Biomedical subjects

M Mochizuki

Publications and source records attributed to M Mochizuki.

At least 73 records · Page 4Linked to original sources

PubMed2000

Differentiation induction of canine osteosarcoma cell lines by retinoids.

The effect of two retinoids, all- trans and 9- cis retinoic acid, on the differentiation of three canine osteosarcoma cells (OOS, HOS, and POS) was examined using markers specifically expressed by phenotypic osteoblasts. Both retinoids induced morphologic differentiation in all the canine osteosarcoma cells. Retinoids enhanced cell flattening and spreading, as well as reduction in cell overlapping. Alkaline phosphatase (ALP) activity and ALP staining was enhanced in OOS, and HOS cells, but decreased in POS cells. These results may suggest that OOS and HOS cells have immature osteoblastic properties and POS cells have mature osteoblastic properties. Retinoids decreased osteocalcin production in all the osteosarcoma cells. They induced an increase in production of type I collagen in HOS and POS cells, but a decrease in OOS cells. These results indicate that retinoids induce differentiation of canine osteosarcoma cells, resulting in an altered expression of their malignant phenotype.

Alitretinoin↗

PubMed2000

Clinical features of human T-lymphotropic virus type 1 uveitis: a long-term follow-up.

To investigate the clinical manifestations of human T-lymphotropic virus type-1 uveitis (HU), 112 HU patients who were followed up periodically for more than one year were retrospectively analyzed with respect to their ophthalmological and systemic complications. The gender ratio (female/male ratio) of the HU patients was 2.0 and the initial complications were foggy vision in 34.5%, ocular floaters in 33.3%, and blurred vision in 15.5%. As for the ocular symptoms, the majority (78.6%) of patients were classified as intermediate uveitis with vitreous inflammation. Recurrence of uveitis episodes was seen in one half of the patients (51.8%); 12 patients had more than six uveitis episodes. The interval of uveitis episodes varied from two weeks to 10 years. Nearly one half of the patients (43.8%) had ocular complications: e.g., cataract in 22 patients, persistent vitreous opacities in 17 patients, and glaucoma in 16 patients. Although the visual prognosis was essentially good, 11 patients had poor visual prognosis (<0.1). The causes of poor vision in these patients were cataract, cystoid macular edema, epiretinal membrane, and optic nerve atrophy. Of the 112 HU patients, two developed HTLV-I-associated myelopathy (TSP/HAM) after the onset of HU, while none developed adult T-cell leukemia. Sixteen HU patients had a previous history of Graves' disease and a past history of methimazole therapy, while Graves' disease was found in another HU patient only after HU onset and methimazole was not administered before the onset of HU. The present data of long-term follow-up indicate that (1) HU causes various ocular complications and its visual prognosis can be poor, (2) TSP/HAM can be induced even after the onset of HU, and (3) methimazole is not a risk factor of HU after Graves' disease.

Adult↗

PubMed2000

Immunoregulation by aqueous humor.

PURPOSE: The eye is a classic example of an immune-privileged site. To investigate the local defense system of the eye, the immunosuppressive effects of the aqueous humor on cytokine production was examined. METHODS: Using T cell clones (TCCs) established from infiltrating cells in the aqueous humor of patients with human T lymphotropic virus type 1 (HTLV-1) uveitis as target cells and the aqueous humor of patients with senile cataract obtained during cataract surgery, we examined the effects of the aqueous humor on the production of cytokines by HTLV-1-infected TCCs. RESULTS: HTLV-1-infected TCCs produced large amounts of various cytokines. The aqueous humor inhibited the production of cytokines in a dose-dependent manner. The inhibitory activity was heat labile. First protein liquid chromatography showed at least four major peaks of different molecular size, indicating that the aqueous humor contains multiple immunosuppressive factors. Transforming growth factor-beta, alpha-melanocyte-stimulating hormone, and vasoactive intestinal peptide did not suppress cytokine production. The inhibitory activity was neutralized by monoclonal antibody to Fas ligand. CONCLUSION: These data suggest that soluble Fas ligand is a candidate suppressive factor in the aqueous humor.

