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Biomedical subjects

N Ohta

Publications and source records attributed to N Ohta.

At least 199 records · Page 11Linked to original sources

A multivariate study of the relationship between regional lymph node metastases and prognosis in patients with operable breast cancer.

In order to evaluate the prognostic importance of clinical and histological node information, we made univariate and multivariate analyses of regional lymph node metastases in 223 patients with operable breast cancer who were surgically treated from 1973 to 1985. Clinical axillary node status, histological involvement of the axillary lymph nodes, their anatomical levels and numbers, and histological involvement of the internal mammary lymph nodes were selected as evaluating prognostic factors. The histological presence or absence of axillary node involvement, especially at the distal level, proved to be the most important prognostic factor. However, neither the anatomical level nor the number of histologically involved axillary lymph nodes appeared to be an important prognostic factor. On the other hand, histological involvement of the internal mammary nodes appeared to be an important and independent prognostic factor. Therefore, we concluded that axillary lymph node dissection with a biopsy of the internal mammary nodes would provide more accurate information about the prognosis of patients with operable breast cancer.

Adenocarcinoma↗

The mechanism of photosensitization in photodynamic therapy: phosphorescence behavior of porphyrin derivatives in saline solution containing human serum albumin.

The phosphorescence properties, especially the dynamic behavior of metal free and metal complexed porphyrins, have been studied in phosphate buffered saline (PBS) containing 0-3% human serum albumin (HSA). 6,7-Bisaspartyl-2,4-bis (1-hexyloxyethyl)-deutero- porphyrin (DP) and its gallium(III), zinc(II), and indium(III) complexes are used as photosensitizers. Upon irradiation, a solution of porphyrins containing more than 0.1% HSA shows phosphorescence with a lifetime longer than 1 ms. With an increase in irradiation time, phosphorescence intensities and lifetimes of porphyrins increase, depending upon their concentrations and triplet lifetimes, and approach saturated values close to those under deaerated conditions. The experimental results may be interpreted in terms of hypoxia induced by photosensitization in a local environment surrounding the sensitizer. The hypoxia is caused by the reaction between proteins and singlet molecular oxygen generated by photosensitization of porphyrins. Phosphorescence behavior of sensitizers in HSA PBS solution gives significant information for classifying photosensitizers as to their efficacy for photodynamic therapy.

Deuteroporphyrins↗

Timing of flagellar gene expression in the Caulobacter cell cycle is determined by a transcriptional cascade of positive regulatory genes.

The Caulobacter crescentus flagellar (fla) genes are organized in a regulatory hierarchy in which genes at each level are required for expression of those at the next lower level. To determine the role of this hierarchy in the timing of fla gene expression, we have examined the organization and cell cycle regulation of genes located in the hook gene cluster. As shown here, this cluster is organized into four multicistronic transcription units flaN, flbG, flaO, and flbF that contain fla genes plus a fifth transcription unit II.1 of unknown function. Transcription unit II.1 is regulated independently of the fla gene hierarchy, and it is expressed with a unique pattern of periodicity very late in the cell cycle. The flaN, flbG, and flaO operons are all transcribed periodically, and flaO, which is near the top of the hierarchy and required in trans for the activation of flaN and flbG operons, is expressed earlier in the cell cycle than the other two transcription units. We have shown that delaying flaO transcription by fusing it to the II.1 promoter also delayed the subsequent expression of the flbG operon and the 27- and 25-kDa flagellin genes that are at the bottom of the regulatory hierarchy. Thus, the sequence and timing of fla gene expression in the cell cycle are determined in large measure by the positions of these genes in the regulatory hierarchy. These results also suggest that periodic transcription is a general feature of fla gene expression in C. crescentus.

Bacterial Proteins↗

Multiple and irreversible binding of cis-diamminedichloroplatinum(II) to human serum albumin and its effect on warfarin binding.

