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Biomedical subjects

Y Ohashi

Publications and source records attributed to Y Ohashi.

At least 433 records · Page 24Linked to original sources

Time dependency of the influence of prognostic factors on relapse in breast cancer.

BACKGROUND: A number of factors concerning the prognosis of cancer patients have been reported, but the evaluation of individual factors is not always consistent. The author considered that the discrepancies may lie in part in that factors may have a changing influence on relapse with time. The present study was intended to reveal the phenomenon and its clinical significance in patients with breast cancer. METHODS: Eleven pathological prognostic factors in 462 patients with primary breast cancer were analysed with special reference to the influence on relapse and its changes with time. The Cox regression analysis was performed for whole and three stratified non-overlapping observation period (within 2, 2-5 and 5 years more), using factors including extent of nodal involvement (N), nuclear grade (NG), tumor infiltrating lymphocytes (TIL), tumor size, fat infiltration (F) and others. RESULTS: Cox regression analysis for whole observation period showed N followed by NG, TIL, F and others as the most important factors on relapse. But the analysis performed for 3 stratified intervals revealed that the influence on relapse decreased with time for N and NG, but tended to increase with time for F. The suppressive effect of TIL on relapse was not evident up to 2 years but was significantly emphasized after 2 years postoperatively. CONCLUSIONS: In conclusion, a distinct time-dependency with varied patterns was found in the influence of some prognostic factors on relapse, which implies the assessment of prognostic factors may vary according to the length of the observation period.

Adipose Tissue↗

Activation of nitric oxide synthase from cultured aortic endothelial cells by phospholipids.

Nitric oxide is a recently discovered biomolecule with a broad range of actions and synthesized by nitric oxide synthases. We investigated effects of lipids on particulate nitric oxide synthase purified from cultured bovine aortic endothelial cells by monitoring the conversion of L-[3H]arginine to L-[3H]citrulline. Phosphatidylcholine, lysophosphatidylcholine, and phosphatidylethanolamine dose-dependently enhanced the enzyme activity up to 3 fold in the presence of Ca2+, calmodulin, NADPH, FAD, and (6R)-5,6,7,8-tetrahydrobiopterin. These phospholipids increased the Vmax of nitric oxide synthase without altering the Km for L-arginine and the affinities for Ca2+ and calmodulin. These findings suggest that phospholipids play an important role in modulating endothelial nitric oxide synthase activity.

Amino Acid Oxidoreductases↗

[Analysis of corticoids in adrenal glands by high performance liquid chromatography (HPLC)].

The HPLC system was used to separate and measure 10 kinds of corticoids in adrenal tissues. Calibration curves were drawn as straight lines that ranged from 1.25 to 20ng, or 1.25 to 200ng by peak area calculated with the chromatointegrator. The samples for the assay were extracted from homogenized tissues and treated with methanol to remove non-steroidal contaminants which may interfere with the ultraviolet absorption monitor. The recovery rate during the assay procedure was calculated using testosterone as the internal standard, because testosterone was not detected in any adrenal tissue examined in the present study. Contents of corticoids were measured in normal adrenal glands obtained during radical nephrectomy for renal cancer and in functioning adrenal adenomas. Steroid levels in the adrenal glands and tumors have been measured by radioimmunoassay until now, and the data obtained in the present study were compared with those in previous reports. Main steroids in normal adrenals were cortisol (F) and corticosterone (B), and there were certain amounts of 11-deoxycortisol (S), 11-deoxycorticosterone (DOC) and precursor steroids. 11 beta-hydroxy-androstenedione was the main androgen in the adrenal gland. Mineralocorticoids other than B and DOC were very low in the normal adrenals. There was a certain balance between the production of cortisol and corticosterone in normal adrenals. In functioning adenomas, the levels of F, B and aldosterone, and F to B ratios (F/B) varied according to their biological features. Although with the HPLC system it was possible to obtain the production balance of each steroid clearly in the chromatogram, we could not detect the delta 5-3 hydroxysteroids such as pregnenolone and dehydroepiandrosterone using the ultraviolet absorption monitor.

