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Biomedical subjects

Y Ohashi

Publications and source records attributed to Y Ohashi.

At least 541 records · Page 30Linked to original sources
PubMed1990

Randomization in cancer clinical trials: permutation test and development of a computer program.

When analyzing cancer clinical trial data where the treatment allocation is done using dynamic balancing methods such as the minimization method for balancing the distribution of important prognostic factors in each arm, conservativeness occurs if such a randomization scheme is ignored and a simple unstratified analysis is carried out. In this paper, the above conservativeness is demonstrated by computer simulation, and the development of a computer program that carries out permutation tests of the log-rank statistics for clinical trial data where the allocation is done by the minimization method or a stratified permuted block design is introduced. We are planning to use this program in practice to supplement a usual stratified analysis and model-based methods such as the Cox regression. The most serious problem in cancer clinical trials in Japan is how to carry out the quality control or data management in trials that are initiated and conducted by researchers without support from pharmaceutical companies. In the final section of this paper, one international collaborative work for developing international guidelines on data management in clinical trials of bladder cancer is briefly introduced, and the differences between the system adopted in US/European statistical centers and the Japanese system is described.

Data Collection↗
PubMed1990

[A study on the intratubular androgen receptor in male infertility].

In order to investigate the presence of androgen insensitivity in patients with male infertility, intratubular androgen receptor (AR) was measured in patients with idiopathic oligozoospermia and azoospermia. The specimens were obtained by testicular biopsy or orchiectomy from 56 patients with oligozoospermia and 5 with azoospermia for clinical study, and 17 with varicocele, 22 with vas disorders and prostatic cancer, which had a mean germinal epithelium score count of 8.5 or greater by the method of Johnsen (JSC) for deciding the cut-off levels, as the control group. Intratubular AR was measured by a 5-point micro-receptor assay, an exchange assay with the DCC method, using 40 microliters of each sample extract and 3H-methyltrienolone as the ligand. The genital skin AR assay was also conducted simultaneously in 34 patients. The results were as follows: 1) No significant correlation was noted between intratubular ARs and genital skin ARs. 2) The maximum binding (Bmax) of AR in the total intratubular extract was intermediate between that of the cytosol fraction and the nuclear extract. 3) Significant correlation was noted between the Bmax of ARs by the micro-receptor assay and those by the conventional assay. 4) The Bmax of AR in the control group (n = 22) was 30.38 +/- 9.89 fmol/mg protein (mean +/- S.D.) and was over 11 fmol/mg protein in all cases. Therefore, 11 fmol/mg protein was decided as the cut-off level for androgen insensitivity. 5) Comparative studies were undertaken between two groups, i.e., low AR group and normal AR group, with AR as a parameter for male infertility.(ABSTRACT TRUNCATED AT 250 WORDS)

Androgens↗
PubMed1990

Oligonucleotides with pyrene fluorophore at the sugar fragment: synthesis and properties in binding to complementary polynucleotide.

Oligonucleotides with 1-pyrenylmethyl substituent at the designated sugar residue were synthesized by using 5'-dimethoxytrityl 2'-(1-pyrenylmethyl)uridine 3'-phosphorobisdiethylamidite 1. It was shown that the pyrene-oligonucleotides have enhanced affinity in binding to the complementary polynucleotide sequence. The fluorescence yield and life time of the pyrene-oligonucleotide was drastically enhanced when bound by the complementary polynucleotide.

Base Sequence↗
PubMed1990

[Combination chemotherapy of non-small cell lung cancer (NSCLC) with cisplatin (CDDP), carboquone (CQ) and prednisolone (PDN)(PPQ therapy)].

