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Biomedical subjects

M Maeda

Publications and source records attributed to M Maeda.

At least 577 records · Page 32Linked to original sources
PubMed1995

The influence of ageing on cisplatin pharmacokinetics in lung cancer patients with normal organ function.

This study was performed to identify any relationship between age and cisplatin (CDDP) pharmacokinetics in lung cancer patients. CDDP was given at a dose of 80 mg/m2 by 1-h intravenous infusion to 23 lung cancer patients. All patients had normal renal, hepatic, and bone marrow functions. We measured ultrafilterable platinum (U-Pt) and total plasma platinum (T-Pt) using atomic absorption spectrometry. There was significant correlation between the age of the patients and U-Pt pharmacokinetic parameters such as the area under the plasma concentration versus time curve (AUC), total clearance (Cl), and peak plasma concentration (Cmax) as well as the AUC of T-Pt (P < 0.05). We performed univariate regression analysis to examine the influence of factors aside from age on the AUC of U-Pt and T-Pt. Creatinine and GPT levels were significantly related to the AUC of U-Pt, and creatinine clearance and creatinine concentrations were significantly related to the AUC of T-Pt. Therefore, stepwise multiple-regression models for the AUC of U-Pt and T-Pt were developed to assess an age effect. Age was consistently an independent and significant predictor of the AUC of U-Pt and T-Pt.

Adult↗
PubMed1995

Cardiac dystrophin abnormalities in Becker muscular dystrophy assessed by endomyocardial biopsy.

Duchenne and Becker muscular dystrophy (DMD/BMD) are allelic variants caused by mutations in gene-encoding dystrophin. Abnormal expression of dystrophin in skeletal muscle has been shown to correlate with severity of disease. However, in BMD the severity of skeletal and cardiac involvement are not well correlated. We studied the immunostaining pattern of cardiac dystrophin in endomyocardial biopsy specimens from 83 patients with heart disease. Immunohistochemical assessment of dystrophin in four patients with BMD and cardiomyopathy showed a variable distributions of myocytes with continuous, discontinuous, or absent membrane immunostaining patterns. These patterns were obviously different from patterns of other heart diseases. We conclude that the discontinuous immunostaining pattern of cardiac dystrophin is characteristic of BMD and that an absent pattern may be associated with more severe cardiac dysfunction. Because genetic analysis cannot determine the correct diagnosis in 35% of DMD/BMD cases, we recommend routine examination of immunostaining patterns of dystrophin in endomyocardial biopsy specimens in patients with cardiomyopathy suspected to be the result of BMD.

Adult↗
PubMed1995

Effects of 17 beta-oestradiol and 5 alpha-dihydrotestosterone on the expression of the muscle and heart types of lactate dehydrogenase isozymes in the masseter muscle of developing mice.

17 beta-oestradiol (E2) and/or 5 alpha-dihydrotestosterone (5 alpha-DHT) had no effect on the expression of isozymes of lactate dehydrogenase (LDH) in the masseter muscle of intact male mice. However, treatment with E2 restored the level of the muscle (M) type of LDH isozyme, which had been reduced by testectomy, to that found in intact male mice treated with vehicle only. Moreover, 5 alpha-DHT alone was more effective than E2 in increasing the relative level of this isozyme in testectomized mice. 5 alpha-DHT had a more significant effect on the increase in the relative level of the M-type LDH isozyme when combined with E2. These results suggest that androgens promote, in the presence of oestrogens, the postnatal changes in the characteristics of the masseter muscle of developing male animals.

Animals↗
PubMed1995

In situ degradation and absorption of [15N]urea in chicken ceca.

