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S Takeda

Publications and source records attributed to S Takeda.

At least 253 records · Page 14Linked to original sources

Involvement of lipid peroxidation in free fatty acid-induced isolated rat pancreatic acinar cell injury.

It was reported that free fatty acids degraded from triglycerides by lipase may play a major role in acute necrotizing or hyperlipidemia-induced pancreatitis. We hypothesized that this injury may be related to the peroxidation of cell membrane phospholipids and tested this hypothesis using isolated pancreatic acini. Pancreatic acini were prepared from male Sprague-Dawley rats by collagenase digestion. Linoleic acid was added (0.1-1.0 mM) to the acinar cell suspension to induce cell injury. Acinar cell damage was measured by lactate dehydrogenase release and by trypan blue exclusion. Phosphatidylcholine hydroperoxide and alpha-tocopherol in the acinar cells were measured. Protective effects of alpha-tocopherol (0.5, 5.0 mM) against this type of cell injury were also evaluated. When isolated acinar cells were treated with linoleic acid, a significant decrease in viability was observed in a time- and dose-dependent manner. In addition, the levels of phosphatidylcholine hydroperoxide after treatment of 0.5 mM of linoleic acid were increased and levels of alpha-tocopherol were decreased significantly. alpha-Tocopherol significantly ameliorated both cellular injury (p < 0.01) and increases in phosphatidylcholine hydroperoxide (p < 0.01). These data suggest that lipid peroxidation of the cellular membrane is an important component of the pancreatic cell injury mediated by free fatty acids.

Animals↗

Homologous recombination, but not DNA repair, is reduced in vertebrate cells deficient in RAD52.

Rad52 plays a pivotal role in double-strand break (DSB) repair and genetic recombination in Saccharomyces cerevisiae, where mutation of this gene leads to extreme X-ray sensitivity and defective recombination. Yeast Rad51 and Rad52 interact, as do their human homologues, which stimulates Rad51-mediated DNA strand exchange in vitro, suggesting that Rad51 and Rad52 act cooperatively. To define the role of Rad52 in vertebrates, we generated RAD52(-/-) mutants of the chicken B-cell line DT40. Surprisingly, RAD52(-/-) cells were not hypersensitive to DNA damages induced by gamma-irradiation, methyl methanesulfonate, or cis-platinum(II)diammine dichloride (cisplatin). Intrachromosomal recombination, measured by immunoglobulin gene conversion, and radiation-induced Rad51 nuclear focus formation, which is a putative intermediate step during recombinational repair, occurred as frequently in RAD52(-/-) cells as in wild-type cells. Targeted integration frequencies, however, were consistently reduced in RAD52(-/-) cells, showing a clear role for Rad52 in genetic recombination. These findings reveal striking differences between S. cerevisiae and vertebrates in the functions of RAD51 and RAD52.

Animals↗

A pedigree analysis with minimised ascertainment bias shows anticipation in Met30-transthyretin related familial amyloid polyneuropathy.

In type I familial amyloid polyneuropathy (FAP) caused by a variant Met30-transthyretin (TTR), genetic anticipation has been reported. To determine whether anticipation of the disease is a true biological phenomenon or the result of ascertainment bias, we compared age at onset of the affected child with that of the affected parent in 68 parent-child pairs (including data on assumed age at onset and on asymptomatic obligate heterozygotes and parents at obligate 50% risk) in 15 families. Excluding the parent-child pairs involving the proband and "bilineal pairs", onset occurred earlier in the child than in the transmitting parent in 60 out of 68 "unilineal pairs". After correction for ascertainment bias resulting from incomplete penetrance and reduced biological fitness in early onset patients, the number of anticipation pairs (60 pairs) was still significantly larger than that of non-anticipation pairs (29.7 pairs) (p < 0.05). When the children were sons, the difference in age at onset was significantly greater in the mother-son pairs than in the father-son pairs (p = 0.023). Although not all ascertainment biases could be eliminated, these data show strong evidence that anticipation in the transmission of Met30-TTR FAP is a true biological phenomenon.