Twenty-five courses (twenty-two pts) with NSCLC have been entered in the trial evaluating the combination of CDDP 20 mg/m2 i.v. day 1, 2, 3, 4, 5, CQ 7 mg/m2 i.v. day 1, and PS 30 mg/body per os day 1, 2, 3, 4, 5, repeated every 4 weeks. Except for 1 case of early death, judgement of efficacy was possible in 24 courses, including one case of squamous cell carcinoma and 23 cases of adenocarcinoma. CR was obtained in no cases and PR in 7 cases, all of which were adenocarcinoma, with an efficacy rate of 29%. Response for primary site was obtained in 4 of 22 cases (18%). Median survival time of the 22 cases was 11.5 months. Main side effects of PPQ Therapy were symptoms in digestive organs such as nausea and loss of appetite, and bone marrow inhibition. Renal dysfunction was controllable by measures to cope with diuresis.

Adenocarcinoma↗
PubMed1990

[Herpes simplex virus latency in the cornea].

We tried to identify herpes simplex virus type 1 (HSV-1) latency in the cornea obtained at the time of penetrating keratoplasty from patients with herpetic stromal keratitis in the non-active (subsided) stage. The subject consisted of 8 patients (3 males and 5 females; average age 42.3 years) who were diagnosed as having herpetic stromal keratitis and underwent penetrating keratoplasty during a period without active lesions (subsided stage) between August, 1984 and July, 1988. No infective virus was detected in the centrifugation supernatant following each corneal homogenization. Latent virus was detected from the culture supernatant of sections of the corneas in 4 of the 8 patients. Although the ganglion trigger theory of Hill et al. has been conventionally supported as the mechanism(s) of herpetic keratitis recurrence, our results suggest that HSV-1 proliferation from latency in the cornea (peripheral tissue) might stimulate the ganglion (ganglion and skin trigger theory). The present study is the first to demonstrate HSV-1 latency in the cornea.

Adult↗
PubMed1990

The mechanism of accelerated corneal epithelial healing by human epidermal growth factor.

The effect of biosynthetic human epidermal growth factor (hEGF) was investigated on a 10-mm diameter corneal epithelial defect model in rabbits. Topical application of over 10 micrograms/ml of hEGF five times a day significantly enhanced the epithelial healing rate, in a dose-dependent manner. The maximum healing rate was observed in eyes treated with 20 micrograms/ml of hEGF (1.59 +/- 0.26 mm2/h), whereas application of less than 5 micrograms/ml of hEGF did not increase the rate of epithelial regeneration compared statistically with control vehicles (1.03 +/- 0.24 mm2/h). S-phase analysis indicated that hEGF treatment induced a high rate of epithelial replication, particularly near the limbal region, during 12 to approximately 24 hours after wounding, followed by massive cell replication from 1 mm behind the leading edge through the limbus during 24-48 hours. The change in number and distribution of S-phase cells thereafter did not essentially differ between hEGF-treated and control groups. In concordance with the S-phase analysis, there was a statistically significant increase in the DNA content in regenerating epithelium at 48 and 72 hours in the hEGF-treated group. These findings indicate that hEGF-induced acceleration of large corneal epithelial wound healing is associated with about twofold cell replication in the regenerating epithelium during 24 to approximately 48 hours after wounding. It is concluded that cell proliferation induced by hEGF, particularly that in limbal and peripheral corneal epithelial cells, may play an important role in accelerating epithelial healing.

Administration, Topical↗
PubMed1990

[Relationship between bronchial reactivity to inhaled acetylcholine, eosinophil infiltration and a widening of the intercellular space in patients with asthma].

