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T Higuchi

Publications and source records attributed to T Higuchi.

At least 217 records · Page 12Linked to original sources

Expression of calcium binding protein D-9k messenger RNA in the mouse uterine endometrium during implantation.

To investigate the molecular mechanisms of implantation, we constructed a cDNA library of mouse uteri enriched with pregnancy-induced genes by subtractive hybridization and polymerase chain reaction (PCR). One of the isolated clones was the cDNA for the calcium binding protein D-9k (Cabp9k), which is considered to regulate intracytoplasmic concentration and transport of free calcium ions. Northern blot and in-situ hybridization analyses demonstrated that the Cabp9k mRNA was expressed in the endometrial epithelia, both luminal and glandular, in the uterus at the time of implantation. On pregnancy day 5 it was detected in the luminal, but not in the glandular, epithelia. In the oophorectomized adult mice, progesterone enhanced Cabp9k mRNA expression in the uterus, whereas oestrogen did not. Consistent with this, a nucleotide change was identified in the first intron of mouse Cabp9k gene corresponding to the oestrogen responsive element in the rat Cabp9k gene. Transfer of embryos into the uterine cavity of pseudopregnant mice reduced the expression of Cabp9k mRNA in the glandular epithelium, suggesting that Cabp9k mRNA expression is also regulated by embryonal signal(s). These findings demonstrated that Cabp9k mRNA is expressed in the endometrial epithelia during the implantation period under the control of progesterone and the presence of embryo, and suggest that CaBP9k plays a role in implantation by regulating the local calcium concentrations.

Amino Acid Sequence↗

CD9 is expressed in extravillous trophoblasts in association with integrin alpha3 and integrin alpha5.

The CD9 molecule is a 24-27 kDa cell surface glycoprotein, which may be related to Schwann cell migration and adhesion. In this study, we examined the expression of CD9 in human extravillous trophoblasts, which invade into the endometrium during implantation and placentation. CD9 was detected immunohistochemically on the extravillous trophoblasts in the cell columns of first trimester placentae, but not on villous trophoblasts. In the second and third trimester, CD9 was highly expressed on the extravillous trophoblasts in the basal plate of placentae, and in the chorion laeve in the fetal membrane of term placentae. The molecular mass of CD9 in the chorion laeve was shown to be 27 kDa by Western blotting. The mRNA of CD9 was also detected in the chorion laeve by reverse transcription-polymerase chain reaction (RT-PCR). Proteins were purified from chorion laeve by affinity chromatography with anti-integrin alpha3 and alpha5 monoclonal antibodies and Western blotting, revealed that CD9 was associated with both integrins. These findings indicate that CD9 is a differentiation-related molecule present in the extravillous trophoblasts. Since it is associated with integrin alpha5 which has been proposed to regulate trophoblast invasion, CD9 may be implicated in trophoblast invasion at the feto-maternal interface.

Antigens, CD↗

CD9 is involved in invasion of human trophoblast-like choriocarcinoma cell line, BeWo cells.

The CD9 molecule is expressed on human extravillous trophoblasts, which invade the endometrium during implantation and placentation. To elucidate the role of CD9 in trophoblastic function, we investigated the expression of CD9 protein and mRNA in BeWo cells, a human trophoblast-like choriocarcinoma cell line, using immunohistochemistry, Western blotting and reverse transcription-polymerase chain reaction (RT-PCR). When BeWo cells were cultured with anti-CD9 monoclonal antibodies (mAb), their invasion through the extracellular matrices was significantly enhanced in a dose-dependent manner. Cell proliferation and human chorionic gonadotrophin production were unaffected. On the other hand, culture in the presence of mAb against integrins alpha3, alpha5 and beta1, which partially block the interaction with the extracellular matrices, inhibited BeWo cell invasion. Anti-CD9 monoclonal antibody had a stimulatory effect on BeWo cell invasion in the presence of anti-integrin alpha3 antibody. In contrast, it had no effect in the presence of mAb against integrins alpha5 and beta1, which were also highly expressed on BeWo cells. These findings suggest that CD9 has a function connected with the invasive properties of BeWo cells, which is partially mediated by integrin alpha5beta1. This may relate to the involvement of CD9 in trophoblastic invasion.

