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Biomedical subjects

S Takeuchi

Publications and source records attributed to S Takeuchi.

At least 325 records · Page 18Linked to original sources

Inhibition by SK&F96365 of NO-mediated relaxation induced by Ca2(+) -ATPase inhibitors in rat thoracic aorta.

1. We investigated the effect of SK&F96365, a putative inhibitor of receptor-operated Ca2+ entry, on the endothelium-dependent, NO-mediated relaxation and cyclic GMP formation induced by Ca2(+)-ATPase inhibitors in rat thoracic aorta. 2. SK&F96365 inhibited cyclopiazonic acid or thapsigargin-induced relaxation and cyclic GMP formation mediated by a constitutive NO synthase, which is known to be activated by the Ca2+ that enters into the endothelial cells via plasma membrane Ca2+ channels subsequent to depletion of stored Ca2+ by Ca2(+)-ATPase inhibitors. 3. SK&F96365 also inhibited relaxation and cyclic GMP formation induced by acetylcholine, without affecting those induced by nitroprusside and A23187. 4. Ni2+ attenuated relaxation and cyclic GMP formation induced by cyclopiazonic acid and acetylcholine. 5. In contrast, the voltage-dependent Ca2+ channel blocker, nifedipine, did not affect the relaxation caused by Ca2(+)-ATPase inhibitors. 6. These results suggest that endothelium-dependent, NO-mediated relaxation of the arteries induced by Ca2(+)-ATPase inhibitors is triggered by the Ca2+ that enters into endothelial cells via receptor-operated channels (SK&F96365-sensitive channels) subsequent to depletion of stored Ca2+ as a result of inhibition of the Ca2(+)-ATPase (Ca2+ pump) of the stores.

Animals↗

[A case of amoebiasis as a latent infection].

A 69-year-old male was admitted because of constipation and abdominal distension. A colon fiberscopic examination revealed the formation of ulceration. The trophozite of Entamoeba histolytica was detected from from the specimens of colon mucosal biopsy of the ulcer. The stool was positive for the cysts of E. histolytica too. He had been in China and Southeast Asia during World War II. He returned home and experienced amoebic dysentry, and was treated with Emethin hydrochlolide. He suffered from amoebic disentry in 1970 and was treated with Emethine hydrochrolide again. After the War he had not gone abroad, and was not a homosexual. So this case was considered a latent infection of E. histolytica from the War. This time he was treated with metronidazol and minocycline. After the therapy, cysts were negative in the stool and the ulcer was cured on the colon fiberscopic examination.

Aged↗

Detection of toxic shock syndrome toxin-1 gene in Staphylococcus aureus bovine isolates and bulk milk by the polymerase chain reaction.

Staphylococcus aureus isolates from mastitic cow's milk and farm bulk milk were examined for toxic shock syndrome toxin-1 (TSST-1) gene (tst gene) by the polymerase chain reaction (PCR). The 179 bp band of tst gene was observed in almost all the bovine isolates which showed TSST positive in a latex agglutination, as well as in human strain FRI 1169, but was not observed in bovine isolates of TSST negative. The lowest detectable threshold of the PCR for tst gene was 1.2 x 10(3) cells/ml. When 125 bovine milk samples were cultured selectively for staphylococci and examined by PCR, the tst gene was detected in 10 of the 35 culture fluids, in which staphylococci were recognized by Gram's staining.

Animals↗

Acoustic neurinoma with a large organized hematoma--case report.

A 66-year-old female presented with a large organized hematoma within an acoustic neurinoma. She had suffered from diminished hearing for 20 years and had headache 1 week before presentation. Computed tomography demonstrated an inhomogeneously high density cerebellopontine angle mass, and magnetic resonance imaging showed a mass with heterogeneous intensity and gadolinium-diethylenetriaminepenta-acetic acid enhancement of only the peripheral surface of the mass and the inner parts of the internal auditory meatus. At operation the majority of the mass was soft and feature-less with a firm capsule, and a yellowish soft tumor was removed from the perimeatal area. Histological examination showed the mass was an acoustic neurinoma with a large organized hematoma. Extensive hemorrhage from an abnormal vascularity in the tumor had repeated followed by granulomatous organization.

