Search PubMed⌕ Search

Biomedical subjects

S Yoshida

Publications and source records attributed to S Yoshida.

At least 847 records · Page 47Linked to original sources

Association of p53 protein expression with responses and survival of patients with locally advanced esophageal carcinoma treated with chemoradiotherapy.

Immunohistochemical analysis was performed to determine the clinical role of p53 mutations in patients with locally advanced esophageal carcinomas treated with concurrent chemoradiotherapy. The subjects of this study were 20 patients with previously untreated esophageal carcinomas with evidence of T4 disease and/or distant node metastases. Treatment comprised protracted 5-fluorouracil and 2-h cisplatinum infusions along with radiation treatment with a total radiation dose of 60 Gy. Tumor specimens from 18 of the 20 patients were analyzed immunohistochemically. Mutant p53 protein expression in the biopsy materials from the primary tumors was analyzed by immunohistochemical staining using a polyclonal antibody, RSP53. Expression of p53 was detected immunohistochemically in 10 (56%) of the 18 esophageal tumors, the cancer cell nuclei of which were diffusely stained. There were no significant differences between the patient backgrounds of the p53-"positive" and "negative" groups. Four (40%) of the 10 patients with p53 expression achieved overall complete remissions (CRSs) and 7 (70%) of these 10 achieved CRs of their primary tumors. In contrast, none of the 8 p53-negative patients achieved overall CRs and two (25%) achieved CRs of their primary tumors. The CR rates overall and of primary tumors tended to be higher in the p53-positive than negative group, but the differences were not significant. The survival rate for the 10 patients with p53 expression was better than that for the 8 negative ones (P>0.01): their median survival times were 12 and 4.5 months, respectively. Expression of p53 protein may be an indicator of a favorable prognosis in patients with locally advanced esophageal carcinomas treated with concurrent chemoradiotherapy.

Aged↗

Mutation analysis of gonadotropin receptor and G protein genes in various types of human ovarian tumors.

The heterotrimeric guanine-nucleotide-binding proteins (G proteins) and G protein-coupled hormone receptors including gonadotropin receptors have been suggested to play a role in ovarian tumorigenesis. However, no functional significance of gonadotropin receptors and G proteins in this process has been demonstrated. To investigate this issue, we examined point mutations in these genes in various types of ovarian tumors by polymerase chain reaction-single strand conformation polymorphism analysis and direct sequencing. Among 37 tumors (20 epitherial, 8 sex cord-stromal, and 9 germ cell tumors) and 5 carcinoma cell lines examined, no mutational sequence of G protein-interaction domains of luteinizing hormone receptor and follicle-stimulating hormone receptor, or "hot spots" of the alpha subunit of adenylyl cyclase-stimulating G protein and -inhibitory G protein was observed. Although this analysis was performed on only a limited number of tumors and cell lines, and on limited gene loci, the results suggest that mutational activation in gonadotropin receptors and G proteins is not crucial for ovarian tumorigenesis.

Female↗

A case of advanced gastric cancer complicated by severe toxicity induced by a combination of tegafur, uracil and mitomycin C, and associated with abnormal pharmacokinetics.

A 60-year-old female patient with gastric cancer and lymph node and liver metastases was treated with a combination of tegafur and uracil (UFT) (375 mg/m2/day) and mitomycin C (MMC) (5 mg/m2 once weekly). On day 15, when diarrhea appeared, chemotherapy was stopped immediately. On day 21, the WBC decreased to 900/microl and high fever developed. Despite treatment with granulocyte colony-stimulating factor and antibiotics, leukopenia persisted and the patient went into septic shock on day 26. On day 34, WBC increased to 5,400/microl and she recovered, with reduction in the size of the lymph node and liver metastases. Pharmacokinetic examination after intravenous injection of low-dose MMC (0.5 mg/m2) showed a markedly high peak plasma concentration (PPC), a large area under the time-versus-concentration curve (AUC) and reduced clearance. Similarly, oral administration of UFT (tegafur 300 mg/body) produced a relatively higher PPC and a larger AUC of 5-fluorouracil (FU). The activity of dihydropyrimidine dehydrogenase, the rate-limiting enzyme in the metabolism of FU, in peripheral mononuclear cells was within the normal range (0.265 nmol/min/mg). MMC is believed to have played a large part in inducing the severe toxicity observed in this patient. Physicians should be aware of the possibility of severe toxicity during treatment with UFT and MMC, although details of its incidence and mechanism are unclear.