Adolescent↗

Atrial natriuretic peptide enhances IL-1 beta-stimulated nitric oxide production in cultured rat vascular smooth muscle cells.

OBJECTIVE: To elucidate the effect of atrial natriuretic peptide (ANP) on cytokine-induced nitric oxide (NO) production, we examined whether ANP affects IL-1 beta-stimulated NO production and inducible NO synthase (iNOS) mRNA expression in cultured rat vascular smooth muscle cells (VSMC). METHODS: VSMC were incubated with test agents for 24 h. The nitrite concentration of the culture medium, a stable-end product of NO, was measured by the column reduction method. NOS mRNA expression was analyzed by Northern blotting. The intracellular cAMP content was measured by enzyme immunoassay. cAMP-dependent kinase (PKA) activity was determined by a PKA assay system. RESULTS: IL-1 beta stimulated nitrite production in VSMC. ANP (10 nM to 1 mM) enhanced the nitrite production and iNOS mRNA expression in the presence of IL-1 beta. Both 8-bromo-guanosine 3',5'-cyclic monophosphate (8-br-cGMP) and dibutylyl adenosine 3',5'-cyclic monophate enhanced IL-1 beta-induced nitrite production. The effects of these two nucleotide donors on the nitrite production were not additive, suggesting a common pathway. KT 5720, an inhibitor of PKA, abolished the enhancement of nitrite production by ANP and 8-br-cGMP, while KT 5823, an inhibitor of cGMP-dependent protein kinase, did not inhibit the enhancement. In the in vitro assay 8-br-cGMP increased PKA activity. CONCLUSIONS: ANP and cGMP enhanced IL-1 beta-induced NO production in VSMC. PKA rather than PKG may be involved in the enhancement.

Animals↗

Light chain deposition disease detected by antisera to a variable region of the kappa1 light chain subgroup.

A 59-year-old male started maintenance hemodialysis, and 80 months later died of congestive heart failure. Just before death he had no urine, and no monoclonal immunoglobulin could be demonstrated in the serum on immunoelectrophoresis. An autopsy showed deposition of periodic acid-Schiff-positive and Congo red-negative material in the interstitium and vessel walls of almost all organs and tissues. In the glomeruli there was a multifocal nodular accumulation of the material. Electron microscopy showed finely granular, not fibrillar deposits. In spite of these impressive lesions on light microscopy, the material was not stained with commercially available antisera to light chains. However, the material was positive for antisera to the variable region of the kappa1 light chain subgroup. This is the first case with light chain deposition disease that showed positive staining only with antisera to the variable region of the light chain.

Amyloidosis↗

Identification of Merkel cells by an antibody to villin.

Merkel cells represent a population of epithelial cells in the skin and oral mucosa. Although Merkel cells are reliably distinguishable from other epithelial cells at the ultrastructural level, these cells are usually not discernible by standard light microscopy and need special techniques for their identification. Villin is an actin-crosslinking protein that is associated with the actin filament cores of brush border microvilli. In this study we show that an antibody against villin is an excellent marker of Merkel cells and their microvilli even at the light microscopic level. The surrounding keratinocytes and subepithelial connective tissue cells do not show any significant affinity for the antibody against villin. Confocal laser micrographs reconstructed from serial images 0.5 microm thick of Merkel cells that were immunostained with villin clearly reveal the three-dimensional morphology of Merkel cells and their microvilli. The presence of villin in Merkel cell microvilli lends support to the idea that these cells might have a mechanoreceptor function.

Animals↗

Effect of nasal continuous positive airway pressure on pulmonary edema complicating acute myocardial infarction.