Aged↗

Ultra-early rebleeding in spontaneous subarachnoid hemorrhage.

To determine the incidence of, and risk factors for, the occurrence of rebleeding between admission and early operation (ultra-early rebleeding) in patients with spontaneous subarachnoid hemorrhage (SAH), the authors reviewed the cases of 179 patients admitted within 24 hours after their last attack of SAH. Thirty-one (17.3%) of these patients had ultra-early rebleeding despite scheduling of early operation (within 24 hours after admission). The incidence of rebleeding significantly decreased as the time interval between the last attack and admission increased. Patients with rebleeding before admission, high systolic blood pressure, intracerebral or intraventricular hematoma, those in poor neurological condition on admission, and those who underwent angiography within 6 hours of the last SAH were significantly more likely to have ultra-early rebleeding than those without these factors. The incidence of rebleeding also significantly increased as levels of enhancement of platelet sensitivity and thrombin-antithrombin complex increased. Multivariate analysis revealed that the following three factors were independently associated with ultra-early rebleeding: the level of enhancement of platelet sensitivity; the time interval between the last attack and admission; and the level of thrombin-antithrombin complex. On the basis of these findings, the authors suggest that many of the risk factors for ultra-early rebleeding are interrelated. A particularly high risk of ultra-early rebleeding was observed in those patients 1) who had platelet hypoaggregability; 2) who were admitted shortly after their last SAH; and 3) whose thrombin-antithrombin complex levels were extremely high and were thus in severe clinical condition.

Cerebral Angiography↗

[Malignant fibrous histiocytoma of spermatic cord: a case report].

A 52-year-old man presented with a painful, gradually enlarging mass in the left inguinal region. An ultrasound examination demonstrated a lobulated, heterogenous tumor 6.0 x 4.0 x 3.0 cm in diameter, which separated from the left testis and epididymis. Radical inguinal orchiectomy with wide en bloc local resection was performed. Histologic diagnosis was a malignant fibrous histiocytoma (MFH) with a giant cell variant. The patient underwent postoperative regional irradiation and has been alive without metastasis and local recurrence 3 months after the operation. Among the 19 patients with MFH of spermatic cord reported in Japan, only two cases were of giant cell type of MFH including the present case.

Genital Neoplasms, Male↗

[Clinical significance of serum soluble interleukin-2 receptor (sIL-2R) determination in patients with rheumatoid arthritis].

It has been recently shown that soluble interleukin-2 receptor (sIL-2R) is related to the pathogenesis of autoimmune diseases. We determined serum levels of sIL-2R in patients with rheumatoid arthritis (RA). Fifty-three patients (3 males and 50 females from 35 to 70 years old) and sex- and age-matched 50 healthy subjects were included in this study. The sIL-2R concentrations positively correlated with Lansbury index of RA (r = 0.602, p < 0.01). There was a significant correlation between sIL-2R levels and the prevalence of CD3+.HLA-DR+ lymphocytes (r = 0.420, p < 0.01).

Adult↗

[Amyloidosis secondary to bronchiectasis].

A 77-year-old woman was hospitalized repeatly due to frequent hemoptysis and production of bloodly sputum for several years. Bronchography in 1989 revealed bronchiectasis. She had complained of abdominal pain and diarrhea since 1991, and her urine was first positive for protein in 1992. She was admitted to our hospital in October 1992 because of edema, anemia, and hypoproteinemia. Despite treatment, renal dysfunction and the gastrointestinal disorder progressed and she died in January 1993. An autopsy revealed diffuse depositions of amyloid in many organs, especially in the kidney and the gastrointestinal tract. This amyloid protein was identified as AA protein, which was suggestive of secondary amyloidosis. Bronchiectasis appears to have been the disease underlying this patient's amyloidosis.

Aged↗

[Surgery for bone metastasis of testicular tumor: a case report].

