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Biomedical subjects

T Mochizuki

Publications and source records attributed to T Mochizuki.

At least 73 records · Page 4Linked to original sources

Fas/Fas ligand expression and characteristics of primed CD45RO+ T cells in the inflamed mucosa of ulcerative colitis.

BACKGROUND: Chronic immune activation in the colon is characteristic of ulcerative colitis (UC). Fas/Fas ligand (FasL) system is a mechanism responsible for activation-induced cell death (AICD), which maintains homeostasis within the immune system. Thus, Fas/FasL expression on activated colonic T cells of UC patients, as well as the susceptibility of such T cells to AICD was investigated in order to determine the role of activated colonic T cells in the long lasting inflammation in UC. METHODS: Fas, FasL, and CD45RO expression on peripheral blood and colonic T cells of UC patients were assayed by flow cytometry. Apoptosis of colonic T cells induced by anti Fas antibody was assessed using the terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end-labeling (TUNEL) assay. RESULTS: The majority of colonic T cells expressed both CD45RO and Fas in the colonic mucosa, a situation that was quite different from that in the peripheral blood. The number of CD45RO+CD8+ and Fas+CD8+ T cells was significantly lower in UC patients than the controls, unlike the number of Fas+CD4+ T cells. In contrast, the number of both CD45RO+CD4+ and CD45RO+CD8+ T cells in UC mucosa expressing FasL was significantly higher than in the controls. While Fas mediated apoptosis of CD45RO+CD8+ T cells was higher in UC patients than the controls, the number of apoptotic CD45RO+CD4+ T cells from UC mucosa was not. CONCLUSIONS: In UC patients, CD45RO+CD4+ T cells are less sensitive to apoptotic signals mediated by Fas. These phenomena may contribute to the pathogenesis of UC.

Adult↗

Two cases of pediatric bone disease (eosinophilic granuloma and Brodie's abscess) showing similar scintigraphic and radiographic findings.

Two 9-year-old patients with femoral bone lesions were referred to the authors' institution within a few days of each other. Both showed similar radiographic, magnetic resonance imaging, and scintigraphic findings. The radiographs showed osteolytic lesions in the right femoral diaphyses, and gadolinium-DTPA-enhanced magnetic resonance imaging revealed inhomogeneous enhancement. Tc-99m HMDP showed marked linear accumulation with relatively low central uptake in the right femoral shafts, and TI-201 scintigraphy showed considerable uptake corresponding to the area seen with Tc-99m HMDP. Histologic analysis confirmed eosinophilic granuloma in the first patient and Brodie's abscess in the second. The radiographic and scintigraphic findings in Brodie's abscess may be similar to those in eosinophilic granuloma.

Child↗

Tc-99m PMT hepatobiliary scintigraphy in the differential diagnosis of extrahepatic metastases and hepatocellular carcinoma.

PURPOSE: The authors evaluated the utility of hepatobiliary scintigraphy for tissue characterization of extrahepatic metastases from hepatocellular carcinoma (HCC) using Tc-99m N-pyrydoxyl-5-methyltriptophane (Tc-99m PMT). METHODS: We examined 13 patients with HCC (29 extrahepatic metastases and 3 benign bone lesions) and 5 patients with other cancers (15 extrahepatic metastases). Thirty minutes to 6 hours after intravenous administration of Tc-99m PMT, planar (all 47 lesions) and SPECT (42 lesions) images were obtained. Accumulation of Tc-99m PMT in the lesion was evaluated visually by comparing bone scintigraphy, computed tomography, magnetic resonance imaging, or all of these. RESULTS: Findings were positive in 12 of 13 patients with HCC and extrahepatic metastases (16 of 29 on planar imaging and 21 of 26 on SPECT). Findings in all three benign bone lesions and 15 metastatic lesions from non-HCC primary lesions were negative (0 of 18 on planar imaging, 0 of 16 on SPECT). There were no false-positive findings in these lesions. Lesion-by-lesion sensitivity, specificity, accuracy, and positive and negative predictive values were 55%, 100%, 72%, 100%, and 58% by planar imaging and 81%, 100%, 88%, 100%, and 76% by SPECT, respectively. CONCLUSIONS: Because of the high specificity and reasonable sensitivity, Tc-99m PMT appears to be useful for the differential diagnosis of extrahepatic metastases from HCC. SPECT improves the detectability of small or faint accumulation in metastases from HCC.

