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Biomedical subjects

K Tsukiyama

Publications and source records attributed to K Tsukiyama.

At least 19 recordsLinked to original sources

Effects of an aldose reductase inhibitor on gastroenteropathy in streptozotocin-diabetic rats.

We investigated the effects of epalrestat, an aldose reductase inhibitor (ARI), on gastric emptying, fecal water content, and electrolyte transport in distal colon in streptozotocin (STZ)-induced diabetic rats. We measured gastric emptying time by acetaminophen method and short-circuit-current (Isc) in colonic mucosa using an Ussing chamber. The Isc in response to electric-field-stimulation (EFS) was decreased in untreated rats due to suppression by Cl- secretion. ARI treatment alleviated this suppression (2.7 +/- 0.6 vs. 7.4 +/- 1.1 microA/0.38 cm2 at 8 weeks after treatment, 1.1 +/- 0.2 vs. 7.0 +/- 1.0 at 12 weeks after treatment, P<0.05). In addition, the percentage of fecal water content in untreated rats was significantly lower than in ARI-treated rats (58.0 +/- 2.0 vs. 67.6 +/- 0.8% at 8 weeks, 56.9 +/- 2.1 vs. 63.4 +/- 1.4 at 12 weeks, P<0.05). From STZ injection to 8 weeks, the serum levels of acetaminophen in the diabetic rats were significantly lower than in controls, indicating delayed gastric emptying. At 12 weeks in the diabetic rats treated with ARI, the serum levels of acetaminophen were significantly higher than in the untreated diabetic rats (6.6 +/- 0.4 vs. 3.5 +/- 0.5 microg/ml, P<0.05). ARI-treatment ameliorated delayed gastric emptying without improving glycemic control. These findings show that ARI partially prevented progression of impaired gastric emptying, ion transport, and water transport, and suggest that epalrestat might be useful in the treatment of diabetic gastroenteropathy.

Acetaminophen↗

A novel glucokinase regulator in pancreatic beta cells: precursor of propionyl-CoA carboxylase beta subunit interacts with glucokinase and augments its activity.

A glucokinase regulatory protein has been reported to exist in the liver, which suppresses enzyme activity in a complex with fructose 6-phosphate, whereas no corresponding protein has been found in pancreatic beta cells. To search for such a protein in pancreatic beta cells, we screened for a cDNA library of the HIT-T15 cell line with the cDNA of glucokinase from rat islet by the yeast two hybrid system. We detected a cDNA encoding the precursor of propionyl-CoA carboxylase beta subunit (pbetaPCCase), and glutathione S-transferase pull-down assay illustrated that pbetaPCCase interacted with recombinant rat islet glucokinase and with glucokinase in rat liver and islet extracts. Functional analysis indicated that pbetaPCCase decreased the K(m) value of recombinant islet glucokinase for glucose by 18% and increased V(max) value by 23%. We concluded that pbetaPCCase might be a novel activator of glucokinase in pancreatic beta cells.

Animals↗

The E(2)Sigma(+) --> C(2)Pi Transition of NO and Term Values for the A, D, E, and C Lowest Rydberg Levels.

The E(2)Sigma(+) --> C(2)Pi Rydberg-Rydberg transition of (14)N(16)O near 8492 cm(-1) has been studied by Fourier transform spectrometry in the emission from a dc excited supersonic jet expansion and from a dc discharge under equilibrium conditions. The same transition has also been observed in laser-induced stimulated emission. Line wavenumbers of the 0-0, 1-1, and 2-2 bands, together with data for previously published near-infrared transitions, have been reduced to consistent sets of rovibronic term values for v = 0, 1, and 2 of the A(2)Sigma(+), D(2)Sigma(+), E(2)Sigma(+), and C(2)Pi states which frequently serve as intermediates in the multiphoton excitation of higher Rydberg levels of NO. Copyright 2000 Academic Press.