Adrenal Cortex Hormones↗

Familial genetic defect in a case of leukocyte adhesion deficiency.

Leukocyte adhesion deficiency (LAD) is an inherited immunodeficiency disorder caused by CD18 subunit abnormality dependent defective expression of beta 2 integrins on the surface of leukocytes. On analysis of the CD18 molecular defect in a female Japanese patient with a severe deficiency LAD phenotype, neither CD11a nor CD18 molecules could be detected on the patient's EBV-transformed B lymphoblastoid cell line. The mRNA of the patient's B cells was normal in size, but was diminished in quantity, to approximately half normal levels. Sequencing of the CD18 cDNA of the patient revealed a C605 to T transition, resulting in a Pro178-->Leu substitution. This was heterozygous in the genomic DNA, and shown to be of maternal origin by family study. Only a few transcripts from the other allele without the Pro178-->Leu mutation were detectable. Northern blot analysis revealed reduced CD18 mRNA levels, not only in the patient, but also in the father and brother. These results indicate that our case is a compound heterozygote with two different mutant alleles: one causing a single amino acid substitution and the other causing defective expression of mRNA.

Amino Acid Sequence↗

Defective mononuclear cell antibody-dependent cellular cytotoxicity (ADCC) in patients with leukocyte adhesion deficiency emphasizing on different CD11/CD18 requirement of Fc gamma RI versus Fc gamma RII in ADCC.

The defective antibody-dependent cellular cytotoxicity (ADCC) of mononuclear cells (MNC) from patients with leukocyte adhesion deficiency (LAD), beta 2 integrins (CD11a-c/CD18) deficiency was shown. LAD patients completely failed to generate MNC-ADCC against sheep red blood cells (SRBC) sensitized with murine (m) IgG2b, but had diminished but significant cytolysis against mIgG2a-SRBC, suggesting that the CD11/CD18 requirement of Fc gamma RI is different from that of Fc gamma RII in MNC-ADCC. Blocking experiments with monoclonal antibodies (mAb) against individual subunits of CD11/CD18 revealed that anti-CD18 mAb almost completely inhibited mIgG2b-mediated ADCC by normal monocytes, but only partially inhibited mIgG2a-mediated ADCC. These data may confirm the evidence that Fc gamma RII-mediated ADCC absolutely requires CD11/CD18 but Fc gamma RI-mediated ADCC does not. Among subunits of CD11/CD18, appeared to be most involved in lysis of sensitized SRBC.

Antibody-Dependent Cell Cytotoxicity↗

Influenza A modification of endotoxin-induced otitis media with effusion in the guinea pig.

A total of 120 Hartley strain guinea pigs were used to investigate the possible role of influenza A in endotoxin-induced otitis media with effusion. Intratympanic inoculation of 0.2 ml physiologic saline solution containing 10(4) plaque-forming units (PFU)/ml of influenza A suspension or 100 ng/ml lipopolysaccharide failed to induce either middle ear effusions or mucociliary pathologies in the tubotympanum. In contrast, intratympanic inoculation 100 ng/ml endotoxin resulted in prolonged mucociliary dysfunction and middle ear effusions when 0.2 ml 10(4) PFU/ml of influenza A was inoculated in the tympanic cavity. The inference is drawn that an influenza A infection might predispose the middle ear to endotoxin-induced otitis media with effusion.

Animals↗

Sequence-specific binding of protein factors to two independent promoter regions of the acidic tobacco pathogenesis-related-1 protein gene (PR-1).

