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Biomedical subjects

Yuji Takahashi

Publications and source records attributed to Yuji Takahashi.

At least 37 records · Page 2Linked to original sources

A reduction in intraovarian arterial blood flow resistance after ovulation is necessary to achieve pregnancy in natural cycle.

PURPOSE: Color Doppler imaging permits the accurate localization of vessels and high-frequency pulsed Doppler ultrasonography has improved the resolution of flow velocity waveforms. In this study, intraovarian arterial blood flow before and after follicle rupture in the natural cycle was examined using transvaginal color flow Doppler imaging and changes in intraovarian arterial resistance in relation to the outcome of infertility treatment was analyzed. METHODS: In a prospective study, 227 spontaneous cycles in 118 infertile patients who were undergoing infertility treatment at the division of Reproductive Medicine in our center were recruited in this study. The impedance to flow in intraovarian vessels was measured by means of transvaginal color flow Doppler imaging during the periovulatory period in the natural cycle of all patients. The pulsatility index (PI) of intraovarian arterial blood flow and pregnancy rate was evaluated. RESULTS: On the basis of PI values before and after follicular rupture, 227 cycles were classified into severely decreased (113 cycles) and not-severely decreased groups (114 cycles). The pregnancy rate per cycle in the severely decreased group was 18.6% (21/113), significantly higher than that in the not-severely decreased group (7/114; 6.1%, p = 0.004). The miscarriage rate was similar in the two groups. CONCLUSIONS: A reduction in intraovarian blood vessel resistance is necessary to achieve pregnancy in a natural cycle.

Blood Flow Velocity↗

Homeobox B3, FoxA1 and FoxA2 interactions in epithelial lung cell differentiation of the multipotent M3E3/C3 cell line.

HOM/C homeobox (Hox) and forkhead box (Fox) factors are reported to be expressed in the foregut endoderm and are subsequently detected in a spatio-temporal pattern during lung development. Some of these factors were reported to influence the expression of lung marker proteins or to modulate lung development. To clarify the molecular mechanisms for generating functional lung cells from progenitor cell populations, we introduced the forkhead box factors, FoxA1 and FoxA2, and the homeobox factor, HoxB3, into the differentiation process in a multipotent hamster lung epithelial M3E3/C3 cell line. Ectopic expression of FoxA2 promoted differentiation to Clara-like cells with up-regulation of the expression of the lung marker proteins, Clara cell-specific 10-kDa protein and surfactant protein-B. In contrast, FoxA1 repressed the differentiation. HoxB3 transfection induced FoxA2 expression transiently at the pre-differentiation stage. The endogenous HoxB3 expression level decreased at later stages of Clara-like cell differentiation, and the attenuation was enhanced by FoxA2 transfection. HoxB3 is a putative upstream regulator that enhances FoxA2 expression at the pre-differentiation stage. In addition, we found that the expression of HoxA4, HoxA5, and HoxC9 increased differentially during Clara-like cell differentiation. These results suggest that HoxB3 may be a putative positive regulator of FoxA2 expression at the pre-differentiation stage, and those interactions of Fox factors and Hox factors could participate in Clara cell differentiation.

Animals↗

Matrix metalloproteinase inhibitor MMI-166 inhibits lymphogenous metastasis in an orthotopically implanted model of lung cancer.

Matrix metalloproteinases (MMP) are considered to be critically involved in tumor invasion and the metastasis of various cancers. MMI-166 is a selective inhibitor of matrix metalloproteinase (MMP-2, MMP-9, and MMP-14). The purpose of this study was to evaluate the effects of MMI-166 on both the growth of the implanted tumor and the lymph node metastasis of the mediastinum and prolonging the life span, using an orthotopic implantation model of the Ma44-3 cancer cell line. We examined the anti-invasive effect of MMI-166 in lung cancer cell lines using an in vitro invasion assay. Next, we examined the anticancer effect of MMI-166 in vivo. MMI-166 (200 mg/kg body weight) or a vehicle was administered orally to the orthotopically implanted lung cancer model. MMI-166 dose-dependently inhibited the invasion of cancer cell lines with expressions of MMP-2 and/or MMP-9 in vitro. In vivo, MMI-166 significantly inhibited mediastinal lymph node metastasis in this orthotopic model (weight of the mediastinum: control, 0.089 +/- 0.009 versus MMI-166, 0.069 +/- 0.008 mg; P = 0.005; metastatic area: control, 93,495 +/- 55,747 versus MMI-166, 22,747 +/- 17,478 pixels; P = 0.045). MMI-166 prolonged the life span by 6 days in median survival time in the orthotopically implanted model (P = 0.039). These results showed that MMI-166 could possibly inhibit lymph node metastasis and prolong the life span in lung cancer patients.