Journal Article↗

Overexpression of bcl-2 in transient abnormal myelopoiesis associated with Down syndrome.

Transient abnormal myelopoiesis (TAM) is a haematological complication found in Down syndrome. To determine the mechanisms of sustained proliferation of TAM cells, we studied the expression of apoptosis-related proteins, such as bcl-2, Fas (APO-1/CD95) and p-53, in peripheral blood cells from a new-born infant with Down syndrome and TAM. Using flow cytometry, peripheral blood mononuclear cells (PBMCs), consisting mostly of blast cells, showed marked expression of bcl-2 protein but not of Fas or p-53 products. DNA gel electrophoresis of PBMCs, cultured in the absence of serum factors, revealed no marked fragmentation. Our findings suggest that bcl-2 overexpression may be associated with prolonged cell survival of TAM cells.

Down Syndrome↗

Activating transcription factor-2 is a positive regulator in CaM kinase IV-induced human insulin gene expression.

Insulin plays a crucial role in the regulation of glucose-homeostasis, and its synthesis is regulated by several stimuli. The transcription of the human insulin gene, enhanced by an elevated intracellular concentration of calcium ions, was completely blocked by Ca2+/calmodulin-dependent protein kinase inhibitor. The activity of the transcription factor activating transcription factor-2 (ATF-2), which binds to the cAMP responsive elements of the human insulin gene, was enhanced by Ca2+/calmodulin-dependent protein kinase IV (CaMKIV). Mutagenesis studies showed that Thr69, Thr71, and Thr73 of ATF-2 are all required for activation by CaMKIV. CaMKIV-induced ATF-2 transcriptional activity was not altered by activation of cJun NH2-terminal protein kinase (JNK) or p38 mitogen-activated protein (MAP) kinase. Furthermore, when transfected into rat primary cultured islets, ATF-2 enhanced glucose-induced insulin promoter activity, whereas cAMP response element-binding protein (CREB) repressed it. These results suggest a mechanism in which ATF-2 regulates insulin gene expression in pancreatic beta-cells, with the transcriptional activity of ATF-2 being increased by an elevated concentration of calcium ions.

Activating Transcription Factor 2↗

The H1Sigma+ g (v = 0 and 1) and EF1Sigma+ g (v = 28 and 32) States of D2: Term Values and Fluorescence Lifetimes.

The extreme ultraviolet-visible double resonant excitation method was applied to the gerade Rydberg states of D2 molecules. Tunable coherent extreme ultraviolet radiation near 103 nm prepared D2 in the B1Sigma+ u (v = 7, J) state. Visible laser light subsequently brought them to the H1Sigma+ g (v = 0 and 1), EF1Sigma+ g (v = 28 and 32), and GK1Sigma+ g (v = 2 and 5) states. Our term values for the GK1Sigma+ g state were in complete agreement with previous values, while deviations beyond the experimental error were found for the H1Sigma+ g (v = 1) and EF1Sigma+ g (v = 28 and 32) states. The fluorescence lifetimes, measured under a collision-free environment for the first time, were in reasonable agreement with ab initio calculations. Copyright 1998 Academic Press.

Journal Article↗

Serum copper and ceruloplasmin activity at the early growing stage in foals.

Serum concentrations of copper (Cu), zinc (Zn), manganese (Mn), calcium (Ca) and inorganic phosphorus (P), as well as antigenic ceruloplasmin (Cp) and oxidase activity as a functional index for copper metabolism, were measured in 10 foals (5 males and 5 females) and their dams. Samples were harvested from the foals within 1 wk after birth and monthly from 1 to 17 mo of age. Samples were collected from their dams in the perinatal period (monthly from 2 mo before delivery to 5 mo postpartum). Serum oxidase activity, antigenic Cp and Cu in foals were extremely low at 1 wk. Serum Cp had the lowest value of 17.0 +/- 8.0 (mean +/- SD) mg/dL within the 1st wk, then increased rapidly up to 43.7 +/- 5.8 mg/dL at 1 mo, and maintained this level until the 17th mo. Serum Zn in foals had the highest value of 73.2 +/- 13.1 micrograms/dL within 1 wk, then decreased to 38.3 +/- 5.9 micrograms/dL by 17 mo. Serum Mn, Ca and P in mares were almost stable and within established reference ranges for our laboratory in the perinatal period, and these values in foals were also in the normal range. Even on appropriate feeding, serum Cu, Cp and oxidase activity were quite low a few weeks after birth, while a higher proportion of Cp-binding copper was found in the foals. This might be caused by the limited synthesis of ceruloplasmin in this period. These data suggest that newborn foals are in a critical situation of marginal copper status in the early stage of growth.