Gel shift mobility analysis, using the proximal 0.3 kb fragment of the tobacco pathogenesis-related protein 1a gene (PR-1a) and nuclear extracts from healthy Samsun NN tobacco leaves, which do not produce PR-1 proteins, showed a broad shifted signal with low mobility. This signal was not detected with nuclear proteins from the interspecific hybrid of Nicotiana glutinosa x Nicotiana debneyi, which constitutively produces the PR-1a protein. Similar shifted signals were detected with both proximal and distal regions of the 0.3 kb fragment using nuclear proteins from healthy Samsun NN tobacco, but not with proteins from the interspecific hybrid. Further experiments, performed using 5' or 3' truncated fragments of the 0.3 kb fragment, identified two independent binding sites: a distal site between -179 and -168 bp from the transcription start site, and a proximal site between -61 and -37 bp. Footprint analysis revealed two protected sequences, a distal region between -184 and -172 bp, and a proximal region between -68 and -51 bp. These results indicate the presence of regulatory factor(s) for expression of the acidic PR-1a gene. The possibility of negative regulation of the gene is discussed.

Base Sequence↗

Distribution of epidermal growth factor in rat ocular and periocular tissues.

Using a sensitive radioimmunoassay (RIA) specific for rat epidermal growth factor (rEGF), we investigated the presence of rEGF in a variety of rat ocular and periocular tissues. Immunoreactive rEGF (IR-rEGF) was present in tear fluids (25.5 +/- 5.8 ng/ml), exorbital lacrimal gland (6.73 ng/g wet weight), intraorbital lacrimal gland (2.80 ng/g wet weight), Harderian gland (1.90 ng/g wet weight), and conjunctiva (0.16 ng/g wet weight). EGF was not detectable in aqueous humor, cornea, iris and ciliary body, lens, or the posterior part of the globe (retina, choroid, and vitreous body). Gel exclusion chromatography and reverse-phase high-performance liquid chromatography revealed that IR-rEGF in the above ocular fluids and tissues was indistinguishable from standard rEGF. Using enzyme-linked immunohistochemistry, rEGF was demonstrated to be localized in the duct epithelial cells of lacrimal glands. These findings reveal that EGF is preferentially localized in the ocular surface and lacrimal apparatus.

Animals↗

Partial monosomy 5p and partial trisomy 5q due to paternal pericentric inversion of chromosome 5.

A male infant with partial monosomy 5p and partial trisomy 5q due to paternal pericentric inversion of chromosome 5 (46,XY,rec(5), dup q,inv(5)(p15.1q35.1)pat) is reported together with the oral findings. The phenotype was chiefly the cri-du-chat syndrome. Severe retardation of mental and motor development, microencephaly, cardiac malformation, crying and facial appearance unique to the cri-du-chat syndrome were observed. Perioral and intraoral findings included thin upper lip, down-turning corners of mouth, micrognathia, shallow palate, and cleft of soft palate. Anterior deciduous teeth were small and canine deciduous teeth were conic. The row of deciduous teeth showed a flat arch-like shape that was very wide but short in length. No abnormality was noted in the number of deciduous teeth or the timing of eruption.

Adult↗

Sectorization of the central 30 degrees visual field in glaucoma.

PURPOSE: To determine an optimal sector pattern of the central 30 degrees visual field in glaucoma by mathematically analyzing the visual field data of primary open-angle glaucoma (POAG) without any assumption such as the retinal nerve fiber layer anatomy. METHODS: One hundred three visual fields of the 30-2 program of the Humphrey Field Analyzer obtained from 103 POAG patients of early to moderately advanced stage were included. Based on the interpoint correlation of deviation of the measured threshold value from the age-corrected normal reference value (total deviation, STATPAC), test points of the 30-2 program were mathematically clustered using the VARCLUS procedure, a new clustering algorithm developed by the SAS Institute. The sector value, which summarizes the visual field performance of the clustered test points (sector), also was calculated. RESULTS: The 30 degrees central visual field was divided into 15 sectors consisting of at least 3 points. The distribution of sectors was compatible with the projection of nerve fiber layers. There was no sector extending over the horizontal meridian, but the sector pattern was not completely symmetrical around it. Linear regression analysis of the sector values against the mean deviation (STATPAC) suggested that the index is useful in following visual field performance of each sector. CONCLUSION: The sector pattern and sector values obtained were considered useful in studying the visual field data of glaucoma.