A 31-year-old man was admitted to our hospital with the chief complaint of painful right scrotal swelling. Based on the diagnosis of right testicular tumor with multiple lung metastasis and L2 vertebral body metastasis, right high orchiectomy and three courses of chemotherapy (peplomycin, etoposide, CDDP) were performed. Histological diagnosis was teratocarcinoma. With the complete remission for lung metastasis and no change for bone metastasis, L2 spondylectomy and additional four courses of the same chemotherapy were performed. The patient has been free of the disease for 11 months after the spondylectomy.

Adult↗

Urinary pyridinoline and deoxypyridinoline as potential markers of bone metastasis in patients with prostate cancer.

PURPOSE: The levels of probable markers of bony metastatic disease were measured to evaluate their efficacy as predictors of disease and therapeutic outcome. MATERIALS AND METHODS: Urinary pyridinoline, urinary deoxypyridinoline, serum alkaline phosphatase and serum osteocalcin were measured in patients with benign prostatic hyperplasia, clinically localized prostate cancer and prostate cancer with bone metastases. Also, urinary pyridinoline and deoxypyridinoline were compared in 2 groups of patients with metastatic prostate cancer of the bone who demonstrated progression or positive response to treatment. Urinary pyridinoline and deoxypyridinoline were determined by high performance liquid chromatography and were normalized to urinary creatinine. RESULTS: Levels of pyridinoline and deoxypyridinoline in urine, and the level of alkaline phosphatase in serum from patients with bone metastatic prostate cancer were significantly greater than levels in patients with benign prostatic hyperplasia or localized prostate cancer. Serum osteocalcin levels failed to separate the 3 groups. Serial measurement of urinary pyridinoline and deoxypyridinoline was correlated with a positive response to treatment (decreased) and with clinical progression of disease (increased) before detection of new bone lesions by bone scintigraphy. CONCLUSIONS: Measurement of urinary pyridinoline and deoxypyridinoline may provide a useful marker of prostate cancer metastatic to bone and may be useful in monitoring the response to treatment.

Aged↗

Complete recanalization via fibrinolytic therapy can reduce the number of ischemic territories that progress to infarction.

PURPOSE: To clarify the clinical significance of fibrinolytic therapy for acute ischemic stroke. METHODS: We analyzed findings in 18 patients with occlusion of a major artery in respect to cerebral blood flow thresholds for infarction. Nine of these patients had shown complete recanalization just after the treatment, between 3.5 and 7.25 hours after symptom onset, and the other nine had shown no change. Cerebral blood flow was measured by single-photon emission CT using 99mTC-labeled hemamethylpropyleneamine oxime and assessed semiquantitatively: multiple regions of interest were placed on the section images and two parameters, the R/CL ratio and the R/CE ratio, were calculated (where R represents a mean count of the region of interest in the affected hemisphere, CL on the opposite side, and CE in the cerebellar hemisphere on the affected ischemic side). RESULTS: Reperfusion significantly reduced the development of infarction in the regions of interest with an R/CL ratio between 0.65 and 0.85 or an R/CE ratio between 0.55 and 0.75. No correlation was observed between the development of infarction and the duration of ischemia. The cerebral blood flow threshold in patients without recanalization was higher than that in patients with recanalization. CONCLUSION: Reperfusion achieved by fibrinolytic therapy in the acute stage can save ischemic brain within a limited cerebral blood flow value.

Aged↗

Alterations of the cyclin-dependent kinase inhibitor p19 (INK4D) is rare in hematopoietic malignancies.

