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T Sugimoto

Publications and source records attributed to T Sugimoto.

At least 145 records · Page 8Linked to original sources
PubMed2001

[A case of systemic lupus erythematosus with hemophagocytic syndrome and cytophagic histiocytic panniculitis].

A 23-year-old man, admitted because of high fever, polyarthralgia, butterfly rash and chest pain, was diagnosed as systemic lupus erythematosus (SLE) from the findings of positive antinuclear antibody and anti-DNA antibody. He was treated with 60 mg prednisolone daily, but as reducing the dose, white blood cell counts and platelet counts were decreased and fever, polyarthralgia, decrease of complements, increase of ferritin, hepato-splenomegaly and liver dysfunction were observed. Bone marrow specimen revealed phagocytosis of blood cells by histiocytes and he was diagnosed as hemophagocytic syndrome(HPS) due to active SLE. Methylprednisolone pulse therapy was effective temporarily, HPS recurred while reducing steroid, and cyclosporin was added. After a temporary remission, marked extensive swelling in the face appeared suddenly. Facial skin biopsy showed necrosis of fat cells and hemophagocytosis by histiocytes. Accordingly, he was diagnosed as panniculitis due to HPS and was treated successfully with intravenous cyclophosphamide pulse therapy and high dose of gammaglobulin. Several cases of HPS due to SLE have been reported recently, but this is a rare case of cytophagic histiocytic panniculitis (CHP) due to SLE.

Adult↗
PubMed2001

Diagnosis of deep vein thrombosis using platelet scintigraphy.

PURPOSE: We reviewed the usefulness of platelet scintigraphy, in which autologous platelets labeled with indium-111-oxine reveal thrombotic activity, for evaluating deep vein thrombosis (DVT). MATERIALS: During the past 2 years, 39 cases with DVT were enrolled in this study. DVT was definitely diagnosed by color duplex scanning, platelet scintigraphy or both in all cases. For semiquantitative analysis, we estimated the ratio of accumulation in the abnormal region to that in the normal vein on the other side, and defined an abnormal accumulation ratio as over 1.2. RESULTS: Abnormal accumulation ratio showing active DVT was recognized in 30 cases (77%), and showed a good correlation with clinical symptoms. In addition, in 19 cases with crural DVT, platelet scintigraphy showed abnormal accumulation ratio in 16 cases (84%), while duplex scanning detected thrombi in 13 cases (68%). In cases with abnormal accumulation ratio, thrombolytic and anticoagulant therapy were very effective for improving clinical symptoms as well inducing regression of the accumulation ratio. CONCLUSIONS: Platelet scintigraphy was very useful for the diagnosis and treatment of DVT and for evaluation of the effect of anticoagulant therapy. Limitations in the definite diagnosis of deep vein thrombosis (DVT) have been apparent for more than three decades. During the last decade, duplex scanning has reached a high level of accuracy and has been considered the gold standard in the diagnosis of DVT, instead of venography. However, duplex scanning and venography demonstrates only the anatomic alterations associated with venous lesions. In contrast, in platelet scintigraphy, the labeled platelets are incorporated directly into the thrombus and can reveal thrombus activity. We noticed that autologous platelets labeled with indium-111-oxine accumulated on fresh lesions of DVT. This observation suggested two applications of this technique: 1) evaluation of the role of platelets in the pathophysiologic characteristics of DVT; and 2) monitoring the effects of anticoagulant therapy.

Adult↗
PubMed2001

Studies on mechanisms of low emetogenicity of YM976, a novel phosphodiesterase type 4 inhibitor.

YM976 is a novel and selective inhibitor of phosphodiesterase type 4 (PDE4) with a different chemical structure from rolipram. Orally administered YM976 showed anti-inflammatory activity (ED(50) = 2.8 mg/kg) similar to rolipram (3.5 mg/kg). On the other hand, the emetogenicity of YM976, one of the main adverse effects of PDE4 inhibitors, was lower (maximal non-emetic dose = 10 mg/kg) than that of rolipram (1 mg/kg). The reasons for this low emetogenicity of YM976 remain unclear, and the present study endeavored to elucidate the mechanisms. Candidates for the possible mechanisms included 1) PDE4 subtype selectivity, 2) binding affinity for HAR-conformation, and 3) brain penetration. YM976 exhibited affinity for high affinity for rolipram-conformation (HAR-conformation) (IC(50) = 2.6 nM) identical to that of rolipram (1.2 nM), and failed to show significant selectivity for the individual PDE4 subtype. These results suggested that neither subtype selectivity nor the affinity for HAR-conformation may be related to the low emetogenicity of YM976. YM976 showed a minor effect on reserpine-induced hypothermia, in contrast to rolipram. To estimate brain penetration, we then measured cAMP contents in peripheral tissues (peritoneal macrophages) and in the brain. YM976 increased the cAMP content of peritoneal macrophages, but caused no significant increase in brain cAMP levels, while rolipram elevated the cAMP content of both tissues at the same dose. In conclusion, YM976 shows an apparent dissociation between its anti-inflammatory effects and emetogenicity, perhaps because of the poor brain penetration.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed2001