Aged↗

Inverted papilloma arising in a juvenile.

A 15-year-old man presented with painless, gross hematuria. Excretory pyelography showed a filling defect in the bladder and ultrasonography revealed a solitary bladder tumor. Cystoscopy showed a solitary, papillary tumor on the bladder neck. Transurethral resection was then performed and histological examination showed an inverted papilloma. In addition, the expression of proliferative cellular nuclear antigen and p53 in the surgical specimen were 37.1 and 0%, respectively. Since an inverted papilloma arising during the first two decades of life is quite rare, we herein report the above case and review previous reports.

Adolescent↗

Improvement in fatty acid utilization in relation to a change in left ventricular hypertrophy in spontaneously hypertensive rats.

Although fatty acid metabolism is reportedly impaired in myocardial hypertrophy, it is unclear whether the antihypertensive drugs are associated with improved fatty acid metabolism. In order to evaluate the effects of antihypertensive drugs on fatty acid metabolism and myocardial perfusion, the simultaneous uptake of iodine-125(125I)-15-(p-iodophenyl)-3-(R,S)-methylpentadecanoic acid (BMIPP) and thallium-201 (Tl) were measured in 3 groups of rats: (1) spontaneously hypertensive rats (SHR) without treatment (SHR-N), (2) SHR chronically treated with captopril (SHR-C), and (3) SHR chronically treated with hydralazine (SHR-H). Captopril and hydralazine were administered to their respective groups for 3 weeks from 12 weeks of age. The hearts were removed 10 min after simultaneous intravenous injections of BMIPP and Tl and the 125I and 201Tl counts were measured to calculate the uptake ratio. The systolic blood pressure (SBP) in SHR-N was 222+/-10 mm Hg, whereas the SHR-C and SHR-H groups showed significant SBP reduction (156+/-11, and 158+/-10 mm Hg, respectively) (p<0.01 each). The heart/bodyweight ratio was significantly lower in SHR-C (2.48+/-0.09) than in SHR-N (2.74+/-0.11) (p<0.05). However, there was no significant difference in the heart/bodyweight ratio between SHR-N and SHR-H (2.65+/-0.09). The ratio of BMIPP uptake to Tl uptake (BMIPP/Tl) was significantly higher in SHR-C (0.71+/-0.13) than in SHR-N (0.50+/-0.09) (p<0.05). However, BMIPP/Tl in SHR-H (0.53+/-0.09) was similar to that in SHR-N. These results suggest that captopril improves fatty acid metabolism in the hypertrophied ventricle in SHR. The metabolic alterations may improve with left ventricular hypertrophy regression but are not effected by the reduction of blood pressure only.

Angiotensin-Converting Enzyme Inhibitors↗

Two- and three-dimensional CT ventriculography: a new application of helical CT.

OBJECTIVE: We propose a new application of helical CT, CT ventriculography, which can produce two-dimensional (2D) and three-dimensional (3D) images of different cardiac phases (plus animation). We sought to determine the accuracy of CT ventriculography for assessing left ventricular volumes. MATERIALS AND METHODS: With a single breath-hold, the patient's entire heart was scanned with an ECG-gating technique (3-mm-thick collimation, 2 mm per rotation table speed, 0.8 sec per rotation, and 50 rotations through 10 cm in total). Using a 0.2-mm (0.08-sec) interval (10 slices per rotation) overlapping reconstruction, about 500 axial slices were obtained and reordered to separate different cardiac cycles. Then, 2D cardiac axes and 3D images were reconstructed and animated movies of the 2D and 3D images were produced. In 21 patients, the left ventricular end-diastolic volume, end-systolic volume, and ejection fraction were assessed and compared with left ventriculography. Correlations and agreements between CT and left ventriculography were determined. RESULTS: Close correlations between CT and left ventriculography were obtained (r = 0.95, 0.98, and 0.91, for end-diastolic volume, end-systolic volume, and left ventricular ejection fraction, respectively; p < 0.0001 for all values). The limits of agreement between CT and left ventriculography were 44.3 to -44.5 ml for end-diastolic volume, 19.8 to -29.0 ml for end-systolic volume, and 19.7% to -9.5% for left ventricular ejection fraction. CONCLUSION: This cardiac application of helical CT provides a clear morphology along the cardiac axes and 3D images and an assessment of left ventricular volumes (end-diastolic volume, end-systolic volume, and left ventricular ejection fraction).