Cardiogenic pulmonary edema is a frequent cause of reparatory failure. We investigated the effects of nasal continuous positive airway pressure (CPAP) in patients with severe pulmonary edema associated with acute myocardial infarction. Twenty-nine consecutive patients were divided into 3 groups: firstly, 7 intubated patients who received mechanical ventilation at study entry comprised the intubation group. The rest of the patients were randomly assigned to either of the following 2 groups: 11 patients who received oxygen plus CPAP delivered by a nasal mask (CPAP group), and 11 patients who received oxygen only via face mask (oxygen group). All patients in the intubation group had cardiogenic shock. Two patients (18%) in the CPAP group and 8 patients (73%) in the oxygen group required mechanical ventilation with endotracheal intubation (p=0.03). The hospital mortality rate in the CPAP group (9%) was significantly lower than the oxygen group (64%, p=0.02). The pulmonary artery wedge pressure and heart rate were significantly lower in the CPAP group than in the oxygen group 24 h after study entry (p<0.05 and p<0.01). The mean pulmonary artery pressure 48 h after study entry was 18+/-5 mmHg in the CPAP group and 25+/-8 mmHg in the oxygen group (p<0.05). The PaO2/FiO2 ratio increased in the intubation group (168+/-69 to 240+/-57, p<0.05) and the CPAP group (137+/-17 to 253+/-67, p<0.01) 24 h after study entry. Arterial plasma endothelin-1 concentrations decreased significantly earlier in the CPAP group than in the oxygen group (p<0.05). In patients without cardiogenic shock, nasal CPAP lead to an early improvement in oxygenation and hemodynamics, and decreased the mortality rate. Early and active respiratory management is recommended in patients with pulmonary edema associated with acute myocardial infarction.

Aged↗

Exercise-induced monomorphic ventricular tachycardia from the left ventricle outflow tract.

A case of exercise-induced idiopathic ventricular tachycardia (VT) arose from the left ventricular outflow tract. The QRS morphology of the VT was Rs pattern in V1 and R pattern in the lateral leads with inferior axis. The pacing at the superior interventricular septum near the mitral anulus produced the best pace mapping. Radiofrequency application to this site suppressed the VT.

Exercise↗

Methylprednisolone pulse therapy in two clinical types of crescentic glomerulonephritis.

To clarify the effectiveness of methylprednisolone pulse therapy on crescentic glomerulonephritis (CresGN), data of 46 patients was retrospectively studied. According to the slope of reciprocals of serum creatinine (s-Cr) the patients were divided into acute and insidious types, and each type was further divided into pulse (P) and conventional (C) therapy groups. In group C, s-Cr improved more frequently in the acute type (8/10) than in the insidious type (1/9, p<0.05), and the renal survival rate was somewhat higher in the former (p=0.09). In the acute type there was no difference in the improvement rate of s-Cr between the two therapy groups, whereas in the insidious type, the improvement rate was higher in group P (9/15) than in group C (1/9, p<0.05) and the renal survival rate was higher in the former (p<0.01). These results suggest that methylprednisolone pulse therapy may be highly effective for the insidious type of CresGN.

Acute Disease↗

Superior sagittal sinus thrombosis associated with primary antiphospholipid syndrome--case report.

A 36-year-old female with a history of recurrent pregnancy loss experienced sudden onset of disturbance in consciousness, with right hemiparesis and total aphasia. Computed tomography revealed a massive hemorrhage in the left frontal lobe, and angiography showed occlusion of the anterior two-thirds of the superior sagittal sinus. Laboratory investigations detected the presence of lupus anticoagulant, elevation of the anticardiolipin beta 2-glycoprotein I complex antibody level, and a decreased protein S activity level. There were no underlying conditions, such as connective tissue disorders, malignancies, infectious diseases, and drug-induced disorders, so the diagnosis was primary antiphospholipid syndrome. Primary antiphospholipid syndrome should be considered in the evaluation of patients with "idiopathic" or "primary" sinus and cerebral venous thrombosis.

Adult↗

[Nutritional intake by the oldest elderly Japanese. Tokyo Centenarian Study 6].