Aqueous Humor↗

PubMed2000

Expression and processing of the canine calicivirus capsid precursor.

The ORF2 product of canine calicivirus (CaCV) was identified and its processing in mammalian cells was analysed. Immunoblot analysis revealed the presence of the 75 kDa capsid precursor in addition to a 57 kDa capsid protein and a 22 kDa N-terminal polypeptide in CaCV-infected cells treated at an elevated temperature. When the CaCV ORF2 was expressed in a transient mammalian expression system, only the 75 kDa precursor was detected in immunoblot analysis, suggesting that no post-translational processing occurred in this system. However, the precursor was processed to a 57 kDa protein and a 22 kDa polypeptide by the proteinase of feline calicivirus (FCV) when this was co-expressed with ORF2. Processing was blocked by site-directed mutagenesis of the putative cleavage site in the capsid precursor. The results indicate that the proteinase of FCV can cleave the capsid precursor of CaCV to produce the mature capsid protein and that CaCV may have a similar proteinase.

Animals↗

PubMed2000

Low susceptibility of Long-Evans Cinnamon rats to N-butyl-N-(4-hydroxybutyl)-nitrosamine-induced urinary bladder carcinogenesis and inhibitory effect of urinary copper.

We studied the susceptibilities to N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN)-induced urinary bladder carcinogenesis of male Long-Evans Cinnamon (LEC), F344 and Long-Evans Agouti (LEA) rats. Male rats (n=21) were given 0.1% BBN in their drinking water from week 6, 8 and 10 for one week, and killed in week 56. The incidences of transitional cell tumors (papillomas plus carcinomas) in BBN-treated LEC and F344 rats were 12% and 76%, respectively (P<0.001, experiment 1), and those in LEC and LEA rats were 11% and 95%, respectively (P<0.001, experiment 2). When male LEC and F344 rats were given 0.1% BBN in their drinking water for 7 days, the intake of BBN and the urinary concentration of its active metabolite, N-butyl-N-(3-carboxypropyl)nitrosamine (BCPN), were higher in the LEC rats (P<0.01). The urinary pHs of untreated LEC and F344 rats were similar between week 6 and 30. The urinary copper concentration was lower in LEC rats before jaundice than in F344 rats, but its concentrations in 28- and 50-week-old LEC rats were 1.7 and 2.3 times those in F344 rats. In a two-stage carcinogenesis study using F344 rats, i.p. injections of cupric nitrilotriacetate increased urinary copper excretion, and inhibited BBN-induced bladder carcinogenesis. In a two-stage carcinogenesis study using LEC rats, oral administration of D-penicillamine decreased urinary copper excretion, and increased BBN-induced bladder cancer, although the difference was not significant. These data show that LEC rats are resistant to bladder carcinogenesis and suggest that urinary copper has a significant role in their resistance.

Age Factors↗

PubMed2000

Soluble Fas ligand and soluble Fas in ocular fluid of patients with uveitis.

AIMS: To investigate the presence of soluble Fas ligand (sFasL) and soluble Fas (sFas) in ocular fluid of patients with uveitis. METHODS: Samples of aqueous humour (AH, n=17), vitreous fluid (n=9), and serum (n=60) were collected from patients with uveitis which included Behçet's disease, Vogt-Koyanagi-Harada disease, sarcoidosis, human T lymphotropic virus type 1 (HTLV-I) uveitis, sympathetic ophthalmia, HLA-B27 associated acute anterior uveitis, and ocular toxoplasmosis. The AH of patients with age related cataract without uveitis obtained during cataract surgery was used as controls (n=20). The amounts of sFasL and sFas were measured by enzyme linked immunosorbent assay. RESULTS: Significant amounts of sFasL were detected in AH of patients with age related cataract (non-uveitis group). sFasL was also detected in AH of patients with uveitis, though the amounts were slightly lower than those in the non-uveitis group. On the other hand, the levels of sFas in AH of patients with uveitis were significantly higher than those in controls. As for the disease activity, the levels of sFasL and sFas in the vitreous fluid of patients with active uveitis were significantly higher than those in inactive uveitis. sFasL in the serum of healthy donors and patients with uveitis was below detectable levels, except for patients with HTLV-I uveitis who had significant amounts of sFasL in the serum. The levels of sFas in the serum of patients with Behçet's disease, sarcoidosis, and HTLV-I uveitis were significantly higher than those of healthy donors. CONCLUSIONS: sFasL is present in the AH of non-uveitic eyes with age related cataract. Intraocular levels of sFasL and sFas are significantly increased in uveitis, particularly in active uveitis. These data suggest that intraocular sFasL and sFas may have a regulatory role in uveitis.