The hypothesis that epithelial damage is related to the development of bronchial hyperreactivity has been supported by many studies. Therefore, we further examined whether or not subjects with bronchial epithelium damage showed increased bronchial responsiveness. We took biopsy specimens of the airway mucosa from 20 asthmatic patients with various degrees of disease severity and bronchial hyperreactivity by using a bronchofiber scope. The morphology of the biopsy specimens was studied by electron microscopy. Bronchoscopy was carried out after local anesthesia. Specimens of bronchial mucosa were obtained from 20 asthmatic patients (14 males, 6 females) in remission. The electronmicroscopic studies showed widening of the intercellular space between the epithelial cells and openings of the tight junctions, as well as infiltrations of eosinophils and their granules beneath and between epithelial cells. The tight junction refers to the space between epithelial cells exposed to the airway surface, leading down to the intercellular space. The intercellular space refers to the space between epithelial cells, below the tight junction. Interestingly, eosinophils and their granules were found mainly in the widened intercellular space. The incidence of a widening of the intercellular space was higher in specimens showing eosinophil infiltration than in those not showing eosinophil infiltration. A significant correlation was found between the respiratory threshold to acetylcholine and the percentage of opened tight junctions (r = -0.47, p less than 0.05) and/or the widening of the space between epithelial cells (r = -0.65, p less than 0.01). These results suggest that widening of the intercellular space may be caused by infiltrations of eosinophils and that this widening increases bronchial reactivity.

Acetylcholine↗
PubMed1990

[Lymphocyte subset change during cancer chemotherapy on patients with gastrointestinal, lung and hematopoietic malignancies].

Lymphocyte subsets measured by Ortho-mune on OKT 3, OKT 4A, OKT 8, OKT 10, OKT 11, OKM1, OKB 7, OKB 2 and OKDR were observed before and after chemotherapy on patients with gastrointestinal, lung and hematopoietic malignancies. Almost all patients showed decreased T-cell function expressed by OKT 11 or OKT 3 and suppressor, helper T-cell function expressed by OKT 8 and OKT 4A. In some patients improvement of T-cell function were observed with clinical response and in such cases life span seemed to be longer as expected, and it is supposed that during cancer chemotherapy improvement of T-cell function expressed by OKT series may be important prognostic factors.

Adult↗
PubMed1990

[Prostaglandin-E2 (PGE2) and interleukin-1 (IL-1) production from plastic-adherent peripheral blood mononuclear cells, and serum and urinary glucocorticoid levels in cancer patients treated with systemic chemotherapy--with special reference to circadian rhythm of serum cortisol levels in cancer].

Prostaglandin-E2 (PGE2) and interleukin-1 (IL-1) production from plastic-adherent peripheral blood mononuclear cells stimulated in vitro by bacterial lipopolysaccharide, serum and urinary glucocorticoid levels and the circadian rhythm of serum cortisol levels were studied for better understanding of the immunological and physiological changes produced by systemic chemotherapy in cancer patients. In one responded patient out of four, PGE2 production decreased and IL-1 production increased, whereas the serum cortisol level decreased and the urinary 17-KS excretion level increased. The circadian rhythm of the serum cortisol level was evaluated three times a day, at 7 A.M., 2 P.M. and 10 P.M. Healthy volunteers showed a peak level at 7 A.M. which decreased gradually towards evening and reached to the lowest level at 10 P.M. In contrast, cancer patients showed three additional patterns. These patterns were classified as follows, Type N showed a maximal level at 7 A.M. and minimal level at 10 P.M. as same as in healthy subjects. Type V showed a minimal level at 2 P.M. while type A showed a maximal level at this time. In type F the serum cortisol level was no greater than 1.0 micrograms/dl at any of the three time points. We examined circadian rhythm in four cancer patients treated with systemic chemotherapy. In one PR case, the circadian rhythm shifted from type V to N after the first course of therapy, then changed to type F after subsequent and another courses of the therapy. In another PR case, type N persisted during and after therapy. One MR case shifted from type A to type N. In contrast, one PD case shifted from type N to A. There results suggest that normalization of the circadian rhythm of serum cortisol was associated with the improvement in host body condition achieved by chemotherapy and that systemic chemotherapy modified the immunological and physiological state of cancer patients, as defined above. This may eventually be beneficial for patients.

Adult↗
PubMed1989

Differential expression of the IL-2 receptor subunits, p55 and p75 on various populations of primary peripheral blood mononuclear cells.