Rapid demographic aging has made caring for the elderly an increasingly important social issue in Japan. To study current conditions of the oldest elderly citizens, we investigated the dietary practices of centenarians in the Tokyo metropolitan area. First, we compared the food intake of centenarians with that of octogenarians. Next, to identify dietary trends, we investigated whether food intake by centenarians had changed significantly between 1981 and 1995. Nutritional intake by the centenarians and octogenarians in 1995 was about 60% and 75% that of the control, respectively. However, the nutritional intake of well nourished centenarians was similar to that of the octogenarians. Cognitive function and daily activity have an influence on nutritional intake. The centenarians were similar to the control subjects in their consumption of dairy products, sweets, and fruit. However, their intake of cereals, meat, fish, and fatty oils was loss than 60% that of the control, which indicates their preference for soft and sugary foods. The pattern of dietary practices of centenarians in 1981 was similar. Although the total food intake of centenarians amounted to 60% of the control in 1995 energy intake per kilogram of body weight averaged over 30 kcal. As to dietary trends, centenarians in 1981 are more cereals, eggs, algae products, and legumes than did their 1995 counterparts. This finding seems to reflect a generational difference in dietary habits.

Activities of Daily Living↗

Preclinical antitumor efficacy of S-1: a new oral formulation of 5-fluorouracil on human tumor xenografts.

S-1 is a new oral formulation of 5-fluorouracil (5-FU) consisted of 1M tegafur, 0.4M 5-chloro-2,4-dihydroxypyridine that inhibits a degradation of 5-FU, and 1M potassium oxonate that regulates the phosphorylation of 5-FU in the gastrointestinal tract, and has shown excellent antitumor efficacy against various murine tumors in rodents, compared to the oral tegafur-based antitumor drug, UFT (1M tegafur plus 4M uracil), which is used clinically in Japan. To assess the possibility of clinically using S-1, we investigated the antitumor effect of S-1 on various human solid tumor xenografts in athymic rats and mice. In the nude rat system, S-1 was significantly effective against all 12 tumor xenografts tested when its minimum toxic dose (15 mg/kg) was administered for 14 days. Three tumors, stomach (H-81), colon (KM12C) and breast (H-31) markedly regressed in response to treatment with S-1 but not with UFT. The antitumor potency of S-1 was weak against human tumors xenografted into nude mice and likely similar to that of UFT. The reason of the discrepancy in the efficacy of S-1 between rats and mice was found to be that the 5-FU levels in the blood and tumor tissue of rats after oral administration of S-1 persisted much longer than in mice, and this prolonged maintenance of plasma 5-FU levels was significantly related to the potent antitumor activity of S-1. In conclusion, the results of this study suggested that based on its biological and pharmacokinetic characteristics, oral S-1 should be active against various human cancers.

Administration, Oral↗

Molecular cloning of the chick Nau gene and analysis of its expression patterns during neurogenesis.

We have previously identified a novel gene, Nau (Neuron-specific gene, which has a number of AU-rich RNA instability motifs), from a quail spinal cord cDNA library. Nau expression was observed mainly in post-mitotic neuroblasts, especially in the stage of axonogenesis. In this study, we cloned its chick orthologue (cNau, 5069 bp), which encodes 369 amino acid residues. cNau's open reading frame has three highly conserved regions with rat STOP (stable tubule-only polypeptide). cNau may be an orthologue of STOP gene considering its uniqueness in zoo blot analysis and its sequence similarity. Both the genetic structure and temporo-spatial expression patterns indicate that the cNau gene may be related to axonogenesis. In the hindbrain, cNau mRNA was accumulated in rhombomere boundary regions and in the rhombomere 2, 4 and 6. These observations suggest a specific role of cNau in the hindbrain or the difference in development between the hindbrain and spinal cord.

Amino Acid Sequence↗

[Phase I study of orally administered UFT plus l-leucovorin].