Adult↗

PubMed2000

Effect of milrinone on left ventricular relaxation and Ca(2+) uptake function of cardiac sarcoplasmic reticulum.

Milrinone, a phosphodiesterase 3 (PDE3) inhibitor, is known to enhance left ventricular (LV) contractility by an inhibition of the breakdown of cAMP through the mechanism inhibiting PDE3. However, it is unclear whether milrinone also exerts positive lusitropy, like dobutamine. Here, we assessed the effects of milrinone on in vivo LV relaxation, as well as the Ca(2+)-ATPase activity and the Ca(2+) uptake function of the cardiac sarcoplasmic reticulum (SR), compared with the effect of dobutamine on those functions. After dobutamine (3 microg x kg(-1) x min(-1)) was administered, the peak value of the first derivative of LV pressure (+dP/dt) increased by 46%, whereas the time constant (tau) of LV pressure decay decreased by 6.9%, respectively. After milrinone (10 microg/kg) was administered, the peak +dP/dt increased to a similar extent as dobutamine (46%), whereas tau decreased much more than dobutamine (19.9%; P < 0.05). In LV crude homogenate, the thapsigargin-sensitive, Ca(2+)-ATPase activity-cAMP relationships was significantly less increased by milrinone compared with dobutamine (P < 0.05), indicating the higher sensitivity of the SR Ca(2+)-ATPase activity on cAMP by milrinone than by dobutamine. In the SR vesicles purified from LV muscles, the addition of cAMP increased the SR Ca(2+) uptake in a dose-dependent fashion, and the PDE3 inhibitors (milrinone and cGMP) significantly augmented this response (P < 0.05). Hence, milrinone substantially improved LV relaxation in association with an acceleration of the SR Ca(2+)-ATPase activity and the SR Ca(2+) uptake. This acceleration might be due to an inhibition of the membrane-bound PDE3 in the SR, leading to a local elevation of cAMP.

Adrenergic beta-Agonists↗

PubMed2000

Bilateral serous retinal detachment associated with Alport's syndrome.

We report a 14-year-old girl with Alport's syndrome who developed bilateral exudative retinal detachment in the macula. With the development of chronic renal failure, bilateral serous retinal detachment appeared which had the retinal flecks characteristic of Alport's syndrome. The serous detachment was resolved and vision recovered following intensive hemodialysis. As far as we know this is the first case with documentation of the onset and resolution of serous retinal detachment in Alport's syndrome.

Adolescent↗

PubMed2000

Synthesis and properties of novel bifunctional nitrosamines with omega-chloroalkyl groups.

Novel N-nitroso-N-(acetoxymethyl)-omega-chloroalkylamines were synthesized and their chemical and biological properties were evaluated. The nitrosamines were expected to decompose through omega-chloroalkyldiazohydroxides in aqueous solution, and then to alkylate various cellular macromolecules. N-Nitroso-N-(acetoxymethyl)-2-chloroethylamine rapidly decomposed in aqueous solution, and the reaction rate was apparently independent of the pH of the solution. On the other hand, the rate of decomposition of chloropropyl and chlorobutyl homologs was pH-dependent, and increased in alkaline solution. When mutagenicity was assayed in Salmonella typhimurium TA1535 and TA92 for preliminary evaluation, all three compounds were directly mutagenic. The mutagenicity in Salmonella typhimurium TA1535, which can detect base-pair change mutation, clearly showed that these compounds induced DNA alkylation in vivo. The increase of alkyl chain length in chloroalkyl compounds increased the mutagenic activity, and the activities were stronger than those of the corresponding simple alpha-acetoxy nitrosamines lacking a chloro group, N-nitroso-N-(acetoxymethyl)alkylamines. Furthermore, the positive result in TA92 suggested that chlorinated nitrosamines cross-linked DNA like antitumor chloroethylnitrosoureas and that they are expected to be new lead compounds for antitumor agents.