Unstimulated PBL were examined for expression of IL-2R subunits, IL-2Rp55 and IL-2Rp75, by two-color flow cytometric analyses using mAb. NKH-1+ non-T non-B cells expressed IL-2Rp75 but not IL-2Rp55, and the IL-2Rp75 sites on purified NKH-1+ cells were determined to be 1630 sites/cell by binding of 125I-labeled TU27 mAb specific for IL-2Rp75. In the CD4+ T cell population, IL-2Rp55+ cells were significantly detected, but little or marginally of the IL-2Rp75+ cells. However, IL-2Rp75+ cells were significantly detected, but little of the IL-2Rp55+ cells in the CD8+ T cell population. The IL-2Rp75 sites on CD8+ T cells were estimated at approximate 180-410 sites/cell. In the CD4+ T cells, expression of IL-2Rp75 as well as IL-2Rp55 was induced by stimulation with PHA. IL-2Rp75+ cells, but not IL-2Rp55+ cells, were also detected in the CD14+ monocyte population. In the CD20+ B cell population, a small number of IL-2Rp55+ cells was detected, but little of the IL-2Rp75+ cells.

Adult↗
PubMed1989

Presence of a p70 IL-2-binding peptide on leukemic cells from various hemopoietic lineages.

Recent studies have shown that IL-2R are composed of at least two polypeptide chains of 55 kDa (Tac or alpha-chain) and 70 to 75 kDa (p70 or beta-chain). The association of both chains forms high affinity IL-2R, whereas each chain alone binds IL-2 with a low (alpha-chain) or intermediate (beta-chain) affinity. So far, the p70 peptide has been found, in the absence of the Tac peptide, on the surface of lymphoid cells of T, B, or NK lineage. In this study, we investigated whether leukemic cells of various hemopoietic lineages expressed the p70 IL-2-binding protein. We found that both fresh leukemic cells obtained from patients, and cells from established leukemic lines of T cells, B cell, and myeloid origin constitutively expressed a p70 IL-2-binding protein on their surface, as detected by affinity cross-linking of radioiodinated IL-2. IL-2 binding and cross-linking to these cells was completely inhibited in the presence of an excess unlabeled rIL-2, but not with an anti-Tac mAb. Binding experiments on pre-B and myeloid cell lines revealed intermediate affinity IL-2R, whereas both high and intermediate affinity IL-2R were detected in T leukemic cells. The intermediate affinity binding of 125I-rIL-2 to the leukemic cell lines MOLT4 and Reh6 was inhibited by the TU27 mAb, which recognized the p75 chain of IL-2R. Moreover, the TU27 mAb could stain the K562, KM3, and MOLT4 (weakly) cell lines by indirect immunofluorescence. A high dose of rIL-2 (400 U/ml) enhanced the proliferation of cells from one out of three patients with acute myeloblastic leukemia, but it did not induce differentiation of the cells in any of three cases. Thus the finding of p70 IL-2-binding molecules on immature lymphoid and nonlymphoid hemopoietic cells should disclose new biologic functions for IL-2.

Cell Differentiation↗
PubMed1989

An experimental study of mucociliary pathology of the eustachian tube in otitis media with effusion induced by irradiation.

We have examined the function and fine structure of the mucociliary system of the eustachian tube in an experimental study of otitis media with effusion induced by X-ray irradiation. Functional examination demonstrated that the ciliary activity was diminished in such a condition, while morphological observations showed pathological findings including compound cilia, vacuolation of ciliated cells and expansion of intercellular space. These findings show that irradiation-induced otitis media with effusion results in impairment of the mucociliary system. As evidenced by these studies, the mucociliary system in the eustachian tube has an important role in the clearance of fluid produced in the tympanic cavity as well as affording improvement in this disease.

Animals↗
PubMed1989

Changes in activity of the renin-angiotensin system of the rat by induction of acute inflammation.