Antibodies, Monoclonal↗

Human granulosa cells express integrin alpha2 and collagen type IV: possible involvement of collagen type IV in granulosa cell luteinization.

Previously, it has been shown that integrin alpha6beta1 expressed on human granulosa cells regulates luteinization in co-operation with its ligand, laminin. In this study, integrin alpha2 was immunohistochemically demonstrated to be expressed on granulosa and large luteal cells. It was also detected on luteinizing theca interna cells after ovulation. Immunoreactive collagen type IV, which is one of the ligands for integrin alpha2beta1, was detected around granulosa cells in the pre-ovulatory follicles and its expression was rapidly increased during ovulation. By flow cytometry, collagen type IV was detected on the cell surface of luteinizing granulosa cells isolated from pre-ovulatory follicles, confirming the physiological interaction between granulosa cells and collagen type IV. Collagen type IV in follicular fluid was positively related with progesterone concentration. In 4-day cultures of granulosa cells, collagen type IV in the media was significantly increased by human chorionic gonadotrophin (HCG). The progesterone production was significantly attenuated when granulosa cells were cultured on collagen type IV-coated dishes, suggesting that collagen type IV suppresses granulosa cell luteinization. These findings show that collagen type IV, a ligand for integrin alpha2beta1, is rapidly produced around luteinizing granulosa cells during ovulation, probably under the control of luteinizing hormone (LH) and suggest that collagen type IV is a new parameter and/or regulator of granulosa cell luteinization in the periovulatory phases.

Antigens, CD↗

Biodistribution and scintigraphy of [111In]DTPA-adriamycin in mammary tumor-bearing rats.

The aim of this study was to develop an 111In-labeled diethylenetriamine pentaacetic acid-adriamycin (DTPA-ADR) conjugate to image breast cancer. DTPA-ADR was synthesized by reacting adriamycin with DTPA anhydride in the presence of carbonyldiimidazole. After dialysis (MW cut off was 500), the product was freeze-dried (yield 40-50%). An in vitro cell culture study was performed using cells from the 13,762 Fischer rat mammary tumor line. Drug concentrations tested were 0.1-100 microM. Biodistribution studies were conducted at 0.5, 2, 24 and 48 h in mammary tumor-bearing rats (n = 3/time interval, 10 microCi/rat, i.v.) with 13,762 cells (10(5) cells/rat, s.c.). Planar imaging and autoradiograms were obtained at the same intervals. In vitro cell culture assays showed an IC50 of 0.1 +/- 0.01 microM for ADR and 7.2 +/- 0.29 microM for DTPA-ADR, respectively. In biodistribution studies, tumor/blood uptake ratios of [111In]DTPA-ADR at 0.5, 2, 24 and 48 h were 0.55 +/- 0.17, 0.94 +/- 0.17, 3.06 +/- 0.53 and 3.66 +/- 0.35, respectively, whereas those for [111In]DTPA (control) were 1.19 +/- 0.69, 0.84 +/- 0.07, 0.56 +/- 0.10 and 0.60 +/- 0.03, respectively. The tumor uptake value (%ID/g) of [111In]DTPA-ADR at 0.5 h was 0.20 +/- 0.06. Planar images and autoradiograms showed good visability of tumors. Biodistribution, autoradiography and radionuclide imaging of [111In]DTPA-ADR in breast tumor-bearing rats showed that tumor-to-blood ratios increased steadily between 30 min and 48 h. These results indicate that DTPA-ADR, a new cancer imaging agent, might be useful in the diagnosis of breast cancer and may predict a therapeutic effect prior to treatment.

