native retinochrome was suggested to be 6-s-cis. Analysis of the circular dichroic spectra of retinochrome analogs revealed that the 6-s conformation is independent of the appearance of the beta-band. The stereoselectivity in the photoisomerization of the retinal analogs by a retinochrome template depends on the hydrophobic binding in the region of the beta-ionone ring.

Circular Dichroism↗
PubMed1992

Immunocytochemical localization of retinal binding protein in the octopus retina: a shuttle protein for 11-cis retinal.

The cephalopod retina contains two photopigments that are spatially separated within the photoreceptors; rhodopsin, localized in the light-sensitive rhabdoms, and retinochrome, present in the myeloid bodies of the photoreceptor inner segments. In the light, the chromophore of retinochrome, all-trans retinal, is photoisomerized to 11-cis to form metaretinochrome. Metaretinochrome is believed to serve as a store for 11-cis retinal used in the regeneration or biosynthesis of rhodopsin. Previous studies suggest that a soluble retinal binding protein (RALBP) serves as a shuttle between retinochrome and rhodopsin, and, in the dark, may transport chromophore from the myeloid bodies to the rhabdoms. Our study supports this hypothesis and demonstrates that RALBP is in the correct cellular locations to function as a shuttle. Dark- and light-adapted octopus retinas were labeled with anti-RALBP using immunofluorescence and immunogold techniques. Our results showed that RALBP was distributed differently in the dark- and light-adapted retinas. Our most significant observation was that myeloid bodies from light-adapted retinas were more heavily labeled by anti-RALBP than myeloid bodies in dark-adapted retinas. The rhabdomeres, interphotoreceptor matrix, and inner limiting membrane were also labeled in both light and dark conditions. Based on these results and evidence from previous biochemical studies, we conclude that in the dark RALBP leaves the myeloid bodies and transports 11-cis retinal to the rhabdoms where chromophore exchange with metarhodopsin may occur.

Adaptation, Ocular↗