Biomedical subjects

M Nagata

Publications and source records attributed to M Nagata.

At least 253 records · Page 14Linked to original sources

PubMed1996

[Reproductive and developmental toxicity studies of calcipotriol (MC903): (3)--A teratogenicity study in rabbits by subcutaneous administration].

Teratogenicity of calcipotriol (MC903), an anti-psoriasic agent, was studied. MC903 at doses of 0.1, 0.5, 1, 2.5 and 5 micrograms/kg/day was subcutaneously administered to pregnant Std:NZW rabbits from day 6 to 18 of gestation. 1. A decrease in locomotor activity was observed in the group administered MC903 5 micrograms/kg/day. Food consumption and body weight gain decreased dose-dependently in groups administered MC903 1 microgram/kg/day or more. Granular whitish kidneys were observed in groups administered MC903 2.5 and 5 micrograms/kg/day. Rough and whitish aorta were noted in groups administered MC903 1 microgram/kg/day or more. 2. Significant fetotoxicity was not induced by administration of MC903 up to 0.5 microgram/kg/day. 3. On the basis of results obtained in the present study, it is considered that no-toxic dose level of MC903 is 0.5 microgram/kg/day for pregnant animals and fetuses.

Abnormalities, Drug-Induced↗

PubMed1996

[Reproductive and developmental toxicity studies of calcipotriol (MC903): (4)--A perinatal and postnatal study in rats by subcutaneous administration].

Perinatal and postnatal toxicity of calcipotriol (MC903), an antipsoriasic agent, was studied. MC903 at doses of 6.25, 12.5 and 25 micrograms/kg/day were subcutaneously administered to pregnant Slc:SD rats from day 17 of gestation to day 21 after delivery. 1. Administration of MC903 at any doses did not adversely affect pregnant animals in regard to gestation, delivery and maternal behavior. In dams administered MC903 25 micrograms/kg/day, food consumption and body weight gain were marginally lower than those of control animals during lactation period. 2. In group administered MC903 25 micrograms/kg/day, body weight gain in F1 offsprings was significantly lower as compared with those of control group. The drug did not have any adverse effects on the postnatal development of the offspring such as differentiation, functional development, emotionality, motor ability, learning ability or reproductive performance. 3. On the basis of results obtained in the present study, it is considered that the no-toxic dose level for general toxicity and reproduction in the dams was estimated to be 12.5 and 25 micrograms/kg/day, respectively, the no-toxic dose levels in the offspring was also estimated to be 12.5 micrograms/kg/day.

Animals↗

PubMed1996

[An antigenicity study of calcipotriol (MC903)].

Antigenicity of calcipotriol (MC903), an anti-psoriasic agent, was investigated in mice and guinea-pigs. 1. In mice, MC903 administered alone or with an adjuvant (Alum) did not result in the production of MC903-specific IgE antibody. 2. In guinea-pigs sensitized with MC903 alone or plus an adjuvant (FCA), systemic anaphylaxis was not induced by challenging with MC903. IgG1 antibody in MC903-sensitized guinea-pigs was not detected by the 4-hr PCA test. 3. Ovalbumin induced the production of ovalbumin-specific IgE antibody in mice, and ovalbumin-specific IgG1 antibody in guinea-pigs. Intense systemic anaphylaxis in the ovalbumin-sensitized guinea-pigs was induced by challenging with ovalbumin. 4. Results obtained in the present study suggest that MC903 does not induce the production of IgE antibody in mouse, and IgG1 antibody in guinea-pig, and in MC903-sensitized guinea-pig systemic anaphylaxis is not induced by challenging with MC903.

Anaphylaxis↗

PubMed1996

[A mutagenicity study of calcipotriol (MC903)].

Calcipotriol (MC903), an anti-psoriasic agent, was examined for mutagenicity in the reverse mutation test and the chromosomal aberration test in vitro, and the micronucleus test in Slc:ddY mice. 1. In the reverse mutation test using Salmonella typhimurium (TA100, TA1535, TA98, TA1537) and Escherichia coli (WP2uvrA), MC903 did not significantly increase revertant colonies in any of the test strains with or without metabolic system. 2. In the chromosomal aberration test with a Chinese hamster fibroblast cell line (CHL), MC903 did not significantly increase aberrant cells in the direct method or in the activation method. 3. In the micronucleus test with male mice, MC903 did not significantly increase in the number of polychromatic erythrocytes with micronuclei in the bone marrow. These results suggest that MC903 has no mutagenic as well as clastogenic effects under the present experimental condition.