Irreversible bindings of cis-diamminedichloroplatinum(II) (cis-DDP) to human serum albumin (HSA) were investigated in a pH 7.4 buffer containing 0.1 M NaCl at various molar ratios (cis-DDP/HSA) up to 60 over a 14 d period (37 degrees C). The metal binding seemed to reach a plateau when incubated at less than 10 times excess of cis-DDP. As the molar ratio increased, the reaction rate was relatively fast within the first day, followed by a moderate increase in the metal binding. When incubated at 60 times excess of cis-DDP, the metal bound as much as 20 mol per mol of HSA in 14 d. Fluorescence quenching of the metal-bound protein suggested that the tryptophan residue was gradually exposed to a hydrophilic environment as the metal binding increased. Furthermore, cis-DDP cleaved disulfide bonds at the ratio of 1 mol of disulfide bond per 5.3 mol of the metal binding. It was therefore suggested that the metal binding also occurred at several sites other than the disulfide bond. Warfarin binding to the metal-bound protein, examined by fluorescence changes, also decreased with increasing metal binding or cleavage of the disulfide bonds. Thus, cis-DDP bound to multiple sites in addition to the lone sulfhydryl group (Cys-34), suggesting that massive conformational changes of the protein took place.

Cisplatin↗

[Direct priming].

The purposes of this article are to review literature on direct priming (or repetition priming) and to comment on the current literature and its perspectives. Among a number of studies concerning direct priming, two categories of studies were mainly discussed: One is concerned with longevity of priming effects, and the other is concerned with variables which influence direct priming. Most of the former research has demonstrated long-lasting priming effects, but the theoretical account remains unclear. The latter has presented a variety of inconsistent findings. Finally three directions for future research were pointed out: methodological investigation, expanding research targets, and interaction among different approaches.

Humans↗

[Cyclosporine induced nephrotoxicity and juxtaglomerular apparatus in mice].

To elucidate the relationship between Cyclosporine (Cs) induced nephrotoxicity and juxtaglomerular (JG) apparatus, we carried out biochemical and morphological experiments using mice. Adult male ICR strain mice weighing about 40 g were used. The mice were divided into 2 groups: the Cs group (Cs 50 mg/kg/day was orally given for 14 consecutive days) and the control group (olive oil for 14 days). Urine was stored for 24 hours on the day 0, 7 and 14 and urine volume and concentrations of urinary creatinine (u-Cr) and urinary potassium (u-K) were measured in each group. All the mice were sacrificed and examined on the 15th day. Concentrations of serum creatinine (s-Cr), serum potassium (s-K), plasma renin activity (PRA), plasma aldosterone (Ald) were noted in each group. The kidneys were also examined histologically with light and electron microscopes. The Cs group showed significant increases of s-K, PRA and Ald and a significant decrease of creatinine clearance compared with the control group. Histologically, the Cs group demonstrated focal vacuolar changes in the proximal tubular cells and an increase in the number of granules in the JG cells. Each granule of the Cs group was larger than that of the control group. Cs certainly stimulates the renin-angiotensin-aldosterone system and causes consequently a secondary aldosteronism.

Animals↗

[Cyclosporine induced nephrotoxicity and renal blood flow].

To elucidate the relationship between cyclosporine (Cs) nephrotoxicity and renal blood flow (RBF), we carried our experiments using rats. Adult male Wistar strain rats each weighing about 100 g were used. Rats were divided into 2 groups; the Cs group (Cs 50 mg/kg/day was intraperitoneally given for 10 consecutive days) and the control group (normal saline solution for 10 consecutive days). The renal cortical blood flow was measured in each group by electrolytic hydrogen gas clearance method. We also carried out renal angiography with barium sulfate (BaSO4). Then we measured blood vessel area/renal sagittal section area ratio and the diameter of interlobar arteries. The Cs group showed a significant decrease of renal cortical blood flow compared with the control group. On the other hand there was no significant change in renal angiogram. In conclusion, Cs decreased renal cortical blood flow. We suppose that vascular resistance increased following afferent arteriolopathy caused by Cs administration.

Animals↗

Superactive insulins.