Animals↗

Metabolic studies of [18F-alpha-methyl]tyrosine in mice bearing colorectal carcinoma LS-180.

Brain and tumor uptake of [18F-alpha-methyl]tyrosine (18F-AMT) and the incorporation into each of four fractions (lipid, RNA, DNA and protein) were investigated in mice bearing LS180 colorectal carcinoma. Homogenized tissues were analyzed by the fractionation method into an acid-soluble fraction (ASF) and an acid-precipitable fraction (APF). The APF was further investigated to assess the incorporation of 18F-AMT into each fraction. Incorporation into four fractions of brain and tumor at 60 min post-injection was 20 and 12%, respectively; 10% of the activity was incorporated to lipid in brain and 5% in tumor. There was 5, 2 and 2% incorporation with RNA, DNA and protein, respectively. Metabolites in ASF were analyzed by high-performance liquid chromatography and thin-layer chromatography. There was only one radioactive peak, which corresponded to 18F-AMT. The incorporation of 18F-AMT into lipid was twice that of 18F-AMT in tumor. The uptake of 18F-AMT in tissues was rapid and accomplished before 30 min, and then slowly diffused in blood. These results implied that 18F-AMT was metabolized to protein to only a small extent and trapped as intact 18F-AMT in cells up to 60 min. We conclude that 18F-AMT is a promising tracer for tumor imaging and quantification of the transport rate using two-compartment models.

Animals↗

Magnetic resonance imaging of pseudotumors of the craniovertebral junction in long-term hemodialysis patients.

BACKGROUND/AIMS: Pseudotumors of the craniovertebral junction (PTCVJ) are observed in long-term hemodialysis (HD) patients. There are neither criteria for diagnosis nor guidelines for screening. We attempted to determine magnetic resonance imaging (MRI) findings that could be used to detect PTCVJ, to determine the prevalence of PTCVJ, and to evaluate whether destructive spondyloarthropathy (DSA) might be a yardstick for selection of patients for MRI examination for PTCVJ. METHODS: MRI were examined in 19 DSA patients (8 males, 11 females, age 61.4 +/- 7.3 years, HD duration 17.0 +/- 4.4 years) and in 20 sex-, age-, and HD-duration-matched non-DSA patients (9 males, 11 females, age 57.5 +/- 6.6 years, HD duration 17.7 +/- 4.9 years). We evaluated MRI characteristics of PTCVJ according those which occur due to rheumatoid arthritis. RESULTS: PTCVJ were characterized as follows: disappearance of fat pads in the upper region (supradental PTCVJ), intensity change of the 'predental triangle' in the anterior region (predental PTCVJ), and thickening of cruciform ligaments (retrodental PTCVJ). The prevalence of PTCVJ among patients undergoing HD more than 10 years was high (26 out of 39; 66.7%). The prevalence of PTCVJ was not different between DSA and non-DSA groups. CONCLUSION: We verified that the above MRI findings might be helpful in the detection of PTCVJ. These findings were observed frequently and independently also in patients with DSA.

Amyloidosis↗

Decreases in blood pressure and sympathetic nerve activity by microvascular decompression of the rostral ventrolateral medulla in essential hypertension.

BACKGROUND: Neurovascular compression of the rostral ventrolateral medulla, a major center regulating sympathetic nerve activity, may be causally related to essential hypertension. Microvascular decompression of the rostral ventrolateral medulla decreases elevated blood pressure. CASE DESCRIPTION: A 47-year-old male essential hypertension patient with hemifacial nerve spasms exhibited neurovascular compression of the rostral ventrolateral medulla and facial nerve. Microvascular decompression of the rostral ventrolateral medulla successfully reduced blood pressure and plasma and urine norepinephrine levels, low-frequency to high-frequency ratio obtained by power spectral analysis, and muscle sympathetic nerve activity. CONCLUSIONS: This case suggests not only that reduction in blood pressure by microvascular decompression of the rostral ventrolateral medulla may be mediated by a decrease in sympathetic nerve activity but also that neurovascular compression of this area may be a cause of blood pressure elevation via increased sympathetic nerve activity.