Alkylation↗

PubMed2000

[Activation of environmental carcinogenic N-nitrosodialkylamines by model systems for metabolic oxidation].

Nitrosamines are environmental carcinogens, and their relevance to human cancer is highly suspected. Dialkylnitrosamines require activation through metabolizing enzymes before they become ultimate electrophilic active species. This review summarizes two model systems for metabolic oxidation of dialkylnitrosamines. One system utilizes porphyrin and oxidant as a model for shunt pathway in the metabolizing pathway of cytochrome P450, and the other one utilizes Fenton reagent. Porphyrin and oxidant activated nitrosodialkylamines into direct acting mutagen by releasing aldehydes. During the process the alkylating activity was observed and alcohols are formed from the alkylation of water. Fenton reagent, consisting of iron salt and hydrogen peroxide supplemented with copper salt, activated dialkylnitrosamines into mutagens of a novel type containing an oxadiazine ring as their proposed structures. These works with model systems open a new aspect into the elucidation of the mechanism of xenobiotic metabolism.

Alkylation↗

PubMed2000

Retinoid receptors and the induction of apoptosis in canine osteosarcoma cells.

Retinoids, all-trans-retinoic acid (ATRA) and 9-cis-retinoic acid (9-cis-RA), induced morphological changes and apoptosis-like cell death characterized by cell shrinkage, chromatin condensation and nuclear disintegration in three canine osteosarcoma cells, OOS, HOS and POS, at a concentration of 10(-5) M. Both retinoid receptors, RARs and RXRs, were identified in these cells. 9-cis-RA bound to both the RXRs and the RARs, whereas ATRA bound to only the RARs in these cells. Those results indicate that the induction of apoptosis in canine osteosarcoma cells may be mediated by the specific control of RARs and RXRs.

Alitretinoin↗

PubMed2000

Recent epidemiological status of feline upper respiratory infections in Japan.

Epidemiology of upper respiratory infections of cats was studied. Nasal, ocular, and oral swabs collected from 111 cats presented at animal hospitals during the past 2.5 years were examined. Twenty-four (21.6%) and 4 (3.6%) cats were diagnosed as feline calicivirus (FCV) infection and feline viral rhinotracheitis, respectively, indicating FCV is more prevalent than feline herpesvirus-1, which revealed a considerable shift from data obtained in 1970s. Cat sera immunized by using vaccines containing either FCV F9 or 255 strains neutralized 42.9% and 66.7% of the FCV isolates, respectively. Chlamydia psittaci, examined by a PCR assay amplifying the ompA gene, was found in 26.9% of 26 diseased cats that typically showed conjunctivitis and rhinitis.

Animals↗

PubMed2000

Contrastive prevalence of feline retrovirus infections between northern and southern Vietnam.

The prevalence of infections with three feline retroviruses; feline leukemia virus (FeLV), feline immunodeficiency virus (FIV) and feline foamy virus (FeFV), was examined in domestic cats (Felis catus) and leopard cats (Felis bengalensis) in southern Vietnam in 1998. We then compared this data with our previous study in northern Vietnam in 1997. None of the cats had FeLV antigens in both the northern and southern areas. In contrast, there is a great distinction in the seropositivity of FIV. Twenty-two percent of domestic cats had FIV antibodies whereas no FIV positive cats were detected in northern area. FIV may have entered southern Vietnam recently and spread rapidly. FeFV infections were found in both areas, suggesting that FeFV might be present in the cat populations in Vietnam from the earliest time.

Animals↗

PubMed2000

A role of free insulin-like growth factor-I in dawn phenomenon in children and adolescents with type 1 diabetes mellitus.