Adult↗

Two cases of tinea corporis by infection from a rabbit with Arthroderma benhamiae.

The first cases of tinea corporis with Arthroderma benhamiae in Japan are reported. A 7-year-old girl and a 30-year-old mother in Shimane prefecture suffered from dermatophyte infections on the neck, shoulder, arms and leg. Three isolates from the two patients and a rabbit by which they supposedly were infected, were identified as Trichophyton mentagrophytes. On the bases of mating tests using the tester strains of both the African race and the Americano-European race of A. benhamiae, they were identified as A. benhamiae African race mating type (-). Our results are the first to indicate that both races of A. benhamiae exist in Japan.

Adult↗

[Phaeomycotic cyst caused by Phaeoacremonium parasiticum].

Phaeoacremonium parasiticum was identified as the causative agent of a phaeomycotic cyst seen just below the right knee of a 59-year-old healthy woman. She had no history of trauma. Direct KOH examination of the pus aspirated from the subcutaneous nodule revealed abundant mycelia, which were not too deeply brown in color. The nodule was surgically excised, and there was no recurrence during a half year of observation. Tissue section of the excised material revealed rather a large cavity extending from the cutis to the subcutis. The cavity had a thick wall composed of granulomatous tissues. Mycelial and yeast-like fungal elements were seen within the cavity and the granulomatous tissues. A dematiaceous fungus was cultured from both pus and the excised material. The isolates were characterized by a dark green to black colony, unbranched or infrequently branched, brownish conidiophores bearing an aculeate monophialide with a narrow funnel-shaped collarette, and slimy, hyaline, one-celled, ellipsoid to allantoid conidia.

Cysts↗

[Usefulness of the low protein rice on the diet therapy in patients with chronic renal failure].

Diet therapy for patients with chronic renal failure is based on low protein and high energy. To achieve strict diet therapy, it is necessary to use specially formulated low protein foods. Previously, rice with a low content of protein was not available, but recently, a low protein rice (LGC-1: low glutelin content-1) has been developed. LGC-1 was found to have a low content of glutelin in its seed protein compared to other ordinary rice. Glutelin is the major digestive protein in the rice grain. We studied the usefulness of LGC-1 in the diet therapy of patients with chronic renal failure. Twenty-three patients were placed on the low protein diet (0.6-0.9 g/kg/day) during the pre-study period (a mean of 10 months). Subsequently they were followed with the same diet using LGC-1 for the staple foods during the study period (mean of 7 months). Protein intake and the slope of the reciprocal of serum creatinine did not differ between each study period in all patients. Among the 23 patients, 9 consumed rice mainly as the staple food (120-180 g/day as polished rice: rice group), according to the results of a questionnaire. In the rice group, protein intake decreased (from 47 +/- 9 to 42 +/- 9 g/day, p < 0.05), and the slope of the reciprocal of serum creatinine reduced (from -4.59 +/- 4.33 to -1.47 +/- 3.51 x 10(-4) dl/mg/day, p < 0.05) during the study period, compared with the pre-study period. We conclude that LGC-1 is a useful and effective food for a low protein diet in patients with chronic renal failure, especially, for those who consume rice mainly as their staple food.

Aged↗

[Immunohistochemical analysis of the normal and cystic kidney using antibody against polycystin 2].