Animals↗

PubMed1996

[Dermatotoxicity studies of calcipotriol (MC903) ointment--primary skin irritation, skin sensitization, phototoxicity and skin photosensitization].

MC903 ointment was studied on primary skin irritation in rabbits and skin sensitization, skin photosensitization and phototoxicity in guinea-pigs. 1. MC903 ointment, ointment base and deteriorated MC903 ointment induced erythematous changes in rabbit skin. These erythematous changes were not so serious, and they were classified as a mild irritant. 2. MC903 ointment was almost negative in skin sensitization study. 3. MC903 ointment has no skin phototoxicity in guinea-pigs. 4. MC903 ointment has no skin photosensitizing activity in guinea-pigs.

Animals↗

PubMed1996

[Study of malignant lymphoma in the parotid gland region].

Malignant lymphomas arising in the salivary glands are very uncommon. The vast majority of these lesions are classified as extranodal non-Hodgkin's lymphoma. Clinical presentation, management, histopathology, and outcome in 11 cases of non-Hodgkin's lymphomas of the parotid gland region were reviewed. The ages of the patients ranged from 25 to 80 years (average 56.0 years) and the male to female ratio was 5:6. Presenting symptoms were painless masses (10 cases) and a painful mass (1 case) in the parotid gland region. None of the patients had facial nerve paralysis. It seems to be difficult to diagnose malignant lymphomas of the salivary glands preoperatively, because an open biopsy of the salivary glands is generally contraindicated. We failed to diagnose malignant lymphoma in the parotid gland preoperatively. The clinical stages were stage I in 5 cases, stage II in 5 cases, and stage III in 1 case. There was no patient with stage IV. Three of the stage I tumors were diagnosed as MALT (mucosa-associated lymphoid tissue) lymphomas. Eight of the tumors were treated surgically and an open biopsy of the parotid gland tumor was performed in 1 case and open biopsy of a neck lymph node in 2 cases for the purpose of diagnosis. After the diagnosis, these cases were followed up with or without radiotherapy and chemotherapy. Follow-up ranged from 6 to 109 months. The 5-year-survival rate was 60%. The outcome for this group was found to be as good as that reported by others.

Adult↗

PubMed1996

[Usefulness of open lung biopsy for corrective surgery on incomplete atrioventricular septal defect associated with severe pulmonary hypertension and right to left shunting].

In congenital heart defects, it is sometimes difficult to decide the operative indication in patients, who has severe pulmonary hypertension (PH) and right to left shunting, from clinical symptoms and cardiac catheterization. We here report a case of incomplete atrioventricular septal defect. The patient is 9 months old with the Down's syndrome. The cardiac catheterization showed severe PH and right to left shunting. Preoperative mean pulmonary artery pressure was 75 mmHg, pulmonary systemic pressure to systemic pressure ratio (PP/PS) was 1.17, pulmonary systemic flow to systemic flow ratio (QP/QS) was 0.79, pulmonary systemic resistance to systemic resistance ratio (RP/RS) was 1.54 and pulmonary vascular resistance (PVR) was 9.6 woodunits.m2. These data suggested that the irreversible pulmonary vascular disease was present. However the PVR decreased from 9.6 to 3.6 woodunits.m2 after inspiration of 100% oxygen. We therefore performed open lung biopsy for further evaluation of the pulmonary vascular bed. The pathological findings obtained at lung biopsy indicated that there was no irreversible pulmonary vascular disease. This case was diagnosed suitable for a corrective surgery. Total repair was performed and the subsequent clinical course was satisfactory. We thus suggest that the open lung biopsy is useful to decide the surgical indication when it is difficult to determine an operative indication from hemodynamic measurement alone.

Biopsy↗

PubMed1996

Apoptosis during an early stage of nephrogenesis induces renal hypoplasia in bcl-2-deficient mice.