It has been hypothesized that a decreased amount of the free form of insulin-like growth factor-I (fIGF-I) results in morning hyperglycemia in patients with type 1 diabetes mellitus. In this study, we attempted to clarify the role of fIGF-I in relation to total IGF-I (tIGF-I) and its related peptides or proteins in type 1 diabetes. Forty-seven patients with type 1 diabetes, mean age 13.7 years, were evaluated. Blood samples were obtained for the measurement of BG at 0200, 0400 and 0700, and of insulin, total IGF-I (tIGF-I), fIGF-I, IGFBP-1 and IGFBP-3 at 0700. The SD scores (SDS) were determined for the levels of tIGF-I, flGF-I, IGFBP-1 and IGFBP-3 by using Japanese reference data. The morning increase in BG (deltaBG(4-7)) correlated significantly with fIGF-I SDS (r=-0.352, p=0.0152) and IGFBP-1 SDS (r=0.438, p=0.0021), but did not correlate significantly with the fIGF-I level itself or the ratio of fIGF-I to tIGF-I (f/t IGF-I ratio). Hereupon, the f/t IGF-I ratio correlated positively with fIGF-I SDS (r=0.541, p=0.0003). The mean+/-SD in the f/t IGF-I ratio was 0.94+/-0.43%, and that in fIGF-I SDS was -0.50+/-1.32. The level of IGFBP-I SDS correlated negatively with fIGF-I SDS (r=-0.472, p=0.0008) and insulin (r=-0.365, p=0.0116). We suggest that the morning level of fIGF-I SDS, rather than the fIGF-I level itself, may be a useful marker of decreased insulin-like bioactivity in the dawn phenomenon in type 1 diabetes mellitus.

Adolescent↗

PubMed2000

Effect of all-trans and 9-cis retinoic acid on growth and metastasis of xenotransplanted canine osteosarcoma cells in athymic mice.

OBJECTIVE: To determine effects of all-trans and 9-cis retinoic acid (RA) on tumor growth and metastatic ability of canine osteosarcoma cells transplanted into athymic (nude) mice. ANIMALS: Forty-five 5-week-old female BALB/c nude mice. PROCEDURE: 1 X 10(7) POS osteosarcoma cells were transplanted subcutaneously into the intrascapular region of mice. All-trans RA (3 or 30 microg/kg of body weight in 0.1 ml of sesame oil), 9-cis RA (3 or 30 mg/kg in 0.1 ml of sesame oil), or sesame oil (0.1 ml; control treatment) were administered intragastrically 5 d/wk for 4 weeks beginning 3 days after transplantation (n = 4 mice/group) or after formation of a palpable tumor (5 mice/group). Tumor weight was estimated weekly by measuring tumor length and width, and retinoid toxic effects were evaluated daily. Two weeks after the final treatment, mice were euthanatized, and number of mice with pulmonary metastases was determined. RESULTS: Adverse treatment effects were not detected. Tumor weight was less in mice treated with either dose of 9-cis RA than in control mice, although this difference was not significant. Treatment with 30 mg of 9-cis RA/kg initiated after tumor formation significantly reduced the incidence of pulmonary metastasis, compared with the control group. CONCLUSIONS AND CLINICAL RELEVANCE: 9-cis RA decreased the incidence of pulmonary metastasis in nude mice transplanted with canine osteosarcoma cells and may be a potential adjunct therapy for treatment of osteosarcoma in dogs.

Alitretinoin↗

PubMed2000

In vitro retinoid-induced growth inhibition and morphologic differentiation of canine osteosarcoma cells.

OBJECTIVE: To determine differentiation and growth inhibition effects of retinoids on canine osteosarcoma cells. SAMPLE POPULATION: 3 osteosarcoma cell lines established from osteosarcomas in dogs. PROCEDURE: Osteosarcoma cells were incubated with various concentrations of all-trans-retinoic acid and 9-cis-retinoic acid or control medium, counted daily for 10 days, and evaluated for morphologic changes. Synthesis of DNA was measured by use of a cell proliferation ELISA. To analyze effect of retinoids on colony formation on plastic dishes, cells were cultured for 14 days, fixed, and stained; number of colonies was counted. RESULTS: In a dose-dependent manner, both retinoids induced morphologic differentiation and growth inhibition in the 3 osteosarcoma cell lines and inhibited each cell's ability to form anchorage-dependent colonies. CONCLUSION AND CLINICAL RELEVANCE: Retinoids induced differentiation of osteosarcoma cells of dogs, resulting in altered expression of their malignant phenotype. Induction of differentiation by retinoids may have potential as an adjunctive treatment for osteosarcoma in dogs.