Blood Pressure↗

Dipeptides containing L-arginine analogs: new isozyme-selective inhibitors of nitric oxide synthase.

Several L-arginine analogs are known as potent inhibitors of nitric oxide synthase (NOS). We recently synthesized dipeptides containing such amino acids, and found that they are potent and isozyme-selective NOS inhibitors. For example, S-methyl-L-isothiocitrullinyl-L-phenylalanine showed 66-fold selectivity for iNOS over nNOS, while S-methyl-L-isothiocitrullinyl-L-leucine and N(G)-nitro-L-argininyl-L-phenylalanine showed 20- and 14-fold selectivity, respectively. Interestingly, S-methyl-L-isothiocitrullinyl-D-phenylalanine showed no selectivity, and S-methyl-L-isothiocitrullinyl-L-phenylalanine showed competitive inhibition. These results suggest that each NOS isozyme has a cavity of different size near the C-terminal of the L-arginine binding site, and that the selectivity of inhibitors is due to the differences in the size of the cavity.

Animals↗

Bone regeneration by recombinant human bone morphogenetic protein-2 in rat mandibular defects. An experimental model of defect filling.

BACKGROUND: Bone defects and irregularities are major problems for dental implant and periodontal therapies. METHODS: We investigated whether the application of recombinant human bone morphogenetic protein-2 (rhBMP-2) induces bone formation in through-and-through bone defects in the rat mandible. A round through-and-through bone defect (5 mm in diameter) was created in the angle of the mandible on both sides of the jaw using a steel round bur in each of 8 Long-Evans rats. In the experimental group, polylactic acid-polyglycolic acid copolymer/gelatin sponge (PGS) containing rhBMP-2 (6 microg/60 microl) was inserted in the bone defect. In the control group, the same carrier without rhBMP-2 was applied in the bone defect on the opposite side. Four weeks after application, the rats were sacrificed. Step serial sections stained with hematoxylin and eosin at intervals of 200 microm were prepared in a bucco-lingual direction. The size of the bone defects and new bone formation were evaluated histometrically. RESULTS: In all cases in the experimental group, a large quantity of newly formed bone was observed. The bone defects were completely filled with new bone in 4 of 8 rats in the experimental group. In the control group, small amounts of new bone formation were observed along the border of the original mandibular bone. Histometrical analysis revealed that the amount of new bone was significantly larger in the rhBMP-2 treated sites than in the control sites (P <0.0001; paired t-test). CONCLUSIONS: These results indicate that the rhBMP-2/PGS system induced effective bone regeneration on mandibular defects in rats. This procedure may be suitable as an experimental model for bone regeneration using various growth factors and effective for alveolar ridge augmentation followed by dental implant surgery.

Animals↗

MR imaging of endometrial stromal sarcoma: correlation with pathologic findings.

OBJECTIVE: This study describes MR imaging of eight patients with endometrial stromal sarcoma and correlates the imaging findings with histopathologic findings. To our knowledge, the radiologic findings of this entity have not been reported in the literature. CONCLUSION: Endometrial stromal sarcoma typically presents with extensive myometrial involvement, which is either sharply demarcated or diffusely infiltrative. Bands of low signal intensity are observed within the areas of myometrial involvement on T2-weighted images. These bands correspond to the preserved bundles of myometrium on pathologic examination. Tumor extension along the vessels or ligaments is another characteristic of MR imaging of endometrial stromal sarcoma.

Adult↗

Transition of polycythemia vera to chronic neutrophilic leukemia.