Aging↗

Evaluation of the catabolic activity of cartilage by measurement of serum keratan sulfate concentration in foals.

OBJECTIVES: To determine keratan sulfate (KS) concentration in the serum of foals at the early stage of growing, and to evaluate the role of serum KS as a cartilage catabolic marker, comparing its values with the fluctuation of serum alkaline phosphatase (ALP) activity as a measurement of osteoblastic activity. ANIMALS: 12 foals with normal growth and 3 foals with joint abnormalities within 18 months after birth. PROCEDURE: Measurement of KS concentration and ALP activity in serum and radiographic and physical examinations were done. RESULTS: In all foals, serum KS concentration was high from 1 week after birth to 3 months of age, while serum ALP decreased with aging. The value started to decrease rapidly from 3 to 5 months of age, then gradually reached adult values. During the first 3 months, KS concentration in male foals was significantly higher than that in female foals. In 3 foals which had joint problems, KS concentration was higher than that in normally growing foals at 1 week, and at 1, 2, and 3 months of age. CONCLUSIONS: Cartilage catabolic activity is higher in developing foals up to 3 months of age, suggesting that the immature joint at this time could be easily affected by any factor of loading. Moreover, though only 3 diseased foals were examined, higher serum KS concentration in these foals suggest that this variable might be a useful measure of joint diseases, even at an early stage of life in foals.

Aging↗

[Focal glomerular sclerosis in a sibling].

We described here one sibling with focal glomerular sclerosis. Proteinuria was noticed at the age of five in brother and four in sister. Both of them developed nephrotic syndrome shortly after the discovery of proteinuria. The nephrotic syndrome was resistant to corticosteroid, immunosuppressive agents or the combination of these drugs. Percutaneous renal biopsy in them revealed morphological and immunohistological features compatible to focal glomerular sclerosis. HLA typing in HLA-A, B, C and DR loci was identical to both. This observation suggests that genetic factors is associated with the pathogenesis of focal glomerular sclerosis.

Adolescent↗

Nucleotide sequence of cDNA to the rinderpest virus mRNA encoding the nucleocapsid protein.

The full-length cDNA corresponding to the mRNA encoding the nucleocapsid protein (NP) of rinderpest virus (RV) was cloned and its complete nucleotide sequence was determined. The gene of RV-NP was composed of 1683 nucleotides and contained a single large open reading frame, which is capable of encoding a protein of 525 amino acids with a molecular weight of 58,241 Da. The nucleotide sequence and predicted amino acid sequence were compared with those of measles virus (MV) and canine distemper virus (CDV). The nucleotide sequence of the coding region of RV-NP (53-1630) revealed a homology of 68.1% and 63.0% with MV and CDV-NP, respectively. Relatively moderate homologies of 68.7% (MV) and 64.3% (CDV) were found at nucleotides 53-592. The highest homology of 75.3-74.3% was equally present between RV and both MV and CDV in the middle region at nucleotides 593-1312. The homologies of the predicted amino acids in this region were 88.3% (MV) and 86.3% (CDV). Relatively low (MV) or little (CDV) homology was detected in the last 318 nucleotides toward the 3' terminus (1313-1630). The predicted secondary structures of amino acids at the C terminus differed between the three viruses.