A second gene responsible for polycystic kidney disease(PKD) has been identified recently, and an antisera(YCC2) against this gene's product, polycystin 2, has been generated. In the present study, we investigated the normal distribution of polycystin 2 in human adult kidneys and analyzed the expression of polycystin 2 in the cystic tubules of kidneys from patients with PKD and acquired cystic disease of the kidney(ACDK). The expression of polycystin 2 in normal regions of resected human kidneys, 4 cases of autosomal dominant polycystic kidney disease(ADPKD) and 4 cases of ACDK was examined by immunohistochemically staining the specimens with a polyclonal antibody specific to the C-terminal region of polycystin 2. This region is specific to polycystin 2 and does not crossreact with polycystin 1. In normal kidneys, prominent expression of polycystin 2 was observed in the distal tubules. A faint level of expression was detected in the proximal tubules, and the glomerulus and vessels were almost negative for expression. In the cystic kidneys of ADPKD patients, 68.7% of the cystic tubules stained positively for YCC2, although partial staining was seen in 41.2% of the positive cystic tubules. Although the genetic background of the samples is unknown, the co-existence of positive and negative cysts suggest that a "two-hit" hypothesis is feasible and that the mutations are likely to be missense or in frame changes. In ACDK cysts, YCC2-positive staining was prominent in small cysts (less than 0.5 mm in diameter), which were also positive for DBA, a marker for distal tubules. In contrast, larger cysts of more than 0.5 mm in diameter which stained positive for a proximal tubule marker, Lotus T, tended to be less positively stained for YCC2. Overall, 94.5% of the cysts stained positive for YCC2, which is a much higher rate than that of PKD cysts. These results suggest that ACDK cysts may be generated by a different mechanism from that of PKD cysts.

Humans↗

Regulation of c-Myc through phosphorylation at Ser-62 and Ser-71 by c-Jun N-terminal kinase.

The expression of c-myc promotes cell proliferation and also sensitizes cells to various extracellular apoptotic stimuli. However, signal pathways regulating the function of Myc proteins during apoptosis are unknown. c-Jun N-terminal kinase (JNK) is activated by various apoptotic stimuli, but neither the target molecule(s) or the action of JNK has been identified in Myc-mediated apoptosis. Here, we found that JNK selectively interacted with, and phosphorylated, c-Myc at Ser-62 and Ser-71 as confirmed with phospho-c-Myc-specific antibodies. Interestingly, dominant negative mutant JNK(APF) impaired the c-Myc-dependent apoptosis, but not mutated c-Myc (S62A/S71A)-dependent apoptosis triggered by UV irradiation. Furthermore, c-Myc (S62A/S71A)-expressing NIH3T3 cells were not sensitized like wild type c-Myc-expressing NIH3T3 cells to JNK-activating apoptotic stimuli, such as UV and Taxol. These results indicate that the JNK pathway is selectively involved in the c-Myc-mediated apoptosis and that the apoptotic function of c-Myc is directly regulated by JNK pathway through phosphorylation at Ser-62 and Ser-71.

3T3 Cells↗

Toward the best treatment for uncomplicated patients with type B acute aortic dissection: A consideration for sound surgical indication.

BACKGROUND: In the treatment of type B acute aortic dissection without complications, better results are obtained if surgery is performed before enlargement of the aorta in patients who are predicted to show aortic enlargement and if drug-based treatment is continued for patients who are predicted to show no enlargement. The purpose of this study was to predict the acute-phase factors that may affect chronic-phase aortic enlargement by studying chronic-phase enlargement of dissections in patients without complications during the acute phase. METHODS AND RESULTS: In 101 patients with type B acute dissection who had no complications, univariate and multivariate factor analyses were performed to determine the predictors for chronic-phase enlargement (>/=60 mm) of the dissected aorta. The independent predominant predictors for aortic enlargement in the chronic phase were a maximum aortic diameter of >/=40 mm and a patent false lumen during the acute phase. The values of actuarial freedom from aortic enlargement for the patients with a maximum aortic diameter of 40 mm and a patent false lumen at 1, 5, and 10 years were 43%, 33%, and 22%, respectively, whereas in patients with a maximum aortic diameter of <40 mm and a closed false lumen, the values were 97%, 94%, and 84%, respectively. CONCLUSIONS: These results suggest that patients with type B acute aortic dissection who show a maximum aortic diameter of >/=40 mm and a patent false lumen should undergo surgery earlier during the chronic phase before enlargement of aorta, whereas patients with a maximum aortic diameter of <40 mm and a closed false lumen should continue to receive hypotensive therapy.

Adult↗

Identification and characterization of polycystin-2, the PKD2 gene product.