Adenocarcinoma↗

Partial characterization of a 17 kDa acidic protein, EFP, induced by thiocarbamate in the early flowering phase in Asparagus seedlings.

Asparagus officinalis seedlings treated with either thiocarbamates or carbamates are induced to flower within 2-3 weeks of application. SDS-PAGE and 2-D PAGE resolutions of total soluble proteins of treated seedlings showed the accumulation of an acidic 17 kDa polypeptide. Partial amino acid sequence of the acidic protein showed homology to the wound-responsive A. officinalis PR 1, AoPR1. We named this protein EFP, early flowering protein, owing to its advanced appearance during the early transition from vegetative to floral phase. Carbamates and thiocarbamates that induced more than 80% flowering rates corresponded with increased level of EFP while compounds that are weak flower inducers showed reduced amount of EFP. The observation thus defined the correlationship of EFP to variable flowering rates.

Amino Acid Sequence↗

Co-ordination of tongue movements and peri-oral muscle activities during nutritive sucking.

A feeding bottle equipped with micro-video-camera and pressure sensor was devised to show the inside of the mouth and record sucking pressure. Activities of the temporal (TM), masseter muscle (MM), orbicular muscle of the mouth (OM) and suprahyoid muscles (SM) of 25 healthy infants were examined. Tongue and jaw movements, EMGs and sucking waves were scanned simultaneously. The tongue movements included elevation of the medial part of the tongue in a backward-moving peristaltic wave; significant correlations were found between jaw motion, tongue movement and sucking pressure. The TM, MM and OM were most active when the sucking pressure became positive and the jaw was closing, the SM showing highest activity in the negative-pressure phase. These findings show that each suckling cycle is biphasic, with sucking pressure, peri-oral muscle activities and jaw motion all closely correlated.

Electromyography↗

Increased plasma adenosine deaminase activity in the early phase of Legionella pneumophila infection in guinea pigs.

We measured adenosine deaminase (ADA) activity in a guinea pig model of Legionella pneumophila infection. Female Hartley guinea pigs were inoculated intraperitoneally with one-quarter of the LD50 dose of L. pneumophila Philadelphia-1 strain. Control groups were inoculated with clinical isolates of Staphylococcus aureus, Streptococcus pneumoniae, Haemophilus influenzae or Klebsiella pneumoniae. Each group consisted of 5 animals. ADA activity in plasma was assayed calorimetrically before and at various intervals after infection by measuring the amount of ammonia produced after adenosine was added to plasma samples. ADA activity before inoculation was 25.6 +/- 6.0 IU/1, it reached 174.4 +/- 60.0 IU/1 on day 3 after inoculation of L. pneumophila. ADA activity returned to normal levels on day 14. ADA activity did not increase significantly in guinea pigs infected with the other types of bacteria. These findings suggest that measurement of plasma ADA activity may be useful for the diagnosis of Legionella infection.

Adenosine Deaminase↗

Magnetic resonance imaging and histopathological study of brain lesions in rabbits given intravenous verotoxin 2.

When rabbits were given intravenously purified verotoxin 2 (VT2) at 5 microg/kg of body weight, they developed hemorrhagic diarrhea, flaccid paresis, an ataxic gait, an opisthotonic posture, and convulsions. To examine the effects of VT2 toxemia on the rabbit central nervous system, magnetic resonance imaging and ultrastructural studies were performed. At 24, 57, and 80 h after injection of VT2 into 12 rabbits, T2-weighted images of the central nervous system were obtained. The initial lesion was noted at 24 h in the hypothalamic areas of all experimental animals. At 57 h, the T2 value increased in the medulla of the cerebral hemisphere or the hippocampus, with a brain stem lesion in six rabbits (50%). The rabbits with the brain stem lesions, in which neurological signs were very severe, died within 6 days. Lesions in the cerebellar hemisphere and/or vermis were noted in four rabbits (33%) that survived more than 1 month. To better understand the pathogenesis of VT2 in these brain lesions, we examined the deterioration of the blood-brain barrier and cerebrospinal fluid-brain barrier by using horseradish peroxidase as a tracer. The tracer was detected by electron microscopy both in the subendothelial layer, including the basal lamina, and throughout the cytoplasm of the ependymal cell layer covering the ventricle after intravenous or intrathecal treatment with horseradish peroxidase. We also determined the localization of VT2 by immunoelectron microscopy and found that it was localized on edematous endothelial cells of capillaries, ependymal cells, and myelin sheaths. The present study suggests that VT2 was conveyed from the endothelial and ependymal cell layers and caused edematous changes in the rabbit brain.