[Low-dose etoposide in a patient with adult T-cell leukemia/lymphoma who had severe complications].

A 76-year-old female had been followed in our hospital for dissecting aneurysm, cardiac failure, and cerebral infarction. Inguinal lymphadenopathy, anorexia, and weight loss were noted in June 1998. The histopathologic diagnosis of the biopsied lymph node was diffuse pleomorphic type non-Hodgkin's lymphoma with T-cellular phenotype, and the patient was referred to our department. She had human T-lymphotropic virus type I seropositivity, and PCR of the pX lesion disclosed a monoclonal band. She was ultimately diagnosed as having adult T-cell leukemia/lymphoma (ATL/L, stage IV). Since she had many severe complications, she was given low-dose etoposide (LD-ETP, 50 mg/day). Atypical cells disappeared from the blood, and lymphadenopathy regressed. No major adverse reaction was observed after LD-ETP. She continued to receive intermittent LD-ETP, but she developed pneumonia in June 2000, and died in August 2000. Autopsy disclosed no residual lymphomatous lesions. These findings suggest that LD-ETP is a well tolerable and effective treatment in patients with ATL/L even if there are severe complications.

Aged↗
PubMed2001

[Early diagnosis and therapy of deep venous thrombosis with 111 indium labeled platelets].

Clinical assessment of platelet scintigraphy by using autologous platelet labeled with 111-indium oxine to detect thrombotic activity for deep vein thrombosis. Platelet accumulation on scintigrams had a tendency to correlate with aggravation of acute thrombotic symptoms in deep vein thrombosis. This method was a useful procedure to make early diagnosis of deep vein thrombosis by detecting of abnormal accumulation of platelet. In addition, appropriate thrombolytic and anticoagulant therapy resulted in reduced platelet accumulation in conjunction with improvement of acute clinical symptoms. Thus, platelet scintigraphy could be available to evaluate thrombotic activity and might be useful for determining the optimal indications of thrombolytic and anticoagulation therapies for acute deep vein thrombosis. On the other hand, another kind of scintigraphy might be inevitable especially for detection of the pulmonary embolism. Anticoagulation therapy is also effective for pulmonary embolism.

Adult↗
PubMed2001

[Calcium intake and bone mass].

The deficiency of calcium intake during childhood blocks the attainment of normal peak bone mass. On the other hand, oral calcium supplement is effective for suppressing bone loss in postmenopausal women. This effect is prominent especially in older women as well as women with lower calcium intake, and in cortical bone, compared with cancellous bone. Thus, the deficiency of calcium intake is considered to be one of major risk factors for osteoporosis, but no clear evidence have been available in Japan.

English Abstract↗
PubMed2000

CYP4B1 is a possible risk factor for bladder cancer in humans.

In experimental animals such as rats and rabbits, CYP4B1 has an important role in mutagenic activation of procarcinogens in bladders. In human bladders, it is not clear whether CYP4B1 has such role or not. In the present study, human bladder microsomes activated 2-aminofluorene which is a typical substrate for CYP4B1 and is a bladder carcinogen. CYP4B1 was detected in the human bladder microsomes by immunoblotting. Furthermore, we developed a microassay for CYP4B1 mRNA by performing real-time RT-PCR. Using this method, CYP4B1 mRNA levels were assayed in transurethal resection samples from the bladders of patients with bladder tumors. The bladder-tumor patients had a significantly higher expression of CYP4B1 than the nonbladder tumor patients. These findings suggest that a high expression of CYP4B1 increases the risk of bladder tumor by activation of carcinogenic aromatic amines. This approach could be an important tool in the assessment of human bladder cancer risk.