PKD2, the second gene for the autosomal dominant polycystic kidney disease (ADPKD), encodes a protein, polycystin-2, with predicted structural similarity to cation channel subunits. However, the function of polycystin-2 remains unknown. We used polyclonal antisera specific for the intracellular NH(2) and COOH termini to identify polycystin-2 as an approximately 110-kDa integral membrane glycoprotein. Polycystin-2 from both native tissues and cells in culture is sensitive to Endo H suggesting the continued presence of high-mannose oligosaccharides typical of pre-middle Golgi proteins. Immunofluorescent cell staining of polycystin-2 shows a pattern consistent with localization in the endoplasmic reticulum. This finding is confirmed by co-localization with protein-disulfide isomerase as determined by double indirect immunofluorescence and co-distribution with calnexin in subcellular fractionation studies. Polycystin-2 translation products truncated at or after Gly(821) retain their exclusive endoplasmic reticulum localization while products truncated at or before Glu(787) additionally traffic to the plasma membrane. Truncation mutants that traffic to the plasma membrane acquire Endo H resistance and can be biotinylated on the cell surface in intact cells. The 34-amino acid region Glu(787)-Ser(820), containing two putative phosphorylation sites, is responsible for the exclusive endoplasmic reticulum localization of polycystin-2 and is the site of specific interaction with an as yet unidentified protein binding partner for polycystin-2. The localization of full-length polycystin-2 to intracellular membranes raises the possibility that the PKD2 gene product is a subunit of intracellular channel complexes.

Amino Acid Sequence↗

Activation of sensory nerves participates in stress-induced histamine release from mast cells in rats.

To elucidate the mechanism by which stress induces rapid histamine release from mast cells, Wistar rats, pretreated as neonates with capsaicin, were subjected to immobilization stress for 2 h, and histamine release was measured in paws of anesthetized rats by using in vivo microdialysis after activation of sensory nerves by electrical or chemical stimulation. Immobilization stress studies indicated that in control rats stress induced a 2.7-fold increase in the level of plasma histamine compared to that in freely moving rats. Whereas pretreatment with capsaicin significantly decreased stress-induced elevation of plasma histamine. Microdialysis studies showed that electrical stimulation of the sciatic nerve resulted in a 4-fold increase of histamine release in rat paws. However, this increase was significantly inhibited in rats pretreated with capsaicin. Furthermore, injection of capsaicin into rat paw significantly increased histamine release in a dose-dependent manner. These results suggest that activation of sensory nerves participates in stress-induced histamine release from mast cells.

Animals↗

Evidence for direct binding of fatty acids and eicosanoids to human peroxisome proliferators-activated receptor alpha.

The alpha isoform of peroxisome proliferators-activated receptor (PPAR) is activated by fatty acids, their metabolites, and the fibrate class of lipid-lowering agents. To test the ability of these activators to directly bind the ligand-binding domain of human PPARalpha, we performed a competitive binding assay using radiolabeled [(3)H]KRP-297, a known ligand for human PPARalpha. Long-chain fatty acids and eicosanoids were even more potent ligands for human PPARalpha than the hitherto most potent PPARalpha ligand WY-14,643. Moreover, these natural ligands avidly activated this receptor in a transient transcriptional assay. This study provides the direct evidence that human PPARalpha is activated through the direct binding of fatty acids and eicosanoids, as well as of a fibrate, to its ligand-binding domain.

Animals↗

Physical and functional interactions between Pim-1 kinase and Cdc25A phosphatase. Implications for the Pim-1-mediated activation of the c-Myc signaling pathway.

The pim-1 oncogene encodes a serine/threonine kinase (Pim-1) involved in the transduction of cytokine-triggered mitogenic signals. Pim-1 is unique in that it closely cooperates with c-Myc not only in oncogenesis, but also in apoptosis induction. However, the molecular basis of Pim-1 function remains poorly understood, largely because the downstream effector molecule(s) for Pim-1 kinase has not been identified. Here we provide several lines of evidence that Cdc25A cell cycle phosphatase, a direct transcriptional target for c-Myc, is a substrate for Pim-1 kinase and functions as an effector for Pim-1. We found that Pim-1 physically interacts with Cdc25A both in vitro and in vivo and phosphorylates Cdc25A. We also observed that Pim-1-mediated phosphorylation of Cdc25A increases its phosphatase activity. In addition, wild-type Pim-1, but not kinase-inactive Pim-1, enhanced Cdc25A-mediated cellular transformation and apoptosis. Our results indicate that Cdc25A might be a key molecule that links Pim-1 and c-Myc and that also ties Pim-1-mediated mitogenic signals to cell cycle machinery.

Animals↗