Angiotensinogen is the precursor of biologically active peptide angiotensin II and its hepatic synthesis is increased by the induction of acute inflammation. Studies were carried out to know whether the rise in plasma angiotensinogen is actually involved in the activity of the renin-angiotensin system during acute inflammation. The plasma level of angiotensinogen in rats was increased to 2.5 times the normal level 16 h after the induction of acute inflammation by administration of lipopolysaccharide (LPS). The plasma renin concentration (PRC) was decreased to about 40% of the normal level concomitantly with a reduction of plasma renin activity (PRA) at 4 h after LPS administration. In contrast, 16 h after LPS injection, when plasma angiotensinogen showed a high level and PRC had recovered to the normal range, PRA was increased to 1.7 times the normal level. These results indicate that acute inflammation induced by LPS causes a biphasic change in the generation of angiotensin I, i.e., an early decrease depending upon the reduction of PRC and later increase depending upon elevation of the angiotensinogen concentration.

Acute Disease↗
PubMed1989

Intraocular penetration of CT-112, an aldose reductase inhibitor, following topical instillation.

Intraocular penetration of 5-(3-ethoxy-4-pentyloxyphenyl)thiazolidine-2,4-dione (CT-112), an aldose reductase inhibitor, was investigated in rabbits following topical instillation. The concentration of CT-112 in corneal epithelium, stroma, endothelium, lens, and aqueous humor, was sequentially determined by high-performance liquid chromatography. CT-112 peaked in the corneal epithelium, stroma, endothelium and aqueous humor in 30 minutes following instillation, then gradually diminished time-dependently over a period of 24 hours. CT-112 remained detectable in the lens up to 24 hours, with a peak concentration at 2 hours after instillation.

Administration, Topical↗
PubMed1989

Structure and characterization of a cDNA clone for phenylalanine ammonia-lyase from cut-injured roots of sweet potato.

A cDNA clone for phenylalanine ammonia-lyase (PAL) induced in wounded sweet potato (Ipomoea batatas Lam.) root was obtained by immunoscreening a cDNA library. The protein produced in Escherichia coli cells containing the plasmid pPAL02 was indistinguishable from sweet potato PAL as judged by Ouchterlony double diffusion assays. The M(r) of its subunit was 77,000. The cells converted [(14)C]-l-phenylalanine into [(14)C]-t-cinnamic acid and PAL activity was detected in the homogenate of the cells. The activity was dependent on the presence of the pPAL02 plasmid DNA. The nucleotide sequence of the cDNA contained a 2121-base pair (bp) open-reading frame capable of coding for a polypeptide with 707 amino acids (M(r) 77, 137), a 22-bp 5'-noncoding region and a 207-bp 3'-noncoding region. The results suggest that the insert DNA fully encoded the amino acid sequence for sweet potato PAL that is induced by wounding. Comparison of the deduced amino acid sequence with that of a PAL cDNA fragment from Phaseolus vulgaris revealed 78.9% homology. The sequence from amino acid residues 258 to 494 was highly conserved, showing 90.7% homology.

Journal Article↗
PubMed1989

Acute effects of sulfur dioxide exposure on the middle ear mucosa.

A variety of atmospheric pollutants are known to depress mucociliary function in the respiratory system. Since the mucociliary function in the middle ear is similar, and the middle ear may be invaded by atmospheric pollutants, we decided to investigate the possible contribution of sulfur dioxide to middle ear effusion. Guinea pigs were exposed for 24 hours to 300 ppm of sulfur dioxide or air. Immediately after exposure, ciliary activity and epithelial structure were examined close to the tympanic orifice (proximal site) and more distal to it (distal site). In the animals exposed to sulfur dioxide, no effusion was found in the tympanic cavity. Ciliary activity was reduced only in the distal site. Electron microscopy demonstrated hypersecretion in the proximal site and severe pathologic changes in the distal site. Although the normally functioning cilia in the proximal site may prevent retention of surplus secretions in the ear, sulfur dioxide may promote middle ear effusion when combined with other detrimental factors, because it stimulates mucus secretion in the proximal site and impairs ciliary function in the distal site.

Air Pollution↗