Animals↗

Spectrum of Legionella species whose intracellular multiplication in murine macrophages is genetically controlled by Lgn1.

We examined the intracellular growth of 20 strains within six species of Legionella in thioglycolate-elicited peritoneal macrophages from A/J and C57BL/6 mice and a congenic strain derived from them (A.B Lgn1). With the exception of Legionella pneumophila Togus-1 and Bloomington-2, the intracellular growth of the 15 L. pneumophila strains tested was controlled by Lgn1. However, the intracellular growth of five Legionella species other than L. pneumophila was not under Lgn1's control.

Animals↗

Subtle pulmonary disease: detection with computed radiography versus conventional chest radiography.

PURPOSE: To determine the diagnostic efficacy of hard- and soft-copy computed radiographic (CR) images versus conventional screen-film images of the chest in the detection of subtle pulmonary abnormalities. MATERIALS AND METHODS: Twenty observes compared 87 hard-copy and soft-copy CR images with hard-copy screen-film images. Of 87 test images, 45 (including two identical sets of 12 images to test intra-observer variability) were abnormal and 42 (including two identical sets of 12 images) were normal. Of the 45 abnormal images, 15 (including two sets of four identical images) showed subtle abnormalities, 15 (including two sets of four identical images) showed mild abnormalities, and 15 (including two sets of four identical images) showed obvious abnormalities. Soft-copy viewing provided three differently processed images of every radiograph. RESULTS: No statistically significant differences in receiver operating characteristic analyses were found among hard-copy screen-film images, hard-copy CR images, and soft-copy CR images, even in the group with subtle interstitial abnormalities. CONCLUSION: Hard-copy and soft-copy chest CR images are acceptable and available in place of screen-film images for primary interpretation of subtle interstitial lung diseases.

Adult↗

A variant of adenomatous goiter with characteristic histology and possible hereditary thyroglobulin abnormality.

A variant type of adenomatous goiter was identified in 24 of 2160 patients with adenomatous goiter who underwent thyroidectomy. The characteristics of the thyroid gland in these 24 patients included large goiter, small follicles, scant colloid, and columnar follicular cells containing yellow-green granules on hematoxylin-eosin staining. The thyroid gland was slightly orange-red, and electron microscopic examination showed abundant lysosomes with colloid droplets. When comparing the features of this group with those of 24 patients with common adenomatous goiter, the incidence of familial predisposition to thyroid diseases in the former group was higher. The age at the time of detection of goiter was lower, i.e. 17 +/- 15 vs. 44 +/- 17 yr (P < 0.001, variant type vs. common type), the serum total T4 concentrations were lower (84 +/- 21 vs. 103 +/- 18 nmol/L; P < 0.01), and the serum TSH concentrations were higher (2.4 +/- 2.1 vs. 1.0 +/- 0.9 mU/L; P < 0.01). Thyroid radioiodine uptake was remarkably increased (49 +/- 22 vs. 16 +/- 9%; P < 0.001), and lower levels of serum thyroglobulin were noted (33 +/- 51 vs. 484 +/- 603 micrograms/L; P < 0.01). The thyroglobulin content was low in the thyroid gland studied. The data suggest that the etiology of this variant type of goiter is a hereditary abnormality in thyroglobulin synthesis, and this type of goiter may be distinguished from common adenomatous goiter by the characteristic morphology of the thyroid gland in addition to clinical findings.

Adult↗

Posterior end mark, a novel maternal gene encoding a localized factor in the ascidian embryo.

Ascidian embryogenesis is regarded as a typical 'mosaic' type. Recent studies have provided convincing evidence that components of the posterior-vegetal cytoplasm of fertilized eggs are responsible for establishment of the anteroposterior axis of the embryo. We report here isolation and characterization of a novel maternal gene, posterior end mark (pem). After fertilization, the pem transcript is concentrated in the posterior-vegetal cytoplasm of the egg and later marks the posterior end of developing ascidian embryos. Despite its conspicuous localization pattern, the predicted PEM protein shows no significant homology to known proteins. Overexpression of this gene by microinjection of synthesized pem mRNA into fertilized eggs results in development of tadpole larvae with deficiency of the anteriormost adhesive organ, dorsal brain and sensory pigment-cells. Lineage tracing analysis revealed that the anterior epidermis and dorsal neuronal cells were translocated posteriorly into the tail region, suggesting that this gene plays a role in establishment of anterior and dorsal patterning of the embryo. The ascidian tadpole is regarded as a prototype of vertebrates, implying a similar function of pem in vertebrate embryogenesis.