Animals↗

Intestinal gene expression in TNBS treated mice using genechip and subtractive cDNA analysis: implications for Crohn's disease.

So far it has proven difficult to identify a causative gene(s) or gene product initiating the events that lead to inflammation of the intestinal mucosa and, ultimately, progression to Crohn's disease (CD), an inflammatory bowel disease. However, gene transcripts identified in the intestine of trinitrobenzene sulfonic acid (TNBS)-treated mice might suggest a clue, and even represent candidate genes leading to inflammation and mucosal damage, and to subsequent fibrosis. In the present study, DNA microarray (13000 transcripts) methodology was applied to mucosal RNA extracted from TNBS-treated mice, some transcripts of which were validated via cDNA subtraction and RT-PCR analyses. Intestinal biopsy samples from CD patients were then analyzed using cDNA mini-array (1300 cDNAs), focusing on gene transcripts associated with cancer and immunity. Mini-array results revealed transcript changes similar and also dissimilar to those found from the DNA microarray analysis. These changes, previously known or newly identified, possibly occurring during the initial and progressive stages of inflammatory conditions may provide a clue to identify marker transcripts and/or targets for the development of future gene therapy.

Animals↗

Bovine paraoxonase 1 activities in serum and distribution in lipoproteins.

Paraoxonase 1 (PON1) is an enzyme associated with high-density lipoprotein (HDL) and has a protective effect against oxidation of lipoproteins in mammals. We investigated PON1 enzyme activities in bovine serum and its distribution among bovine serum lipoproteins. Paraoxonase activity and arylesterase activity in serum (152 Holstein cows and 42 Japanese Blacks) were 275 +/- 55 U/ml and 130 +/- 27 U/ml (mean +/- SD), respectively. There was a high correlation (r=0.962) between the two enzyme activities, and the activity ratio of paraoxonase/arylesterase did not exhibit individual variation. More than 85% of both paraoxonase and arylesterase activities were detected in the HDL fraction separated by ultracentrifugation. The 43-kDa protein in the HDL fraction was identified as bovine PON1 by N-terminal amino acid sequence analysis. Bovine PON1 was purified by ultracentrifugation and preparative sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and an anti-bovine PON1 antiserum was developed. The concentration of PON1 protein determined by immunoblotting was closely correlated (r=0.976) with paraoxonase activity in serum. Bovine HDL was further fractionated into subpopulations, and the distribution of PON1 was examined. Paraoxonase activity and PON1 protein increased with decreasing HDL size and approximately 60% of total paraoxonase activity was distributed in the heavy HDL fraction. The different distributions of PON1 among HDL subpopulations might be concerned to the function and metabolism of bovine HDL.

Animals↗

[Coronary sinus ostial atresia with thrombus: a case report].

An 82-year-old woman presented with mitral regurgitation and atrial fibrillation. She was hospitalized for further examination of cardiac thrombus detected by transthoracic echocardiography. No definitive diagnosis could be made based on computed tomography and magnetic resonance imaging. Intravenous contrast echocardiography suggested a coronary sinus thrombus. Coronary angiography showed coronary sinus ostial atresia. Multislice computed tomography confirmed the presence of thrombus in the enlarged coronary sinus with coronary sinus ostial atresia and persistent left superior vena cava. Persistent left superior vena cava is present in 3% of patients with congenital heart disease. Persistent left superior vena cava is detected by chance during cardiac catheterization for other conditions in patients without cardiac malformations. The present case was detected at an advanced age, and in the absence of prior symptoms.

Aged↗

[Effects of ethanol ingestion on glucose tolerance in people with different genotypes of ALDH2].

Effects of alcohol drinking on glucose tolerance were investigated in male healthy subjects (20-36 years old) with different phenotypes of aldehyde dehydrogenase 2 (ALDH2). Oral glucose tolerance test was performed in each subject twice with and without simultaneous oral ingestion of ethanol. Simultaneous oral ingestion of ethanol (10 g) significantly enhanced the early increase in plasma insulin concentration at 30 min after ingestion of glucose (100 g) in subjects with normal ALDH2 phenotype, while the increase in early insulin response due to alcohol was slight and not significant in those with atypical ALDH2. On the other hand, the early increase in plasma glucose concentration at 30 min after glucose inges-tion was not affected by simultaneous ethanol drinking in both groups of subjects with normal and atypical ALDH2 phenotypes. Thus, drinking alcohol together with a simple sugar causes enhancement of early insulin response, which is more prominent in people with normal ALDH2 phenotype than in those with atypical ALDH2 phenotype.

Adult↗

Microscopic analysis of the chromium content in the chromium-induced malignant and premalignant bronchial lesions of the rat.