[15N]Urea was introduced (in situ) into a ligated cecal pouch of chickens to determine if it is degraded therein and absorbed into the blood as ammonia during the following 60 min. A mean of 49% of the introduced urea-15N was recovered from the blood of the mesenteric vein draining the cecal pouch and 26% was recovered from the cecal lumen fluid. Of the urea-15N introduced into the pouch, 4%, 2%, 15% and 5% were detected as urea, ammonia and non-protein fractions, except urea and ammonia, and proteins in the lumen fluid, respectively. Non-protein-15N, except urea and ammonia, protein-15N, urea-15N and ammonia-15N values recovered in the cecal venous blood were 10%, 19%, 18% and 2% of the introduced 15N, respectively. Urea concentration in the cecal venous blood increased from 0.71 mg to 3.13 mg per 100 ml for the first 15 min after introduction of urea-15N (P < 0.01) then decreased until 60 min. No significant change was found in blood ammonia concentration, however, despite a small increase during the period 15-45 min after urea-15N introduction. Ammonia-15N increased in the caecal venous blood for the first 30 min then decreased to a plateau level of 43% of the peak level. The rates of increase of urea-15N and non-protein-15N concentrations attained maxima in the blood as early as 15 min, then decreased linearly (P < 0.05). It is concluded that, although urea is actively degraded to ammonia in the ceca, it is mostly absorbed from the ceca, not in the form of ammonia, but as protein, urea and amino acids.

Absorption↗
PubMed1995

Histopathological and capillaroscopical features of the cuticles and bleeding clots in ring or middle fingers of systemic scleroderma patients.

Sixty-three patients with systemic scleroderma (SSc) (Barnett I, 41; Barnett II, 17; Barnett III, 5), 14 with systemic lupus erythematosus (SLE), 9 with dermatomyositis (DM) and 10 healthy controls (HC) were subjected to histopathological examinations of the cuticles of ring or middle fingers. The sex ratios (male/female) in the patients with SSc, SLE, DM and HC were 7:56, 5:9, 5:4 and 5:5, and the ages were 22-74, 19-78, 45-70 and 13-78 years old, respectively. Biopsy samples were taken from the central portion of the cuticles, which showed the most severe change of elongation with or without bleeding clots of cuticle-proximal nailfolds (BC). Histopathologically, 61 (96.8%) cuticles of SSc patients consisted of the upper (U), middle (M) and lower (L) layers, which represent obliquely stacked, parabolic, and parallel stacked layers, respectively. The middle parabolic layer appeared to discharge homogenous eosinophilic globular deposits (ED). On the other hand, this typical three-layer-nail pattern was seen only in 9 (64.3%) of SLE, 3 (33.3%) of DM and none of HC, in total 12 (36.4%) of the non-SSc group, which included SLE, DM and HC. In SSc, there were statistical correlations (R2) between ED and BC, ED and cuticle-elongation, cuticle-layer and cuticle-elongation, ED and cuticle-layer, BC and cuticle-elongation. Capillaroscopically, bleeding clots located in the middle layer with ED of the cuticles in eight patients with SSc were transported rapidly within 1-2 weeks.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1995

Radiosynthesis, rodent biodistribution, and metabolism of 1-deoxy-1-[18F]fluoro-D-fructose.

Fluorine-18 labeled analog of D-fructose, 1-deoxy-1-[18F]fluoro-D- fructose (1-[18F]FDFrc), was synthesized by nucleophilic substitution of [18F]fluoride ion and the effect of the fluorine substitution on its in vivo metabolism was investigated. The tissue distributions of 1-[18F]FDFrc in rats and tumor bearing mice showed initial high uptake and subsequent rapid washout of the radioactivity in the principal sites of D-fructose metabolism (kidneys, liver and small intestine). The uptakes in the brain and tumor (fibrosarcoma) were the lowest and moderate, respectively, but tended to increase with time. The in vivo metabolic studies of 1-[18F]FDFrc and nonradioactive 1-FDFrc in mouse brain and tumor showed that the fluorinated analog remained unmetabolized in these tissues, indicating that the substitution of fluorine at the C-1 position produces a nonmetabolizable analog of D-fructose. Thus, 1-[18F]FDFrc had no features of a metabolic trapping tracer without showing any appreciable organ or tumor specific localization.

Animals↗
PubMed1995

Effect of colostomy on the occurrence of dietary [15N]urea in intestinal contents, blood, urine and tissues in chickens fed a low protein diet plus urea.