The substitution of aspartic acid for the naturally-occurring histidine residue in position B10 in human insulin results in an insulin analogue which displays an in vitro potency 4- to 5-fold greater than the parent compound. This substitution has been introduced into six insulin analogues which, before modification, display potencies ranging from less than 0.01-fold to 3-fold relative to natural insulin. In each case, the resulting aspartic acid-substituted analogue is substantially more potent than the parent compound. Thus, it is now possible to prepare "tailor-made" insulins with enhanced potency.

Aspartic Acid↗

A novel cardio-excitatory peptide isolated from the atria of the African giant snail, Achatina fulica.

An undecapeptide which potentiates the beat of the ventricle in the African giant snail, Achatina fulica Ferussac, was purified from the atria of the snail. Its primary structure was determined to be H-Ser-Gly-Gln-Ser-Trp-Arg-Pro-Gln-Gly-Arg-Phe-NH2. This peptide was found to have excitatory actions not only on the ventricle but also on the penis retractor muscle, the buccal muscle and the identified neurons controlling the buccal muscle movement of Achatina.

Amino Acid Sequence↗

A retrospective study on the efficacy of cervical lymph node dissection in well-differentiated carcinoma of the thyroid.

The management of cervical lymph node metastases in well-differentiated carcinoma of the thyroid is controversial. In our department, from 1963 to 1972, node plucking was performed only in patients with cervical lymphadenopathy whereas, from 1973 to 1983, modified radical neck dissection was therapeutically or electively performed. In order to determine whether the more extensive dissection is adequate, a retrospective analysis was performed using two groups of patients who were managed differently with regard to the treatment of cervical lymph node metastases. From this series of 206 patients with more than five years follow-up, it was found that the rates of survival and lymph node recurrence did not differ between the two groups. However, since the well-differentiated carcinoma of the thyroid has relatively indolent biological behaviour, further long-term follow-up seems to be necessary for demonstrating the efficacy of neck dissection.

Adolescent↗

Treatment of staghorn calculi by fiberoptic transurethral nephrolithotripsy.

We treated 34 patients with staghorn calculi by fiberoptic transurethral nephrolithotripsy with a flexible nephroureteroscope and an electrohydraulic lithotriptor. Of the 34 patients 30 (88.2%) were treated successfully. There were 17 patients each with complete and partial staghorn calculi. There was no difference in the success ratio and the rate of residual fragments between the 2 groups. However, post-procedural fever, sepsis and extrapelvic extravasation were observed more frequently in patients with complete than with partial staghorn calculi. Countermeasures to avoid complications must be developed in the future. However, we believe that fiberoptic transurethral nephrolithotripsy is a safe and effective treatment for staghorn calculi. This procedure also should be recommended, as well as the combination of percutaneous nephrolithotomy and extracorporeal shock wave lithotripsy.

Adult↗

HLA-DQ-controlled T cell response to soluble egg antigen of Schistosoma japonicum in humans.

We analysed regulatory mechanisms of the human T cell response to soluble egg antigen (SEA) of Schistosoma japonicum in vitro. SEA is a crude antigen mixture containing numerous epitopes. We obtained SEA-induced T cell lines from five patients with chronic schistosomiasis japonica, and tested their proliferative response to molecular weight fractions of SEA. Although all T cell lines showed strong responses to crude SEA, there was a heterogeneity in fraction-driven responsiveness. All but one T cell line tested failed to respond to SEA fraction I (mol. wt greater than 18 kD). One patient who was typed as HLA-DQw1/w4, did not show proliferation of CD4+ T cells to fraction I; however, a fraction I-driven helper T cell response was observed when we added HU-11 monoclonal antibody specific for HLA-DQw1/w4. This indicated that the patient had helper T cells to the fraction even though their response was suppressed. Because HLA-DQ had an effect on functional expression of suppressor T cells, it was suggested that there was epitope-specific regulation of the T cell response to SEA, and HLA-DQ-controlled immune suppression might be involved in the regulatory system in human chronic schistosome infection.