Algorithms↗

Nitrogen dioxide-induced eosinophilia and mucosal injury in the trachea of the guinea pig.

Nitrogen dioxide exposure-induced mucosal pathology of the guinea pig trachea was studied. Exposure to 3 or 9 ppm of nitrogen dioxide for 6 h a day, 6 times weekly for 2 weeks resulted in decreased ciliary activity as well as a dramatic eosinophil accumulation to the epithelium and submucosal layer. Especially exposure to 9 ppm of nitrogen dioxide induced epithelial injury through the activation of eosinophils accumulated in the tracheal mucosa. The epithelial damage induced by nitrogen dioxide could lead to hyperresponsiveness and prolonged allergic inflammation. Our study suggests that environmental nitrogen dioxide could contribute to the hyperresponsiveness and could most probably be involved in the development and chronicity of airway allergic disorders.

Animals↗

Hepatitis in an adult with rubella.

Rubella was accompanied by hepatic dysfunction in a 28-year-old male. Serum aminotransferase levels were moderately elevated and LDH markedly increased, especially LDH isoenzyme 5, whereas total bilirubin and ALP remained almost normal. GOT, GPT and LDH levels were completely normalized by the 21st hospital day. Paired antibody titers of viruses which may cause hepatitis, other than rubella, were of no significance. Laparoscopy showed enlarged, red liver. Histologic and electron microscopic findings of the liver were consistent with acute hepatitis. Hepatic damage with rubella is rare, and it is possible that the hepatic dysfunction seen in adult rubella may be mediated by an immunopathologic mechanism.

Acute Disease↗

[Do blood glucose levels in the elderly have different metabolic significance than in non-elderly subjects?].

Diagnostic criteria of diabetes mellitus in elderly people are still controversial. The major questions are whether (1) effects of hyperglycemia in generating diabetic complications are the same as in younger diabetics, (2) too many diabetics might be diagnosed in the elderly by the criteria proposed by WHO and Japan Diabetes Society. To answer these questions, we carried out two studies. Blood glucose data were collected from population-based studies and from voluntary health check-up studies. Fasting blood glucose values were classified by sex and the age (-49, 50-64, 65-years old). Population-based studies showed no age-dependent change in blood glucose. However, data from health check-up studies showed an increase in median values from the group aged 50-64 and the 65 and older group. Two-hour values after glucose tolerance tests were classified by age and the fasting blood glucose (-99, 100-119, 120-139, and 140- mg/dl). The eldest and 140- mg/dl group showed the highest 2-hour values. Effects of hyperglycemia on the appearance of diabetic complications were studied in patients being follow-up in three diabetes clinics. Patients who has a history of one year or less and without any retinopathy on the first visit to the clinic were registered. Data were analyzed by the Kaplan-Meier method and the appearance of retinopathy was used as the end point. There were no difference in the rate of appearance of retinopathy between the age groups (-49, 50-64 and 65-years old). No age effect on the hyperglycemia-dependent appearance of retinopathy could be observed.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

[Assessment of the quality of life of prostate cancer patients].

Assessing the QOL in cancer clinical trials is becoming increasingly important. However, a suitable device of assessment of QOL has not been developed yet for prostate cancer patients in Japan. We tried to assess the QOL of prostate cancer patients using the EORTC questionnaire translated in Japanese, and examined its validity and reliability. Thirty-six patients filled in a questionnaire. The reliability of this device was confirmed by the results of test-retest reproducibility. Good correlation was shown between the results and patients performance status, and between the results and clinical stages, which support the validity of the device. As for the results of assessment of QOL, these patients were severely damaged in sexuality. Those factors of functional status, physical symptoms and fatigue/malaise were closely related to disease activity and clinical stage.

Aged↗

[Clinical results of radical surgery for prostate cancer].