Two cases of polycythemia vera (PV) had transition to a hematological condition compatible with chronic neutrophilic leukemia (CNL) 17 and 8 years after diagnosis, respectively. One patient was treated with carboquone followed by hydroxyurea (HU) and the other with HU during PV phase. On transition, both had neutrophilia with white blood cell count above 40,000/microl, elevated neutrophil alkaline phosphatase activity, splenomegaly, normal karyotype without bcr-abl rearrangement. Busulfan was temporally effective in controlling the neutrophil count. However, one patient progressed to the so-called spent phase and the other subsequently had multiple transitions between PV and CNL. These cases may represent a form of uncommon evolution of PV and support the contention that CNL is a type of myeloproliferative disorder and that at least some CNL cases have derangement at the hematopoietic stem cell level.

Busulfan↗

[Assessment of ECG-gated myocardial SPECT analysis program with cardiac phantom and clinical data].

PURPOSES: ECG-gated myocardial SPECT program (QGS) is coming into wide use. This program permits measurement of end-diastolic volume (EDV), and end-systolic volume (ESV) and ejection fraction (EF) by automatic detection of myocardial edges. We assessed the reproducibility, accuracy, factors that affect the measurement of these indices using a cardiac phantom and clinical data. METHODS: In the phantom study, we evaluated the effects of ventricular volume, location, absorption, acquisition time, enlarged acquisition and pre-filter on the calculated indices. In the clinical study using 99mTc-MIBI, reproducibility between 2 observers, comparison with left ventriculography and effects of pre-filter were assessed. In clinical cases of 201TI and 123I-BMIPP, left ventricular volume and EF were also analyzed by QGS with various pre-filters. RESULTS: Although the true phantom volumes (y) and calculated volumes (x) showed an excellent linear correlation (y = 0.94x - 13.8, r = 0.999), calculated volumes were significantly under-estimated by 14.5-33.8%. An absorbent material around the phantom caused reduction in calculated volumes by 4.1-9.1%. Duration of acquisition times, 3 to 60 seconds per projection, did not influence the calculation of the parameters. With enlarged data collection, calculated volume (37 ml) was larger than that of normal acquisition (33 ml). When the cut-off frequency of Butterworth filter was changed, these indices of volume and EF were almost stable over 0.41 cycle/cm. There was an excellent correlation in intra-observer measurements for EDV (r = 0.998, p < 0.0001), ESV (r = 0.998, p < 0.0001) and EF (r = 0.995, p < 0.0001). In comparison with left ventriculography, correlation of parameters was good in ESV (r = 0.91, p < 0.0001), EF (r = 0.88, p < 0.0001), but was fair in EDV (r = 0.78, p < 0.0001). The QGS program underestimated EDV, ESV and EF. CONCLUSION: QGS program with gated SPECT is useful to calculate relative volume and EF. However, to calculate absolute values, we should understand the various factors that affect the result of QGS.

Aged↗

[Assessment of regional myocardial function by ECG-gated myocardial SPECT].