Renal development in bcl-2-deficient mice was monitored to examine the temporal and spatial function of this gene during nephrogenesis in vivo. Extensive apoptosis occurred during abnormal nephrogenesis in bcl-2-deficient mice. In embryos and newborn mice, the sequence of morphological events was monitored by morphology in conjunction with morphometry, and bcl-2 -/-, bcl-2 +/-, and bcl-2 +/+ mice were compared. In bcl-2 -/- mice, initial induction of nephrons was detected by embryonic day 13 (E-13) as normal. Then, apoptotic cells became five times more frequent at E-13 to E-16 with a significant reduction (1/5) in nephron number at E-17 to E-19 in bcl-2 -/- mice compared with bcl-2 +/+ mice. No morphological difference was evident between bcl-2 +/- mice and bcl-2 +/+ mice by morphometry. Apoptotic cells were found mainly among the mesenchyme and less frequently in tubuli. Little apoptosis among ureteric buds was noted. In bcl-2 -/- mice at E-17 to E-19, inactive branching and insufficient convolution of ureteric buds were accompanied by fulminant apoptosis in the mesenchyme. Neonatal bcl-2 -/- mice lacked the nephrogenic zone, exhibiting renal hypoplasia. Thus, bcl-2 seems to inhibit apoptosis in renal stem cells during the induction of nephrons in vivo.

Animals↗

PubMed1996

[Distributions of pyrimidine nucleoside phosphorylase (PyNPase) in tissues of benign and malignant mammary diseases--immunohistochemical observations].

Pyrimidine nucleoside phosphorylase (PyNPase) is considered to be important for producing antitumor function of 5'-DFUR or 5-FU inducing compounds, since this enzyme transforms 5'-DFUR into 5-FU and 5-FU into their activated forms. Additionally, PyNPase shows high activity in various malignant tumor tissues. In this investigation, the distributions of PyNPase were examined in the tissues of mastopathy, fibroadenoma, phyllodes tumor and mammary cancer using immunohistochemical procedures. The following results were obtained. In the tissues of mastopathy or fibroadenoma, immunoreactivity was generally very weak and only a few positive epithelial cells were observed. In the phyllodes tumor, immunoreactivity was also weak, but every epithelial cell showed positive immunoreactivity. On the contrary, apparent immunoreactivity was observed in the tissues of mammary cancer, and cancer cells revealed prominent immunoreactivity.

Breast↗

PubMed1996

[A predictive and prognostic study on two cases of transient hyperphosphatasemia of infancy].

We presented two cases with transient hyperphosphatasemia (TH) of infancy, whose serum alkaline phosphatase (EC 3.1.3.1, ALP) activity showed markedly increased and the atypical isoenzyme fractions were seen by electrophoresis. These isoenzymes migrated into normal bone ALP region (alpha 2-beta globulin fraction) and fast liver ALP region (fast alpha 2 globulin fraction). From various investigation such as, heat stability, inhibition test by amino acid, neuraminidase treatment and Triton X-100 treatment, former fraction seemed to derive from bone ALP and later fraction from liver ALP. From our study, increment of the activity of alpha 2-beta gl fraction was in advance one month before maximum ALP activity stage, and fast alpha 2 gl fraction followed increasing 3 weeks after that. On the other hand, decreasing of fast alpha 2 gl fraction showed a shorter delay than alpha 2-beta gl fraction. These results suggest that a differential exchange of sugar chain or an impaired clearance of the enzyme from circulation was possibly occurred. It seemed to be important to increase a study of such a predictive and prognostic change of ALP activity and isoenzyme fraction in TH cases.

Alkaline Phosphatase↗

PubMed1996

[Long-term surgical effects of trabeculotomy combined with sinusotomy].