Animals↗

Identification, distribution, and sequence analysis of new insertion elements in Caulobacter crescentus.

We describe two insertion elements isolated from Caulobacter crescentus that are designated IS298 and IS511. These insertion elements were cloned from spontaneous flagellar (fla) gene mutants SC298 and SC511 derived from the wild-type strain CB15 (ATCC 19089), in which they were originally identified as insertions in the flbG operon of the hook gene cluster (N. Ohta, E. Swanson, B. Ely, and A. Newton, J. Bacteriol. 158:897-904, 1984). IS298 and IS511 were each present in C. crescentus CB2 and CB15 in at least four different positions, but neither was present in strain CB13 or in several Caulobacter species examined, including C. vibrioides, C. leidyia, and C. henricii. Nucleotide sequence analysis across the chromosome-insertion element junctions showed that IS298 is located 152 base pairs (bp) upstream from the ATG translation start of the hook protein gene flaK, where it is bounded by a 4-bp direct repeat derived from the site of insertion, and that IS511 is inserted at codon 186 of the flaK coding sequence, where it is also bounded by a 4-bp direct repeat duplicated from the site of insertion. The ilvB102 mutation in strain SC125 was also shown to result from insertion sequence IS511, but no duplication of the genomic sequence was present at the insertion element junctions. IS298 contains an imperfect terminal inverted repeat 16 bp long, and IS511 contains a 32-bp inverted repeat at the termini. IS298 and IS511 are the first insertion elements described in C. crescentus.

Bacteria↗

Cloning and cell cycle-dependent expression of DNA replication gene dnaC from Caulobacter crescentus.

Chromosome replication in the asymmetrically dividing bacteria Caulobacter crescentus is discontinuous with the new, motile swarmer cell undergoing an obligatory presynthetic gap period (G1 period) of 60 min before the initiation of DNA synthesis and stalk formation. To examine the regulation of the cell division cycle at the molecular level, we have cloned the DNA chain elongation gene dnaC from a genomic DNA library constructed in cosmid vector pLAFR1-7. To ensure that the cloned sequence corresponded to dnaC, we isolated the gene by genetic complementation of the temperature-sensitive allele dnaC303 on DNA fragment that contained a Tn5 insertion element tightly linked by transduction to dnaC. The size of the dnaC gene was estimated to be 1,500 bp or less based on the pattern of complementation by subcloned restriction and BAL 31 deletion fragments. Nuclease S1 assays were used to map the transcription start site and to determine the pattern of dnaC expression in the cell cycle. Large amounts of the dnaC transcript began to accumulate only in the late G1 period of the swarmer cell and then peaked early during chromosome replication. We confirmed that the gene is periodically transcribed by monitoring the rate of beta-galactosidase synthesis directed by a dnaC promoter-lacZ fusion in a synchronous cell culture. dnaC is the first C. crescentus cell cycle gene whose regulation has been reported, and the discontinuous pattern of its expression suggests that the DNA synthetic period in these dimorphic bacteria is regulated in part by the stage-specific expression of DNA replication genes.

Bacterial Proteins↗

Synthesis of peptides related to immunoglobulin E (IgE) and the examination of their pharmacological activity.

Five kinds of oligopeptides H-Asp-Ser-Asp-OH (1), H-Asp-Gly-Lys-OH (2), H-Ser-Asp-Gly-Lys-OH (3), H-Asp-Ser-Asp-Gly-Lys-OH (4), and H-Ala-Asp-Ser-Asp-Gly-Lys-OH (5) related to immunoglobulin E (IgE) were synthesized by the conventional solution method with the objective of obtaining a new type of antiallergic agent. Their pharmacological activity was examined by measuring the inhibition of the production of IgE and relaxation of the smooth muscle contraction of rabbit aorta. H-Ala-Asp-Ser-Asp-Gly-Lys-OH (5) displayed potent inhibition against the production of IgE antibody (69.6%) and relaxation against the contraction of rabbit aorta.

Amino Acid Sequence↗