Alitretinoin↗

PubMed2000

Serum itraconazole and hydroxyitraconazole concentrations and interaction with digoxin in a case of chronic hypertrophic pachymenigitis caused by Aspergillus flavus.

A patient treated with itraconazole (ITCZ) under the diagnosis of Aspergillus flavus-induced chronic hypertrophic pachymeningitis is presented. The reason for the successful cure of this patient was investigated by the pharmacokinetic analysis of serum levels of ITCZ. Concurrently administered digoxin was also investigated for its drug-drug interaction. The patient (a 75-year-old male) developed ophthalmopathy, and was diagnosed as having A. flavus hypertrophic pachymeningitis by pachymeninx biopsy. After admission, he was treated with FLCZ, AMPH, 5-FC and MCZ. The infection tended to subside with the AMPH administration. Since renal insufficiency was induced by AMPH and the other antifungal drugs were ineffective, daily administration of 200 mg of ITCZ was initiated, and the inflammatory signs and symptoms gradually subsided. The symptoms did not recur during the 36 months of itraconazole treatment after discharge, and it was concluded that ITCZ was effective for A. flavus hypertrophic pachymeningitis. Pharmacokinetic parameters of ITCZ and OH-ITCZ as follows: ITCZ: Cmax 93.2 ng/ml, T1/2 beta 11 hours, AUC0-24 999 ng.h/ml, OH-ITCZ: Cmax 159.4 ng/ml, T1/2 beta 16. 2 hours, AUC0-24 of 1391 ng.h/ml. Both ITCZ and OH-ITCZ reached steady states seven days after administration began. The ITCZ and OH-ITCZ levels in serum collected 36 months after the initiation of administration were 452.9 ng/ml and 1233.6 ng/ml, respectively. Cmax and AUC0-24 of ITCZ and OH-ITCZ on the second day were markedly lower than those in healthy adults reported by Oguchi et al., and hypoalbuminemia observed at administration on that day was considered the most probable cause. It was assumed that the most plausible reason for a successful cure even at a low dose of ITCZ was the increase of distribution to tissue by the increase of the unbound form. Digoxin was concurrently given to this patient at 0. 125 mg/day, but the blood digoxin level was not elevated. Consideration of the blood level of albumin is believed to be important for evaluating the blood concentration of ITCZ.

Aged↗

PubMed2000

Kinetics of apoptotic cells in experimental autoimmune uveoretinitis.

PURPOSE: To investigate the role of apoptosis in immunopathogenic mechanisms of experimental autoimmune uveoretinitis (EAU), the kinetics of apoptotic cells and expression of Fas and Fas ligand (FasL) in the eye with EAU were studied. METHODS: Male inbred Lewis rats were immunized with S-antigen (40 microg/rat), and eyes were examined to detect apoptotic cells on days 1, 4, 8, and 10 post-immunization and days 0, 2, 4, 6, and 8 after the onset of EAU. The clinical and pathologic scores were used for estimating EAU. Apoptotic cells were analyzed by TdT-mediated dUTP nick-end labeling, electron microscopic and immunohistologic examinations, and agarose gel electrophoresis. The anti-rat Fas and anti-rat FasL antibodies were used to examine the expression of Fas and FasL. RESULTS: Apoptotic cells were detected in the infiltrating cells in the aqueous humor, the vitreous body, the iris-ciliary body, and the retina. Apoptotic cells were observed as early as the day of EAU onset and reached a peak on day 2 after the disease onset. Fas and FasL were expressed on the infiltrating cells in the aqueous humor and the vitreous. FasL was expressed on resident cells of the ciliary body. The kinetics of the expression of FasL corresponded with the kinetics of apoptotic cells. CONCLUSIONS: Fas-FasL-mediated apoptosis is considered to occur in the eye with EAU and plays a role in the immunopathogenic mechanisms to eliminate ocular infiltrating cells, thereby down-regulating the inflammatory processes.

Animals↗