OBJECTIVE: Our previous studies demonstrated that the frequency of gene instability in lung cancer of chromate workers was very high, but the frequencies of the p53 and ras gene mutations were low. To clarify the carcinogenesis of chromate in the lung, we established a chromate-induced cancer model in the rat proximal airway and examined the relationship between chromium accumulations and the chromium-induced cancer and premalignant bronchial lesions of the rat. METHODS: Fifteen male, bred, 12-week-old Jcl-Wister rats were used. A pellet of strontium chromate were inserted into the bronchus of the rats. The rats were sacrificed 9 months after the pellet was inserted. We pathologically examined the region of the bronchi to which the pellet was attached. We quantified the amount of chromium accumulation in the bronchial lesions using a microscopic X-ray fluorescence analyzer. RESULTS: Of the 15 rats, 1 rat had a lesion of squamous cell carcinoma (SCC), 7 rats had carcinoma in situ (CIS) or dysplasia, 8 rats had squamous metaplasia, and 5 rats had goblet cell hyperplasia. The amounts of chromium accumulation in normal epithelium (n=24), goblet cell hyperplasia (n=14), squamous metaplasia (n=8), and dysplasia plus CIS plus SCC (n=9) were 500+/-1354, 713+/-1062, 941+/-1328, and 3511+/-4473 (mean+/-SD) counts/s/mA, respectively. The amount of chromium accumulation was significantly increased according to the progression of malignant change of the bronchial epithelium (Spearman's correlation coefficient by ranks, rs=0.454, P<0.01). CONCLUSIONS: The amount of chromium accumulation was significantly increased according to the progression of malignant change of the bronchial epithelium. Examining the genetic alterations of histologic changes in this model was helpful in elucidating the process of carcinogenesis of chromium in the lung.

Animals↗

Is the ClC-2 chloride channel involved in the Cl- secretory mechanism of gastric parietal cells?

It has been controversial whether the ClC-2 chloride channel is involved in hydrochloric acid secretion of gastric parietal cells. Here, we investigated whether ClC-2 is the apical Cl- channel associated with gastric acid secretion. Two anti-ClC-2 antibodies used in this study reacted with cloned ClC-2 protein expressed in HEK293 cells. In isolated rabbit gastric glands, significant expression of ClC-2 mRNA was observed, but the presence of ClC-2 protein was not clear. Furthermore, no expression of ClC-2 protein was observed in isolated rat and human gastric mucosa. Immunohistochemistry on the rat gastric mucosa showed no significant expression of ClC-2 protein in the parietal cells which showed abundant expression of H+,K+-ATPase. These results indicate that ClC-2 may not be a Cl- -transporting protein for gastric acid secretion in parietal cells.

Aged↗

Up-regulation of Na(+),K(+)-ATPase alpha 3-isoform and down-regulation of the alpha1-isoform in human colorectal cancer.

We investigated expression levels of Na(+),K(+)-ATPase alpha-isoforms and their ATPase activities in human colorectal cancer tissue and the accompanying normal mucosa. A decrease in expression of the alpha1-isoform protein was observed in all sampled cancer tissues compared with the normal mucosae. The level of ouabain (5 microM)-sensitive Na(+),K(+)-ATPase activity in carcinomas was 81+/-5% that of in the normal mucosae. The mRNA expression of alpha2- and alpha 4-isoforms was decreased in almost all the carcinoma samples. Interestingly, the expression level of the alpha 3-isoform protein in the cancer tissue was higher than that of the normal mucosa. These results indicate that a decrease in the alpha1-isoform expression and an increase in the alpha 3-isoform expression may be associated with colorectal cancer.

Asian People↗

Diazepam reduces both arterial blood pressure and muscle sympathetic nerve activity in human.

It is known that benzodiazepines have a hypotensive effect, but the mechanism has not been well elucidated yet. To clarify whether this effect is due to central or peripheral mechanism, we administered 5 mg of diazepam or saline intravenously to healthy volunteers and assessed the change in blood pressure, heart rate, muscle sympathetic nerve activity and heart rate variability. After diazepam administration, systolic and mean blood pressure decreased significantly. Muscle sympathetic nerve activity was also significantly reduced but heart rate did not change, whereas the variables of spectral analysis of heart rate variability did not show significant change. We concluded that the hypotensive effect of diazepam in human is mainly due to the central mechanism.

Action Potentials↗

Reduction of lipopolysaccharide-induced cyclooxygenase-2 expression in diabetic arteries.