We retrospectively analyzed long-term effects of trabeculotomy combined with sinusotomy. We reviewed 29 eyes with primary open angle glaucoma and 6 eyes with psuedexfoliation glaucoma. The preoperative intraocular pressure was equal to or over 21 mmHg. All cases had been subjected to initial trabeculotomy combined with sinusotomy. The had been followed up for at least 3 years after surgery. The mean age was 57.8 years and the mean follow-up period was 40.5 months. The preoperative intraocular pressure was 24.3 +/- 5.9 mmHg (Mean +/- standard deviation) and the postoperative intraocular pressure was 15.8 +/- 3.8 mmHg. There was statistically significant difference between preoperative and postoperative intraocular pressure. The Kaplan-Meier life table method indicated a success rate at 50 months after surgery of 0.63 +/- 0.15, as defined by intraocular pressure of 20 mmHg or lower, and of 0.35 +/- 0.08 as defined by intraocular pressure equal to or lower than 14 mmHg. The success rate of filtering blebs was 0.10 +/- 0.05 at 50 months. Eleven of 35 eyes (37%) were controlled at equal to or below 14 mmHg and 20 of 35 (67%) eyes were controlled at equal to or lower than 16 mmHg at final postoperative intraocular pressure. The surgical results of trabeculotomy combined with sinusotomy remain effective in controlling intraocular pressure levels for long periods.

Adult↗

PubMed1996

Construction of the plasmid PMEX8-HAK1 and random site-directed mutagenesis of human cytosolic adenylate kinase.

The pMEX8-hAK1 vector was devised from the pAK plasmid (Kim J. H. et al., 1989, Protein Engineering 5, 379-386), which could directly express human adenylate kinase proteins without recombination and its single strand DNA could be withdrawn with helper phage for random site-directed mutagenesis. The conserved key residues at Lys21, Lys27, and Thr39 were engineered to obtain mutants for kinetic analysis. Three mutants were obtained as K21P, K27R, and T39S, their specific activities were strikingly reduced compared to those of wild type adenylate kinase. This pMEX8-hAK1 will be a powerful tool for site-directed mutagenesis to detect the substrate-enzyme interaction for human adenylate kinase including various other enzymes.

Adenylate Kinase↗

PubMed1996

[Studies of allergen specific IgE antibodies with atopic dermatitis--evaluation of house dust 6 (house dust Japan) specific IgE antibody].

We examined the usefulness of allergen housedust-6 measurement in 44 patients (22 males and 22 females) with atopic dermatitis. The positivity for each of housedust HD-2 and HD-6 and that for each of D-1 and D-2 was well correlated in more than 90% of the patients (correlation coefficient > 0.85). The positivity for HD-2 and for HD-6 was also correlated in 93.2% of the patients. However, there was a discrepancy between D-1 or D-2 and HD-2 or HD-6 in only a few patients. The positivity for antibody against specific IgE was higher in atopic dermatitis-patients with allergic rhinitis, allergic conjunctivitis or bronchial asthma as compared with patients with only atopic dermatitis. Only one patient with severe atopic dermatitis had a negative result for specific IgE, suggesting the contribution of other circumferencial factors in the development of the disease. In conclusion, our study suggested that housedust-6 is useful in clinical evaluation of patients with atopic dermatitis.

Adolescent↗

PubMed1996

Characteristics of airway eosinophils.

Eosinophils are important participants and contributors to allergic inflammation in asthma. The mechanisms by which eosinophils migrate to the airway and are activated are not clear. Moreover, there is evidence that eosinophils from the airway are functionally distinct from those cells in circulation. In initial studies, we have found distinct differences in function, cell surface markers, calcium metabolism in response to activation, and survival in eosinophils from the airway. In an attempt to ascertain what factors regulate these phenotypic changes, we have evaluated the effect of cytokines and adhesion on eosinophil function.

Asthma↗

PubMed1996

[Non-specific elevation of anti-dsDNA antibody measured by Farr method found in a patient with liver cirrhosis].

In a patient with liver cirrhosis, an elevation of serum anti-dsDNA antibody titer (100-193.3 IU/ml) measured by Farr method was found. This anti-dsDNA antibody was not identified by Crithidia Luciliae method, and the analysis using ELISA method showed that the DNA-antibody is an anti-ssDNA antibody (IgG) and that it is reactive only with ssDNA by the suppression test using purified DNA with lambda phage. Based on this finding, the high titer of anti-dsDNA antibody found in this patient using Farr method was considered to be non-specific cross-reaction with ssDNA.

Antibodies, Antinuclear↗

PubMed1996

[Assessment of proliferative cell nuclear antigen expression and clinical prognosis in gastric malignant lymphoma].