Cyclin-dependent kinase inhibitors (CDKIs) can be classified into two groups based on the structure of the proteins. One group includes the p21 (CIP1, WAF1, CAP20), p27 (Kip1), and p57 (Kip2) CDKIs, which contain a homologous amino-terminal cyclin-dependent kinase (cdk) inhibitory domain. The p16 (INK4A), p15 (INK4B), and p18 (INK4C) CDKIs, which have an ankyrin repeat motifs, belong to the other group. The p16 and p15 CDKI genes are very frequently altered in a variety of cancers including hematopoietic malignancies. The p19 (INK4D) gene is a newly cloned CDKI which belongs to the latter group. To determine if p19 genetic alterations play a role in hematopoietic malignancies, we examined DNA from 45 childhood newly diagnosed acute lymphocytic leukemias (ALLs), 30 acute myeloblastic leukemias (AMLs), 10 chronic myelocytic leukemias (CMLs), 45 adult T cell leukemias (ATLs), 70 non-Hodgkin's lymphomas (NHLs), and 20 multiple myelomas (MM) as well as 14 ALL, 20 AML, two ATL, and five lymphoma cell lines. Using Southern blot analysis, one homozygous deletion of the p19 gene was detected in a human immunodeficiency virus (HIV)-related Burkitt-like lymphoma sample. No point mutations in any of the samples were found by polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) analysis. Our investigation suggests that alterations of p19 do not play an important role in the development of most hematopoietic malignancies.

Base Sequence↗

[Left ventricular pseudoaneurysm recognized 9 years after mitral valve replacement and repeated heart failure of 3 years duration: a case report].

A 66-year-old woman had suffered from repeated heart failure beginning 6 years after mitral valve replacement. Left ventricular pseudoaneurysm was discovered 9 years after the replacement, while no evidence including histology was obtained for the cause of the pseudoaneurysm except the mitral valve replacement. The progression of aortic valve stenosis and the formation of the pseudoaneurysm may have contributed to the onset of congestive heart failure. Surgical treatment was successful. Although left ventricular pseudoaneurysm after mitral valve replacement is rare, careful echocardiographic examination is necessary for detecting such a complication in patients after surgery.

Aged↗

[A new look at the history of tumor immunotherapy--for its fruitful future through overcoming the widespread cynicism].

This review deals with a new look at the history of tumor immunotherapy by dividing that into four generations in the context of its recent scientific advance which gives a birth of a new paradigm to immunology and immunotherapy of human cancer. Tumor immunology was born in 1953 when the presence of tumor specific transplantation antigens was demonstrated in the animal models. All trials were nonsense in the 0 generation before its birth except for Coley's vaccine. The 1st generation (1953-1983) of immunotherapy after its birth was the period in which the nonspecific immunotherapy was enthusiastically attempted too much without knowledge of specific tumor immunity, only to result in the cynicism of tumor immunology and immunotherapy. After this, new important discoveries in tumor immunology have been followed successively in animal models, giving a scientific basis to immunotherapy of human cancer. The key discoveries in human tumor immunology, however, have been done since 1986 when first adoptive immunotherapy with autologous CTL from patient's tumor was attempted. Thus, immunotherapy from 1983 to 1986 and that from 1986 to present are separately reviewed in this paper as the 2nd generation and the 3rd generation, respectively.

Humans↗

Allelotype analysis of childhood acute lymphoblastic leukemia.

To identify the genetic events that may play an important role in leukemogenesis of childhood ALL, we report for the first time the allelotyping of childhood ALL. Twenty-four cases of childhood ALL were screened for loss of heterozygosity (LOH) using 101 highly polymorphic microsatellite markers, which are distributed among all autosomal chromosomes. For LOH analysis on both chromosomes 9 and 12, 54 childhood ALL samples were examined. The most frequent allelic loss was found on chromosomal arm 9p, where 20 of 50 (40%) informative samples showed LOH. Moreover, nearly 30% of samples that did not have either homozygous deletions or point mutations of the putative tumor suppressor genes CDKN2/INK4A/p16 and INK4B/p15 on chromosomal arm 9p had LOH at D9S171. Loss of chromosomal arm 12p was also frequent (26%). Mutational analysis suggested that the altered gene on 12p is not the cyclin-dependent kinase inhibitor p27/Kip1, which is also on 12p. Several other regions that had LOH included 1p, 4q, 5p, 6q, 7p, 8p, 9q, 10q, 13q, 17p, 17q, 18q, 19q, and 22q. Of 24 patients, 19 (79%) showed allelic loss on at least one chromosomal arm. Samples of two patients (8%) showed LOH on almost all chromosomes. Fractional allelic loss, calculated for each sample as the total number of chromosomal arms lost/total number of arms with information, showed a median value of 0.04 and a mean of 0.123 (range, 0 to 0.95). This fractional allelic loss is lower than those reported for many solid tumors. This analysis shows the extreme power of LOH analysis using microsatellite markers in childhood ALL.