1. The occurrence of 15N was examined in excreta for 10 h, and in intestinal contents, blood and tissues at 10 h after [15N]urea was fed to conventional and colostomised cockerels. 2. Total-15N excretion and 15N-balance in control chickens were 18.88 and 44.79 mg/kg body weight/10 h), respectively. The former was increased and the latter was decreased by colostomy by 10.75 mg (P < 0.01). 3. Amounts of [15N]urea, [15N]ammonia and [15N]uric acid excreted by control birds were 13.78, 3.90 and 0.18 mg/kg body weight/10 h or 0.73, 0.21 and 0.01 of the total-15N excreted respectively. 4. The [15N]urea, [15N]uric acid and total-15N excreted were all increased after colostomy but [15N]ammonia was decreased (uric acid P < 0.05, others P < 0.01). The increase in total-15N was mostly accounted for by [15N]urea. 5. Colostomy resulted in significantly less total-15N in the contents of the whole intestine (P < 0.01), less total-15N, [15N]ammonia and [15N]urea in the contents of the colo-rectum (P < 0.01) and less total-15N and [15N]urea in the contents of the upper intestine (P < 0.05); it did not affect any in caecal contents. 6. [15N]Urea in blood, liver and kidney (blood P < 0.01, others P < 0.05), and [15N]glutamine amide (P < 0.05) and [15N]uric acid (P < 0.01) in blood were significantly decreased after colostomy. 7. The results support the hypothesis that most of the dietary urea is utilised as the result of a back-flow of ureteral urea into the caeca where it is rapidly converted into ammonia which is then metabolised to other compounds.

Animal Feed↗
PubMed1995

A MAP kinase necessary for receptor-mediated activation of adenylyl cyclase in Dictyostelium.

Analysis of a developmental mutant in Dictyostelium discoideum which is unable to initiate morphogenesis has shown that a protein kinase of the MAP kinase/ERK family affects relay of the cAMP chemotactic signal and cell differentiation. Strains in which the locus encoding ERK2 is disrupted respond to a pulse of cAMP by synthesizing cGMP normally but show little synthesis of cAMP. Since mutant cells lacking ERK2 contain normal levels of both the cytosolic regulator of adenylyl cyclase (CRAC) and manganese-activatable adenylyl cyclase, it appears that this kinase is important for receptor-mediated activation of adenylyl cyclase.

Adenylyl Cyclases↗
PubMed1995

A mouse monoclonal antibody, S2n8, detects a 140 kDa protein on the surface of human endometrial stromal cells and decidual cells.

We developed a mouse monoclonal antibody, S2n8, by immunizing mice i.p. with human decidual cells collected in the first trimester of pregnancy. By indirect immunofluorescence staining of frozen sections, S2n8 was found to react with decidual cells and endometrial stromal cells throughout the menstrual cycle, but not with endometrial glandular cells or with the endometrial surface epithelium. Judging from the fluorescence intensity, the antigen expression on stromal cells was weak in the proliferative phase, and became stronger in the secretory phase. Decidual cells in the first trimester of pregnancy and decidual cells at term showed strong expression of this antigen. Indirect immunofluorescence staining of enzymatically dispersed decidual tissue revealed that the S2n8 antigen was expressed on the decidual cell surface. Flow cytometric analysis of 12 freshly prepared stromal cell-enriched cell suspensions showed that 74.8-94.2% (mean +/- SD 86.1 +/- 6.6%) of the cells carried the antigen. The expression of S2n8 antigen on cultured stromal cells was enhanced by the addition of oestradiol and/or progesterone. The antigenic molecule was purified by immunoaffinity chromatography from decidua collected in the first trimester of pregnancy, and the molecular weight was estimated to be approximately 140 kDa. These findings indicate that the S2n8 antigen is a useful cell surface marker for stromal cells/decidual cells and is associated with their differentiation.

Animals↗
PubMed1995

Functional consequences of substitution of the disulfide-bonded segment, Cys127-Cys150, located in the extracellular domain of the Na,K-ATPase beta subunit: Arg148 is essential for the functional expression of Na,K-ATPase.