In order to clarify the effects of diabetes mellitus on induction of cyclooxygenase (COX)-2 and subsequent prostaglandin production in blood vessels, we investigated lipopolysaccharide (LPS)-induced COX-2 induction and prostacyclin production in aortic strips isolated from streptozotocin-induced diabetic rats and vehicle-injected control rats. The rats at 10 weeks after injection of streptozotocin had significantly lower body weights and higher serum glucose levels compared with those in the control rats. LPS stimulation resulted in a marked increase in the release of prostacyclin from the aortic strips. This increase was abolished in the presence of indomethacin or cycloheximide but was not affected by removal of the endothelium. In diabetic aortae, both LPS-induced prostacyclin production and COX-2 induction were diminished compared with the control aortae. No significant difference in COX-1 expression was observed between diabetic and control aortae. The diminution of LPS-induced COX-2 expression was also observed in alveolar macrophages isolated from diabetic rats. These results suggest that COX-2 expression and subsequent prostacyclin production in response to LPS are selectively attenuated in diabetic blood vessels.

Animals↗

Successful use of zonisamide for central poststroke pain.

UNLABELLED: We present 2 patients with severe and intractable central poststroke pain (CPSP) after right posterolateral thalamic infarcts who were successfully treated with zonisamide. The mechanism of action was presumed to be the suppression of overacting thalamic relay neurons by blockade of low voltage-activated calcium channel or by increasing gamma-aminobutyric acid (GABA) release. Zonisamide can be one of the therapeutic options for severe CPSP and might provide an insight into the pathogenesis of CPSP. PERSPECTIVE: The blockade of T-type VGCC or the increase in GABA release caused by zonisamide presumably suppresses abnormal activities of thalamic sensory neurons.

Anticonvulsants↗

Preoperative sonographic evaluation is a useful method of detecting contralateral patent processus vaginalis in pediatric patients with unilateral inguinal hernia.

BACKGROUND/PURPOSE: To analyze the value of ultrasound scan (US) in the preoperative identification of a contralateral patent processus vaginalis (CPPV), the authors investigated the presence of CPPV by US in children with clinically diagnosed unilateral inguinal hernias. METHODS: Three hundred forty-eight patients (168 boys and 180 girls) with unilateral inguinal hernia underwent US examination using a 7.5-MHz linear transducer. If a CPPV was visible as a hydrocele owing to the inflow of physiologic ascites into a processus vaginalis on straining, then US scanning was performed while the patient was at rest and while inducing straining by standing or crying. A groin with a hydrocele in the inguinal canal on straining was diagnosed as a CPPV and was explored bilaterally through surgery. The US findings were compared with surgical results. RESULTS: In 348 patients, 78 cases (22.4%) were diagnosed by US as patients with a CPPV; these patients underwent bilateral surgery. Seventy-four of 78 cases (94.9%) were confirmed surgically as patients with CPPV. CONCLUSIONS: A CPPV was detected correctly by US in 74 of 348 patients (21.3%) with clinically diagnosed unilateral inguinal hernias. US is a noninvasive and accurate method for evaluating the presence of a CPPV.

Child↗

Quantitative trait locus analysis of plasma cholesterol and triglyceride levels in C57BL/6J x RR F2 mice.

A highly significant cholesterol quantitative trait locus (QTL) (Cq6) was identified on chromosome 1 in C57BL/6J x RR F2 mice. The Cq6 was located over the gene for apolipoprotein A-Il (Apoa2), and the RR allele was associated with increased plasma cholesterol. C57BL/6J has Apoa2a alleles and RR has Apoa2b alleles. Three different Apoa2 alleles are known on the basis of amino acid substitutions at four residues. Analysis with partial Apoa2 congenic strains possessing Apoa2a, Apoa2b, and Apoa2C alleles revealed that the Apoa2b allele is unique in the ability to increase cholesterol among the three Apoa2 alleles, and that the Ala-to-Val substitution at residue 61 may be crucial as far as cholesterol metabolism is concerned. We also investigated the question of whether the Apoa1 gene is responsible for the cholesterol QTLs (Cq4 and Cq5) that had been identified previously on chromosome 9 in C57BL/6J x KK-Ay/a F2 and in KK x RR F2, but not in C57BL/6J x RR F2 mice. Similar to Apoa2 alleles, three different Apoal alleles with two successive amino acid substitutions were revealed among the strains. However, we could not correlate Apoal polymorphisms with the occurrence of QTLs in these three sets of F2 mice.

Alleles↗

A MAP kinase cascade that controls plant cytokinesis.

Several components of mitogen-activated protein kinase (MAPK) cascades have been identified in higher plants and have been implicated in cellular responses to a wide variety of abiotic and biotic stimuli. Our recent work has demonstrated that a MAP kinase cascade is involved in the regulation of cytokinesis in plant cells. The MAP kinase cascade in tobacco includes NPK1 MAPK kinase kinase, NQK1 MAPK kinase, and NRK1 MAPK, and its activation is triggered by the binding of NACK1/2 kinesin-like protein to the NPK1 MAPK kinase kinase at the late M-phase of the cell cycle. We refer to this cascade as the NACK-PQR pathway. In this review, we introduce a mechanism for the regulation of plant cytokinesis, focusing on the role of the NACK-PQR pathway.

Arabidopsis↗