A Phase I study of UFT plus l-LV was conducted in 29 patients (pts) with G.I. cancer on a multicenter cooperative study. UFT and l-LV were given orally in two divided doses for 28 consecutive days, followed by a 14 day-rest period. UFT was fixed in three doses, 250, 313 and 375 mg/m2/day, and l-LV was increased in dose from 25 to 50 and to 100 mg/body/days. Dose-limiting toxicities were anorexia, diarrhea, and nausea/vomiting. The maximum tolerated dose of UFT was 375 mg/m2/day, and l-LV 25 mg/body/day. Severe myelotoxicity was not observed. There were three responders (PR) out of 21 pts with measurable disease at UFT doses of 313 mg/m2/day and l-LV 50 and 100 mg/body/day. Responses observed were abdominal mass (rectal ca), liver metastasis (pancreas ca) and metastasis of liver and lymph-node (gastric ca). As a result of pharmacokinetics, plasma concentrations of 5-methyl-THF were maintained > 1.0 microM for over 5 hours that was considered to have a modulating effect on the plasma concentration. In doses of 50 mg and 100 mg/body/day of l-LV. No accumulations in plasma were observed in patient treated in 28 days by l-LV/UFT therapy. It was suggested UFT and l-LV did not interfere with each other's absorption. A Phase II study is recommended, with doses of 313 mg/m2/day of UFT and 50 or 100 mg/body/day of l-LV.

Administration, Oral↗

[A case of bow hunter's stroke caused by bilateral vertebral artery occlusive change on head rotation to the right].

We report a case of bow hunter's stroke caused by simultaneous bilateral vertebral artery occlusive changes at the right C3-4 and the left C1-2 level on head rotation to the right side. The pathogenesis and surgical treatment for this particular case are discussed. A 61-year-old male with cervical spondylosis repeatedly experienced vertebrobasilar insufficiency when he rotated his head over 60 degree from the mid-position to the right side. Bilateral vertebral angiography demonstrated severe compression of the right vertebral artery by a lateral osteophyte and instability at the C3-4 level accompanied with the mechanical stenosis of the left vertebral artery at the C1-2 level only at the time of turning his head to the right. As the surgical treatment we performed osteophytectomy of the right uncovertebral joint at the C3-4 level in addition to anterior decompression with fusion using hydroxyapatite spacer and titanium plate at that level. Postoperatively, the patient had no ischemic episodes and there was angiographical resolution of the rotational stenosis at the C3-4 level. For the clinical manifestation of bow hunter's stroke on head rotation, it is indispensable that simultaneous severe occlusive changes present on bilateral vertebral arteries. In case of a vertebral occlusive change caused by lateral osteophyte at the unstable vertebral joint, anterior decompression and fusion with osteophytectomy may be a wiser approach than arterial decompression or posterior fusion at the C1-2 level to another vertebral artery occlusive lesion.

Cerebrovascular Disorders↗

How often do we operate too late in aortic stenosis?

The management of asymptomatic severe aortic stenosis remains controversial. Despite a good outcome in terms of mortality, the left ventricle may not recover fully after aortic valve replacement and patients may have impaired exercise ability. Routine assessment of the left ventricle is dominated by transverse systolic function to the relative neglect of long-axis and diastolic function. Long-axis dysfunction develops earlier than transverse dysfunction and may correlate with exercise ability. Reported symptoms can be unreliable and exercise testing reveals significant limitation in many apparently asymptomatic patients. Exercise testing and echocardiographic markers of early LV systolic dysfunction may help to refine the timing of surgery in patients with apparently asymptomatic severe aortic stenosis.

Aortic Valve Stenosis↗

[A case of male who was taken systemic lupus erythematosus with chilblain lupus].

A 38-year-old male was admitted to our hospital because of high grade fever, erythema of face and extremities and oral ulcer. The laboratory examination showed leukopenia, high titer (320 dil.) of antinuclear antibody, a positive reaction of anti-Sm antibody. Especially histopathology of hand erythema showed hydrophilic degeneration consist with chilblain lupus. Because his symptoms were consistent with the criteria of American College of Rheumatology (1982), he was diagnosed as systemic lupus erythematosus (SLE). After administration of 60 mg prednisolone daily, the symptoms gradually improved. Any recrudescence of serological abnormalities or clinical symptoms was not observed until now, although chilblain lupus still persisted. Originally SLE is frequent in young female and often attended with renal disease, central nerve disease and serositis. We reported a case of middle-aged male who developed SLE with chilblain lupus which was rare skin lesion of SLE without severe organic lesion and discussed the relation among chilblain lupus, discoid lupus erythematosus (DLE) and SLE.

Adult↗