The Cys127-Cys150 disulfide-bonded loop (L1) of the Torpedo californica Na,K-ATPase beta 1 subunit was substituted with the corresponding loop of the rat beta 1, mouse beta 2, or pig H,K-ATPase beta subunit. All the substituted mutant beta subunits assembled with the Na,K-ATPase alpha subunit in a trypsin-resistant manner. The mutants with L1 from the Na,K-ATPase beta subunit isoforms (rat beta 1 and mouse beta 2) each formed a functional complex with the Na,K-ATPase alpha subunit. On the other hand, the complex of the alpha subunit with the mutant beta subunit that was substituted with the pig H,K-ATPase beta subunit L1 was inactive as to ATP hydrolysis. Ser131 and Phe148 located within L1 of the pig H,K-ATPase beta subunit-substituted mutant were back-mutated to Pro131 and Arg148, respectively. The Phe148 to Arg mutation restored the ability of the mutant beta subunit substituted with the H,K-ATPase beta subunit L1 to form a functional complex with the alpha subunit. These results suggested that the Cys127-Cys150 loop of the Na,K-ATPase beta 1 subunit, especially Arg148, plays a critical role in the functional expression of Na,K-ATPase.

Amino Acid Sequence↗
PubMed1995

The rat intrinsic factor gene: its 5'-upstream region and chief cell-specific transcription.

A DNA segment containing the 5'-upstream region and amino terminal reading frame of the gastric intrinsic factor gene was cloned from rat and its nucleotide sequence was determined. S1 mapping demonstrated that the transcription initiation site is located downstream of the second TATA-box sequence. Similar sequence motifs to those in the pepsinogen genes transcribed in gastric chief cells were found in the deduced sequence, suggesting that the rat intrinsic factor gene is transcribed in these cells. The genes for the intrinsic factor and its homologous protein transcobalamin I were apparently derived from a common ancestoral gene, since the positions of their intron insertions as well as the amino acid residues are conserved. Northern blot hybridization showed that the gene for the intrinsic factor is transcribed in the stomach but not detectably in the intestine, kidney, testis, brain, heart, liver, lung, or spleen. In situ hybridization using radioactive complementary RNA clearly indicated that the major transcription site in gastric glands is chief cells. Different locations of expression of intrinsic factor proteins in various mammals were observed previously using antibodies: in rat parietal cells and chief cells, in mouse chief cells, and in human parietal cells. The present results clearly demonstrated the intrinsic factor mRNA mainly in chief cells of adult rats, as in mice, suggesting that transcriptional regulation of the intrinsic factor gene is essentially the same in rodents.

Animals↗
PubMed1995

A porcine homolog of human integrin alpha 6 is a differentiation antigen of granulosa cells.

To search for new molecules relating to the mechanism(s) of follicular differentiation, we raised a new monoclonal antibody (mAb), POG-2, which reacted with the surface of porcine ovarian granulosa cells. An immunohistological study revealed that the antigen appeared initially on the primary follicles. The antigen expression increased during follicular development, reached the highest level in small follicles 1-2 mm in diameter, and then decreased in the preovulatory follicles. The antigen was not detected on luteal cells in the CL. SDS-PAGE profiles of POG-2 antigen purified from isolated porcine granulosa cells by immunoaffinity chromatography indicated that it consisted of two proteins (120 and 130 kDa) and that the antigenic epitope of POG-2 was on the 120-kDa protein. We next purified a large amount of POG-2 antigen from the homogenate of porcine ovaries by immunoaffinity chromatography. Analysis of the partial amino acid sequence of the 120-kDa protein showed that 16 amino acids from the amino terminus were very similar to those of both human and murine mature integrin alpha 6, with 88% homology. SDS-PAGE profiles revealed that the 120-kDa protein was bound to a 28-30-kDa protein by a disulfide bond; this was compatible with the reported characteristics of human integrin alpha 6. We then examined the immunoreactive distribution of integrin alpha 6 using anti-integrin alpha 6 mAb GoH3. The staining profiles obtained with GoH3 were very similar to those obtained with POG-2. These findings showed that the molecule detected by POG-2 was a porcine homolog of human integrin alpha 6 and that integrin alpha 6 was a differentiation antigen of porcine granulosa cells, suggesting an involvement of integrins in follicular differentiation.

Amino Acid Sequence↗
PubMed1995

Pharmacologic treatment of intimal hyperplasia after metallic stent placement in the peripheral arteries. An experimental study.