Amino Acid Sequence↗

Non-glutamate type pyrrolo[2,3-d]pyrimidine antifolates. II. Synthesis and antitumor activity of N5-substituted glutamine analogs.

The glutamic acid moiety of N-[4-[3-(2,4-diamino-7H-pyrrolo[2, 3-d]pyrimidin-5-yl)propyl]benzoyl]-L-glutamic acid (1b, TNP-351) and related compounds was replaced with some N5-substituted glutamines. Antifolates (4A-S) were effectively prepared by coupling pyrrolo[2,3-d]pyrimidine carboxylic acids (11a, b) with some properly protected N5-substituted glutamine derivatives (10A-S), which were prepared by coupling Boc-Glu-OMe (7) with various amines (8A-S) using a suitable condensing reagent, followed by hydrolysis. The inhibitory effects of the resulting products on dihydrofolate reductase (DHFR), thymidylate synthetase (TS) and the growth of murine fibrosarcoma Meth A cells in culture were examined. All N5-substituted glutamine analogs (4A-S) inhibited DHFR much more strongly than TNP-351 and some analogs exhibited the same potent growth inhibition of Meth A cells as TNP-351. Some typical analogs (4Bb, 4Db, 4F, 4Oa) were also examined for inhibitory effects on the growth of methotrexate (MTX)-resistant human CCRF-CEM cells in culture and for in vivo antitumor activities against murine leukemia and solid tumors. MTX-resistant cells, with a defect in transport and decreased polyglutamylation activity, showed little cross resistance to the analog (4Oa) having a tetrazole moiety as a substituent of glutamine, which exhibited potent antitumor activities. These results demonstrate that the antifolate analogs (4) with N5-substituted glutamine in place of glutamic acid are novel potent DHFR inhibitors with activity against MTX-resistant tumors. The potent antitumor activity of these analogs (4) may result from their effective uptake via reduced folate carrier in combination with their potent inhibition of DHFR.

Animals↗

Vasospastic angina in a patient with Fabry's disease who showed normal coronary angiographic findings.

It has been reported that coronary diseases in patients with Fabry's disease are induced by deposits in endothelial cells and coronary smooth muscle cells. Most of those are ischemia due to stenosis. This report describes a case of patient with Fabry's disease who showed severe vasospasms without coronary artery stenosis during acetylcholine loaded coronary angiography. In this case, a myocardial biopsy revealed that the deposits in the endothelial cells of the myocardial capillaries were lamellated appearance. Recently, it is reported that endothelial cell damage could be an important cause of coronary vasospasm. This case suggests that the some sort of functional disorder was induced by glyco-sphingolipid deposits in the coronary endothelial cells, and that this might have led to coronary artery spasms without the organic stenosis of coronary arteries.

Adult↗

Water uptake and growth of cucumber plants (Cucumis sativus L.) under control of dissolved O2 concentration in hydroponics.

Dissolved O2 concentration ([O2]) in nutrient solution was controlled at 0.01, 0.10 and 0.20 mM with accuracy of +/- 0.005 mM in a newly developed hydroponic system, and the effects of [O2] on water uptake and growth of cucumber plants (Cucumis sativus L.) were analyzed. For evaluating water uptake rate under the control of [O2], water flux at the stem base was measured on-line with +/-5% in accuracy, 1 mg s-1 in resolution and 1 min in time constant by heat flux control (HFC) method. Water uptake rate was drastically increased by lighting to the plant at each [O2], and water uptake per day was depressed in proportion to decrease in [O2]. In the plants grown for 10 days, leaf area, fresh weight and dry weight of leaves decreased at lower [O2], while stem length and number of leaves were scarcely affected. These facts suggest that membrane permeability of root cells reduces at lower [O2] through respiration-dependent processes, and growth is inhibited through leaf turgor loss caused by the depressed water uptake of roots in O2-deficient nutrient solution in hydroponics.

Biomass↗