Amino Acid Sequence↗

Immunological and virological characterization of improved construction of recombinant vaccinia virus expressing rinderpest virus hemagglutinin.

We constructed a recombinant vaccinia virus (RVV) expressing rinderpest virus (RPV) hemagglutinin (H) by modifying the promoter region of the original RVV. The promotor region was modified at three points, i.e., an outframe ATG was eliminated, the sequence between the promoter and initiation codon was shortened and the base sequence just upstream of the initiation codon was changed. As compared with the original RVV, the modified RVV was found to produce a remarkably large amount of H protein in infected rabbit kidney cells cultured in vitro and to induce high titers of anti-RPV-H antibodies in rabbits. The median protective doses in rabbits of the modified and of the original RVVs were 10(2) pfu and 10(3.5) pfu, respectively, indicating that the modified RVV was at least 10-times more effective in protection than the original. The neurovirulence of the modified RVV and the parental LC16mO strain was roughly at the same level, and was much lower than that of WR strain. The modified RVV was as heat-stable as the original one. These results indicate that the modified RVV could be a candidate rinderpest vaccine for further examinations including cattle.

Animals↗

[An optimum dose-finding study of HR810 (CPR) in chronic respiratory tract infections].

In order to determine the optimal dose of cefpirome sulfate (HR810, CPR) against respiratory tract infections (RTI), an optimal dose-finding study was conducted on cases of chronic RTI, and the clinical properties of the drug were compared with those of ceftazidime (CAZ). Inpatients with chronic RTI were randomly assigned to 3 groups: an HR 0.5 g group, receiving 0.5 g X 2/day of CPR an HR 1.0 g group, receiving 1.0 X 2/day of CPR and a CAZ group, receiving 1.0 g X 2/day of CAZ. As a rule, the drugs were administered by intravenous drip infusion for 14 days, after which period clinical efficacy, bacteriological response, safety, and utility were investigated. Of the total 121 cases, 106 were subject to analysis of clinical efficacy, including 38 cases in the HR 0.5 g group, 32 in the HR 1.0 g group, and 36 in the CAZ group. Efficacy rates in the assessment by the committee were 84.2% for the HR 0.5 g group, 75.0% for the HR 1.0 g group, and 86.1% for the CAZ group, without any significant difference between the 3 groups. The bacterial elimination rates were 73.9%, 75.0% m and 88.5%, respectively, without any significant difference between the 3 groups. Associated reactions were noted in 2 of 36 cases in the HR 1.0 g group (eruption and diarrhea), but not in the other 2 groups. The incidence of abnormal clinical laboratory findings was 23.1% in the HR 0.5 g group, 22.2% in the HR 1.0 g group, and 22.5% in the CAZ group, without any significant difference between the 3 groups. Utility rates were 84.2% for the HR 0.5 g group, 74.2% for the HR 1.0 g group, and 86.1% for the CAZ group, without any significant difference between the 3 groups. The HR 0.5 g and 1.0 groups showed no difference in clinical efficacy, bacteriological response, safety, and utility against RTI, and the results of both groups were about equal to those of the CAZ group.

Adolescent↗

[A case of intrapulmonary schwannoma that should be distinguished from lung cancer].

A 32-year-old woman was referred to our division because of abnormal shadow on a chest X-ray film taken at an annual health survey. Chest X-ray films and chest CT scanning revealed a smooth-surface mass at the left hilus. A bronchoscopic examination revealed severe extraluminal compression in the left basal bronchus but no visible tumors. Surgical treatment was performed on the suspicion of lung cancer. Since the intraoperative frozen section examination revealed a benign tumor, the tumor mass was resected. Based on intraoperative and pathological findings, benign intrapulmonary schwannoma associated with the left basal bronchus was diagnosed. Only 15 cases of intrapulmonary schwannoma have been reported in Japan.

Adult↗

[Foreign body-induced bronchial actinomycosis with severe stenosis that must be distinguished from lung cancer].