We reported the clinical results of radical surgeries for 44 patients with prostate cancer performed between November 1984 and December 1992. The patients were aged from 57 to 79-year-old (mean 67.2) and classified as clinical stage A2 (6 cases), B1 (7), B2 (12), C (16) and D1 (3) respectively. Radical prostatectomy was performed in 42 cases and radical cystoprostatectomy with urinary diversion in 2 patients, and thirty-nine of 44 cases underwent endocrine or chemoendocrine therapies prior to the surgeries. In all patients with stage A2-B1, the operations were curative, on the other hand, more than 80% of clinical stage B2 patients had pT3 tumors and 33.3% of them had lymph node involvements. With regard to stage C patients, the incidence of lymph node metastasis and positive margin was more frequent. Postoperative adjuvant therapies were added to the patients with pT3,4 tumors and nodal involvements. Patients without residual tumors (n = 20) remained disease-free for 8-89 months (mean 32.8). Of 24 patients who had incomplete resection of tumors, 2 died of other diseases, other 2 were alive recurrent and 20 were alive free from disease for 3-99 months (mean 33.8). The surgical indication for low-stage (A2-B2) prostate cancer has been widely accepted, however that for high-stage cancer (C,D1) has remained controversial. It was our belief that radical surgeries for high-stage cancer could become a potentially curative therapeutic modality in combination with pre- and post-operative adjuvant therapies.

Aged↗

[Clinical study of recombinant human granulocyte-colony stimulating factor (KW-2228) in pediatric field. 1. Effectiveness on neutropenia by various causes and safety].

The effect of KW-2228, a derivative of recombinant human granulocyte colony stimulating factor, on neutropenia in children was studied in 23 cases of aplastic anemia, 13 cases of chronic benign neutropenia, 6 cases of congenital neutropenia (Kostmann type), 2 cases of cyclic neutropenia, 2 cases associated with glycogenosis type Ib and 1 cases associated with immune deficiency. KW-2228 was administered at 1-8 micrograms/kg subcutaneously and at 2-16 micrograms/kg intravenously. As a principle, the administration was started at low doses and continued for 7-28 days increasing the doses in the cases who didn't respond to the treatment well. The response rate of all the cases by the physicians in charge was 81. 8% (36/44). The mean absolute neutrophil count was increased from 304 to 1,300/microliters in aplastic anemia, from 204 to 3,027/microliters in chronic benign type, from 125 to 2,193/microliters in Kostmann type, and from 360 to 2,007 microliters in others. KW-2228 did not induce any noteworthy serious side effects. These results indicated that KW-2228 is a useful drug to treat neutropenia in children.

Adolescent↗

[Clinical study of recombinant human granulocyte-colony stimulating factor (KW-2228) in pediatric field. 2. Effectiveness on neutropenia associated with administration of anticancer agent and safety].

The effect of KW-2228, a derivative of recombinant human granulocyte colony stimulating factor, on neutropenia associated with chemotherapy was studied in pediatric patients with malignant tumor. To patients repeatedly treated with the same chemotherapy, KW-2228 was administered subcutaneously at 1 microgram/kg or intravenously at 2 micrograms/kg once a day in the 2nd course of the chemotherapy. During the administration term of KW-2228, the nadir of neutrophils went up, and the duration of neutrophil count under 500/microliters as well as the interval for recovery of the count to 500/microliters were remarkably shortened, compared with those during the observation term. Further, the duration of fever in patients and the administration days of antibacterial agent were also reduced. The effective rate judged by attending doctors was as high as 78.9%, consisting of 83.3% in 42 cases of subcutaneous administration and 73.5% in 34 cases of intravenous administration. Side effects such as slight skeletal pain and slight fever in one case each (2.3% in total) were improved without treatment. It is concluded that KW-2228 may be a useful drug for treatment of neutropenia associated with chemotherapy in pediatric patients with malignant tumor.

Adolescent↗