Adolescent↗

High incidence of ultraviolet-B-or chemical-carcinogen-induced skin tumours in mice lacking the xeroderma pigmentosum group A gene.

Xeroderma pigmentosum (XP) is an autosomal recessive disorder characterized by a high frequency of skin cancer on sun-exposed areas, and neurological complications. XP has a defect in the early step(s) of nucleotide-excision repair (NER) and consists of eight different genetic complementation groups (groups A-G and a variant). We established XPA (group-A XP) gene-deficient mice by gene targeting of mouse embryonic stem (ES) cells. The XPA-deficient mice showed neither obvious physical abnormalities nor pathological alterations, but were defective in NER and highly susceptible to ultraviolet-B- or 9,10-dimethyl-1,2-benz[a]anthracene-induced skin carcinogenesis. These findings provide in vivo evidence that the XPA protein protects mice from carcinogenesis initiated by ultraviolet or chemical carcinogen. The XPA-deficient mice may provide a good in vivo model to study the high incidence of skin carcinogenesis in group A XP patients.

9,10-Dimethyl-1,2-benzanthracene↗

Analysis of a family of cyclin-dependent kinase inhibitors: p15/MTS2/INK4B, p16/MTS1/INK4A, and p18 genes in acute lymphoblastic leukemia of childhood.

A newly recognized family of proteins that inhibit cyclin-dependent kinases (CDKs) termed cyclin-dependent kinase inhibitors (CDKI) have an important role in regulation of cell-cycle progression. A subfamily of these CDKIs (p15INK4B/MTS2, p16INK4/MTS1, and p18) have a high degree of structural and functional homology and are candidate tumor-suppressor genes. We evaluated the mutational status of the p15, p16, and p18 genes in 103 childhood acute lymphoblastic leukemia (ALL) samples and correlated these results with both their clinical data and additional results concerning their loss of heterozygosity in the region of the p15/p16 genes. Homozygous deletions of the p16 gene occurred extremely frequently in T-ALLs (17/22; 77%), and it was also frequent in precursor-B ALLs (12/81; 15%). Homozygous deletions of the p15 gene were also very frequent in T-ALLs (9/22; 41%), and it occurred in 5 of 81 (6%) precursor-B ALL samples. No deletions of p18 was found in any of the 103 ALL samples. Also, no point mutations of the p15, p16, and p18 genes were detected. We correlated p15/p16 alterations at diagnosis with their clinical characteristics as compared with 2,927 other patients treated similarly. Those with p15/p16 alterations were older; had higher white blood cell counts, often with T-cell ALL phenotype; and more frequently had a mediastinal mass at presentation; but they had the same nonremission, relapse, and survival rates at 5 years as did those patients whose blast cells did not have a p15/p16 deletion. To better understand the extent of alterations affecting chromosome 9p21 (location of the p15/p16 genes), loss of heterozygosity (LOH) was examined at D9S171, which is about 1 megabase proximal to the p15/p16 genes. LOH was detected in 15 of 37 (41%) informative samples. Interestingly, of the 24 informative samples that had no detectable alteration of the p15/p16 genes, 7 samples (29%) had LOH at D9S171. In summary, we show in a very large study that p15 and p16, but not p18, CDKI genes are very frequently altered in ALL; those with p15/p16 alterations are more frequently older children, have higher white blood cells at presentation, and often have a T-cell ALL phenotype. The LOH analysis suggests that another tumor-suppressor gene important in ALL also is present on chromosome 9p21.

Age Factors↗