Clinicopathological study was performed in 15 resected cases of gastric malignant lymphoma. The clinicopathological features were as follows. 1) In 6 of 15 cases, the tumor was located in the upper part of the stomach. 2) Lymph node metastasis was observed in 5 of 12 cases. 3) In 3 of 15 cases, multiple tumorous lesions were noted. We also studied the relationship between PCNA expression and clinical prognosis in 10 cases, specimens of which were well preserved, out of 15 cases. About 500 nuclei immunohistochemically stained by PCNA monoclonal antibody were counted, and results were expressed by positive cell ratio (PCNA labelling index LI%). In conclusion, 1) the positive cases of lymph node metastasis showed a tendency for PCNA LI to increase compared with the negative cases. 2) The recurrent cases showed a tendency for increased PCNA LI compared with the cases without recurrence. 3) Cases with more than 60% of PCNA LI tended to have a poor prognosis compared with those of less than 60%.

Adult↗

PubMed1996

Nephrogenesis and renovascular development in angiotensinogen-deficient mice.

Angiotensinogen-deficient mice provide a model to examine the roles of angiotensin II as a renal growth factor in vivo. We monitored nephrogenesis and renovascular development in angiotensinogen-deficient mice from Embryonic Day 13 (E13) to 4 weeks after birth. Northern analysis of homozygote (Atg-/-) mice confirmed the absence of angiotensinogen mRNA in the liver and the kidneys. Embryonic kidneys in Atg-/- mice from E13 to E18 exhibited active nephrogenesis, as also observed in Atg+/- mice and Atg+/+ mice. Furthermore, metanephroi harvested at E12 from Atg-/- embryos showed branching morphogenesis of ureteric bud and tubulogenesis similar to metanephrol from Atg-/- embryos grown with exogenous angiotensin II in serum-free culture. In newborn Atg-/- mice, we observed uniform dilation of the pelvis accompanied by a coarse medulla, which was not noted in Atg+/- or Atg+/+ mice. Hydronephrosis in Atg-/- mice continued, and renal papillae underwent atrophy for the 4 weeks after birth. Another characteristic aspect of the morphology of Atg-/- mice was the thickening of vascular walls as little as 2 weeks after birth. Immunohistochemistry revealed recruitment of renin in hyperplastic vascular smooth muscle cells (VSMC) in Atg-/- mice after 2 weeks. Electron microscopy confirmed that the majority of hyperplastic VSMC contained various sized renin granules with abundant endoplasmic reticulum. In situ hybridization demonstrated that expression of renin mRNA became prominent in parallel with hyperplasia of VSMC, as well as recruitment of renin protein. Furthermore, at 4 weeks, Atg-/- mice expressed alpha-smooth muscle actin in the mesangium, whereas none was ever found in that of Atg+/- mice and Atg+/+ mice. In conclusion, the renin-angiotensin system seems not be essential for nephrogenesis in vivo. Furthermore, hyperplasia of VSMC and expression of the smooth-muscle phenotype in the mesangium are inducible even in the absence of angiotensin II, with hypotension, in vivo.

Angiotensinogen↗

PubMed1996

[Intraocular pressure decrease after phacoemulsification-aspiration+ intraocular lens implantation in primary open angle glaucoma eyes].

Phacoemulsification-aspiration and intraocular lens implantation (PEA + IOL) were carried out in 40 primary open angle glaucoma (POAG) eyes without history of surgery and 53 control (cataract only) eyes. Postoperative change in intraocular pressure (IOP) was evaluated over a long period (at least 18 months, average follow-up period 34 months). The postoperative IOP was significantly lower than the preoperative level in every group from 6 months to 3 years. An IOP decrease of 1.5 mmHg was maintained for 3 years in the control group. A decrease of 2.5 mmHg was stable for 3 years in the good POAG group in which preoperative IOP was controlled (< or = 20 mmHg) with medication. IOP decrease in the poor POAG group in which preoperative IOP was over 21 mmHg with medication, was 5.5 mmHg, and was maintained for 3 years. Medication did not differ significantly before or after the operation. These results imply that in POAG an IOP decrease can be expected after PEA + IOL.

Aged↗