A 59-year-old woman who accidentally swallowed a foreign body (fish bone) 9 months ago was admitted to our hospital because of cough, hemosputum and sleep wheezing for two months. Chest roentgenograms and chest CT scanning revealed severe stenosis of the right lower lobe bronchus and truncus intermedius, suggesting lung cancer. Bronchoscopic examination revealed an intrabronchial foreign body. The biopsy specimen from granulation tissue revealed bronchial actinomycosis. The foreign body was removed bronchoscopically after an extensive chemotherapy with penicillin G (for actinomycosis) and prednisolone (for granulation tissue of the bronchus). This was considered to be a rare case of bronchial actinomycosis without a pulmonary lesion produced by a foreign body.

Actinomycosis↗

Development of heat-stable recombinant rinderpest vaccine.

Recombinant vaccinia virus (RVV) containing the full-length cDNA of rinderpest virus (RV)-haemagglutinin (H) gene was constructed. The H gene was inserted into the attenuated vaccine strain of vaccinia virus (VV), Le 16 m0, with two different promoters, namely cowpox virus A-type inclusion body (ATI) promoter or VV 7.5 kilodalton (P7.5) promoter. These RVVs produced the same sized fully glycosylated RV-H protein in RK 13 cells as that of the authentic RV-H. Their heat stability in the lyophylized state was similar to that of the parental VV. All rabbits immunized with these RVVs produced virus neutralizing (VN) antibody to RV as well as anti RV-H antibody. Four weeks after immunization, these animals were challenged with RV intravenously. None of the RVV-immunized rabbits developed any clinical signs of RV infection except one which was immunized with RVV containing the ATI promoter and developed low VN titer. These results indicate the possibility of developing a heat-stable recombinant vaccine for the eradication of rinderpest in tropical countries without cold storage systems.

Animals↗

Urinastatin (Kunitz-type proteinase inhibitor) reducing cisplatin nephrotoxicity.

The authors investigated the reductive effects of a Kunitz-type proteinase inhibitor, urinastatin, on the nephrotoxicity seen in lung cancer patients treated with cisplatin by measuring N-acetyl-beta-D-glucosaminidase (NAG) activity and beta 2-microglobulin (BMG) content in 24 hour urine, creatinine clearance, blood urea nitrogen (BUN), serum creatinine, uric acid, and BMG as factors of nephrotoxicity. In control patients treated with anticancer drugs containing cisplatin but no supplemental urinastatin, the 24 hour urine NAG and BMG levels increased more than three-fold over the pretreatment levels, 3 days after anticancer therapy, respectively. Creatinine clearance significantly decreased and levels of BUN, serum uric acid, and BMG in control patients significantly increased over the corresponding pretreatment levels, 3 days after anticancer therapy. However, supplemental urinastatin reduced abnormalities in levels of all these factors 3 days after therapy. These results suggest that supplemental urinastatin protects from cisplatin-induced nephrotoxicity, especially proximal tubular damage.

Acetylglucosaminidase↗

[A clinical evaluation of fluconazole in the treatment of deep mycosis].

Fluconazole is a novel triazole antifungal agent developed by Pfizer Inc. and available in both oral and intravenous forms. It is characterized by a long serum half-life of 25 to 30 hours and good absorbability into tissues. In the present study, fluconazole was given to 12 patients with deep mycosis orally, intravenously or by local infusion. The patients included 4 cases of candidemia, 1 case each of candidemia and candiduria, candiduria, esophageal candidiasis, Candida hepatic abscess, pulmonary cryptococcosis and septicemia due to unspecified yeasts and 2 cases of pulmonary aspergillosis. Clinical efficacies of fluconazole against these infections were excellent in 2 cases, good in 8 and fair in 2. None of the patients reported any side effects. From the results of the study, fluconazole appears to be a useful and safe drug for the treatment of deep seated mycosis.

Administration, Oral↗