Adult↗
PubMed2000

A new assay for lipiodol in a tumor using a combination of m-chloroperbenzoic acid-mediated oxidation and the iodo-starch reaction.

Lipiodol, an iodine adduct lipid, has been used as a targeting carrier of anticancer drugs in experimental animals and humans. In most studies, the concentrations of the anticancer drugs in tissues and organs have been monitored, but not of the carrier because a simple method for measuring lipiodol in biological organs did not exist. Here we present an analytical method for the quantitative determination of lipiodol in tissue. This method is based on the measurement of iodine released from lipiodol by an oxidative reaction. The released iodine was measured spectrophotometrically by monitoring the iodo-starch reaction. Using this method, we were able to demonstrate the tumor specificity of lipiodol using rabbits bearing VX2 tumors in the liver. The present method is also expected to be applicable to human cancers, such as hepatic and colon cancer.

Animals↗
PubMed2000

Distribution of nociceptin/orphanin FQ precursor protein and receptor in brain and spinal cord: a study using in situ hybridization and X-gal histochemistry in receptor-deficient mice.

Nociceptin/orphanin FQ (N/OFQ) is an opioid-like heptadecapeptide agonist for the opioid receptor homolog, N/OFQ receptor. To explore the precise distribution of the peptide-receptor system, the authors examined the brain and spinal cord from receptor-deficient mice bearing the targeted mutation (morc(m1)), a lacZ insertional mutation in the N/OFQ receptor gene. Precursor protein N/OFQ (preproN/OFQ) mRNA was detected by using in situ hybridization, and the N/OFQ receptor was detected by using X-gal histochemistry. The N/OFQ receptor reflected by lacZ expression was observed at high levels in the dentate gyrus, lateral septum, subparafascicular thalamic nucleus, medial preoptic area, median preoptic nucleus, ventromedial preoptic nucleus, anterior hypothalamic area, paraventricular hypothalamic nucleus, ventromedial hypothalamic nucleus, auditory brainstem nuclei, pontine dorsal tegmentum, and nucleus of the solitary tract. In situ detection of the N/OFQ receptor mRNA by digoxigenin-labeled riboprobes coupled with tyramide signal amplification in normal and wild-type mice resulted in the regional distribution paralleling the lacZ expression in these regions. PreproN/OFQ mRNA was expressed at high levels in the subparafascicular thalamic nucleus, central gray, central tegmental field, auditory brainstem nuclei, caudal spinal trigeminal nucleus, and spinal dorsal horn. Furthermore, variable levels of expression of the peptide and receptor were seen in distinct sites of the brain and spinal cord. These data indicate a correspondence of the peptide and the receptor in local distribution at limbic, hypothalamic, and brainstem sites. Together with concurrent physiologic and behavioral studies in mutant mice, the results suggest functional roles for the N/OFQ system, including the central regulation of learning and memory, hearing ability, water balance, food intake, and blood pressure.

Animals↗
PubMed2000

1:1 complexes of dimethylthio- and ethylenedithio-tetrathiafulvalenothioquinone-1,3-dithiolemethides with CuBr2 as a new type of pi/d molecular system.

The reaction of dimethylthio- (1) and ethylenedithio-tetrathiafulvalenothioquinone-1,3-dithiolemethides (2) with CuBr2 gave 1:1 complexes between the donors and CuBr2, 1.CuBr2 and 2.CuBr2, in which the Cu atom of CuBr2 binds to the thiocarbonyl S atom in 1 and 2. The electrical conductivity (sigma) of 1.CuBr2 at room temperature was ca. 10(-5) S cm-1, while a comparatively high value of 4.0 S cm-1 was obtained for 2.CuBr2, whose temperature dependence of sigma exhibited, however, semiconducting behavior with a very small activation energy of 0.18 eV. The observed paramagnetic susceptibilities (chi p's) of the Cu complexes were composed of both a component due to the localized Cu spins obeying the Curie-Weiss law and a temperature-independent chi p due to the conducting pi electrons on the 1- or 2-stacked columns. From the Curie constants obtained, the degrees of intramolecular electron transfer from 1 and 2 to CuBr2 moieties were estimated at ca. 90% and 60%, respectively. The small, negative Weiss temperature suggest very weak antiferromagnetic interactions among the Cu spins on the CuBr2 moieties.

Journal Article↗
PubMed2000

Two novel mutations in the adrenoleukodystrophy gene in two unrelated Japanese families and the long-term effect of bone marrow transplantation.