PURPOSES: Regional myocardial functional parameters were assessed by ECG-gated myocardial SPECT analysis in normal subjects and ischemic heart diseases. METHODS: Normal subjects (13 male and 10 female) and 51 patients with chronic ischemic heart disease underwent ECG-gated myocardial SPECT. A dose of 740 MBq of 99mTc-MIBI was injected at rest, and gated SPECT was performed 60 min later. Wall motion (WM) and systolic wall thickening (WT), % tracer uptake were evaluated by quantitative gated SPECT program (QGS). Regional parameters were obtained in the 16 segments based on the functional polar map. In the normal group, standard values were evaluated in the lateral, septal, anterior and inferior regions both in male and female subjects. In the ischemic heart disease group, sensitivity and specificity of these parameters were assessed in each segment. To estimate the ability of WM and WT in detecting regional dysfunction, decreased perfusion area, which was defined as < mean - 2SD by the normal profile, was used as a standard. The receiver operating characteristics (ROC) area analysis was also performed. RESULT: In the normal profile, % tracer uptake was decreased in the anterior segments of female group, no significant difference was observed between male and female in WM and WT. WM was decreased in the septum and increased in the lateral segment. WT didn't show any difference regional difference. Sensitivity and specificity of WM were 56%/91% in the anterior, 0%/100% in the septum, 43%/87% in the inferior, 31%/85% in the lateral. WT were 67%/93% in the septum, 67%/79% in the inferior, and 59%/81% in the septum. The area under ROC curve was WM 0.63, WT 0.85 (p < 0.005 between WM and WT) in the septum, in inferior WM 0.77, WT 0.80 (p = 0.57), in anterior WM 0.86, WT 0.87 (p = 0.095), in lateral WM 0.68, WT 0.78 (p = 0.037). CONCLUSION: In normal profile, the % tracer uptake in the anterior wall decreased in females, but WM and WT did not show significant difference in each region affected this influence. The septal WM was decreased in the normal profile and ability to diagnose regional function was also decreased compared with WT. Thus, we can conclude that WT is preferable for detecting septal functional abnormality.

Aged↗

Treatment guidelines for geriatric mood disorders.

The authors reviewed the literature on the pharmacotherapy of geriatric mood disorders. Based on the evidence available, we have proposed: (i) that although any antidepressant is assumedly equal in antidepressive efficacy, ones with weak anticholinergic and antialpha1 effects are preferable in geriatric patients; (ii) that augmentation therapy with lithium and methylphenidate has modest evidence of efficacy in this population; (iii) that modified electroconvulsive therapy is safe and effective for severe and psychotic depression in the elderly; and (iv) that lithium remains the first choice for geriatric bipolar disorder, although its optimal serum level may be lower than in younger adults.

Adult↗

Questionnaire survey on the prescribing practice of Japanese psychiatrists for mood disorders.

The answers to a questionnaire on the practical prescription in mood disorders from 298 Japanese psychiatrists was obtained. As the first-line treatment, a majority of respondents chose newer tricyclic agents (TCA) or non-TCA for moderate depression and older TCA for severe depression both with and without psychotic features. Combination therapy with antidepressants and anxiolytics was fairly popular in moderate depression, while antidepressant/neuroleptic combination was more common in severe psychotic depression. Sulpiride was the most favored drug for dysthymia. Although lithium was the most popular for bipolar mania, respondents were divided on the treatment of bipolar depression.

Anti-Anxiety Agents↗

[Assessment of regional quantitative analysis by ECG-gated myocardial SPECT after coronary artery bypass surgery].

PURPOSE: ECG-gated myocardial SPECT (G-SPECT) was performed before and after coronary artery bypass surgery (CABG) to investigate how this operation would affect the assessment of regional quantitative analyses. METHODS: Nineteen patients with coronary artery disease underwent G-SPECT before and 1 month after uncomplicated CABG. 99mTc-MIBI 740 MBq was injected at rest, then G-SPECT was performed 60 min later. Regional ejection fraction (rEF), wall motion (WM), systolic wall thickening (WT) and % tracer uptake were evaluated by quantitative gated SPECT program (QGS). Parameters were obtained quantitatively in 16 segments based on the functional bull's eye map. RESULTS: Percent tracer uptake increased in septum from 75 +/- 11% to 78 +/- 11% (p < 0.001), while WT did not change (40 +/- 19% to 41 +/- 20%) after CABG. However, in septum rEF decreased from 17 +/- 13% to 6 +/- 9% (p < 0.001) and WM decreased in septum from 1.6 +/- 1.1 mm to 0.6 +/- 0.9 mm (p < 0.001). CONCLUSION: Significant reduction of rEF and WM despite of no deterioration of WT and % tracer uptake suggested that rEF and WM were affected by pseudoparadoxical asynergy after uncomplicated CABG. For the evaluation of regional function after CABG by G-SPECT, WT might be the preferred parameter.

Aged↗