RATIONALE AND OBJECTIVES: To evaluate the efficacy of oral administration of cilostazol, an antithrombotic agent, for the prevention of thrombotic occlusion and intimal hyperplasia after stenting. METHODS: Single-bodied Z-stents were placed in the iliac arteries of 23 dogs. Before stenting, an embolizing coil was introduced into the right femoral artery to reduce blood flow in the right iliac artery. Eleven dogs were given cilostazol orally, and the other 12 were unmedicated as a control group. The dogs were killed at 4, 13, and 24 weeks. RESULTS: Intraluminal narrowing due to thrombus was observed in 25% of dogs in the control group but in none of the dogs in the cilostazol group. The thickness of the neointima was significantly thinner in the cilostazol group than in the control group at 24 weeks on the noncoiled side (P < 0.05), and at 4 and 24 weeks on the coiled side (P < 0.01). CONCLUSIONS: These results suggest that oral administration of cilostazol is an effective method of preventing thrombotic occlusion and intimal hyperplasia after stenting.

Administration, Oral↗
PubMed1995

Quantitative analysis and immunohistochemical studies on small intestinal mucosa of food-sensitive enteropathy.

Quantitative analysis and immunohistochemical studies of small intestinal mucosa were performed to investigate the mechanism of mucosal damage in 10 patients with food-sensitive enteropathy. Jejunal biopsy specimens were taken before and after treatment and after clinical relapse following a challenge test. The low villous height of untreated patients normalized after introduction of an elimination diet but declined again to subnormal level after a challenge test. Several other types of cells were significantly increased in the untreated patients in comparison to controls. These included HLA-DR+ (DR+) CD4+ cells in the lamina propria and intraepithelial CD8+ cells. Moreover, those cell patterns, such as increased DR+ CD4+ cells and CD8+ cells, normalized with treatment but regressed to pretreatment levels when the patients were challenged. These findings suggest that activated CD4+ cells in the lamina propria of the small intestinal mucosa, probably by releasing cytokines, may play an important role in contributing to mucosal damage in patients with food-sensitive enteropathy.

Animals↗
PubMed1995

Effects of pyridoxalated hemoglobin polyoxyethylene conjugate and other hemoglobin-related substances on arterial blood pressure in anesthetized and conscious rats.

The effects of pyridoxalated hemoglobin polyoxyethylene conjugate (PHP) and other hemoglobin-related substances on arterial blood pressure (ABP) and heart rate (HR) were examined. Infusion of PHP and other hemoglobin-related substances elevated ABP and increased HR. The degree of the increase in ABP and HR did not differ among the groups. There were species' differences in responses to PHP. Pretreatment with various blockers did not abolish the elevation of ABP. The pretreatment of NG-monomethyl-L-arginine dose-dependently reduced the elevation of ABP but did not completely abolish it. PHP also elevated ABP in conscious rats. The magnitude of the ABP elevation was significantly smaller than in the anesthetized rats. Results indicate that inhibition of nitric oxide (NO) might be responsible in part for the elevation of ABP, and the degree of the elevation would be dependent on the degree of contribution of NO to the regulation of ABP.

Adrenergic Antagonists↗
PubMed1995

Sympathetic reinnervation of unilaterally denervated rat lung.

The effect of unilateral sympathetic denervation and reinnervation of the lung on a variety of circulatory parameters was investigated in urethane-anaesthetized rats. The left main stem bronchus together with its surrounding nerves was cut and reanastomosed in 40 rats: 12 intact rats served as controls. Final experiments were performed after 0 days to 10 months: the left stellate ganglion was stimulated. The effect was greatest at 20 Hz. Pulmonary arterial pressure increased significantly (P < 0.05) by 10% and pulmonary flow decreased significantly (P < 0.05) by 16% in the control rats; no effect on these parameters was found in acutely denervated rats. The stimulus-elicited change in pulmonary arterial pressure reappeared 1 week after unilateral hilar stripping and gradually returned during reinnervation. After 10 months, the increase in pressure was significantly (P < 0.05) larger than that of the control by 50%, whereas the noradrenaline content of the reinnervated lung was significantly (P < 0.05) smaller than that of the intact side by 48%. This discrepancy may reflect denervation hypersensitivity of vascular muscle cells. The operations had no effect on systemic circulation: heart rate and systemic arterial pressure increased and aortic blood flow decreased to the same extent in all experimental groups during nerve stimulation. These results suggest that sympathetic reinnervation of the rat lung starts within 1 week but that reinnervation is still incomplete 10 months after unilateral hilar stripping.

Adrenergic Fibers↗