We identified two novel missense mutations in exon 1 of adrenoleukodystrophy (ALD) gene in two unrelated Japanese families. The first, G(874)C transition results in Arg(163)Pro substitution in the cytoplasmic domain of the ALD protein in adrenomyeloneuropathy family. The second, C(679)G results in Ser(98)Trp substitution in the first transmembrane loop in childhood onset cerebral ALD family. Both mutations cause the substitution of polar amino acid (arginine and serine) with non-polar amino acid (proline and tryptophan). Bone marrow transplantation (BMT) from his non-affected his younger sister was performed on a boy with childhood onset cerebral ALD who showed neurological deficit and brain MRI abnormalities. We evaluated the effect of BMT over a 6-year period in terms of neurological deficit, the level of very-long-chain fatty acids (VLCFA) in plasma and fibroblasts, and brain MRI. After BMT, patient's peripheral white blood cells were replaced by donor's XX ones carrying a normal ALD gene confirmed by in situ hybridization using satellite DNA of the centromere of X and Y chromosomes as probes and the level of VLCFA in lymphocytes was within normal limit. However, his neurological state progressively deteriorated. BMT was not beneficial to him.

Adrenoleukodystrophy↗
PubMed2000

Evidence that atypical vasopressin V(2) receptor in inner medulla of kidney is V(1B) receptor.

Vasopressin V(2) receptors at high-density and V(1B) receptors are candidates for the V(2)-like receptor, which evokes an increase in [Ca(2+)](i) when stimulated by the vasopressin V(2) receptor agonist 1-desamino-8-D-arginine vasopressin (dDAVP) in kidney inner medullary collecting duct. We compared the pharmacological characteristics of vasopressin V(2) and V(1B) receptors in Chinese hamster ovary (CHO) cells to those of vasopressin V(2)-like receptors in rat inner medullary collecting duct cells. The vasopressin V(1B) receptor-selective agonist [deamino-Cys(1), D-3-(Pyridyl)-Ala(2), Arg(8)]vasopressin (D3PVP) did not stimulate the [Ca(2+)](i) increase in high-density vasopressin V(2) receptor-expressing CHO cells, but did in inner medullary collecting duct cells. Moreover, the vasopressin V(1A)/V(2) receptor dual antagonist 4'-[(2-methyl-1,4,5,6-tetrahydroimidazo[4,5-d][1] benzazepin-6-yl)carbonyl] 2-phenylbenzanilide (YM087), which has no effect on vasopressin V(1B) receptors, did not block the [Ca(2+)](i) increase in inner medullary collecting duct cells when stimulated by dDAVP and D3PVP. On reverse transcription-polymerase chain reaction (RT-PCR) analysis of kidney, vasopressin V(1B) receptor mRNA was detected only in the medulla. We propose that the true nature of the vasopressin V(2)-like receptor in the inner medullary collecting duct is the vasopressin V(1B) receptor, rather than the vasopressin V(2) receptor expressed at high-density.

Animals↗
PubMed2000

The molecular characterization and tissue distribution of the human cysteinyl leukotriene CysLT(2) receptor.

Cysteinyl leukotrienes (CysLTs), slow-reacting substances of anaphylaxis, are lipid mediators known to possess potent proinflammatory action. Pharmacological studies using CysLTs indicate that at least two classes of G protein-coupled receptors (GPCRs), named CysLT(1) and CysLT(2), exist; the former is sensitive and the latter is resistant to the CysLT(1) antagonists currently used to treat asthma. Although the CysLT(1) receptor gene has been recently cloned, the molecular identity of the CysLT(2) receptor has remained elusive. Here we show that the pharmacological profile of an orphan GPCR (PSEC0146) is consistent with that of the CysLT(2) receptor. In human embryonic kidney 293 cells that express the PSEC0146 cDNA, leukotriene C(4) (LTC(4)) and leukotriene D(4) (LTD(4)) induce equal increases in intracellular calcium mobilization; these increases are not affected by CysLT(1) antagonists. Additionally, [(3)H]LTC(4) specifically binds to membranes from COS-1 cells transiently transfected with PSEC0146. Large amounts of the PSEC0146 mRNA are found in human heart, placenta, spleen, and peripheral blood leukocytes but not in the lung and the trachea. Pharmacological feature and expression studies will eventually lead to a better understanding of the classification of CysLT receptors, possibly leading to a reconsideration of the pathological and physiological role of CysLTs.

Animals↗