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T Harada

Publications and source records attributed to T Harada.

At least 73 records · Page 4Linked to original sources
PubMed2001

Role of cytokines in endometriosis.

OBJECTIVE: To review the literature on the role of cytokines in the pathogenesis of endometriosis and endometriosis-associated infertility. DESIGN: Pertinent studies were identified by a computer search of MEDLINE. References of selected articles were hand-searched for additional citations. RESULT(S): Recent studies suggest that the peritoneal fluid of women with endometriosis contains an increased number of activated macrophages that secrete various local products, such as growth factors and cytokines. Levels of several cytokines were reported to be elevated in the peritoneal fluid of women with endometriosis. Because the peritoneal environment may be controlled by locally regulated factors, cytokines are believed to play a role in the development and progression of endometriosis and endometriosis-associated infertility. A possible pathogenic mechanism links cytokines with endometriosis. CONCLUSION(S): Cytokines, which are produced by many cell types including endometriotic tissues, play diverse roles in the pathogenesis of endometriosis and endometriosis-associated infertility. More studies about the specific role of these cells and soluble factors are needed to improve understanding of endometriosis and to develop novel therapies.

Ascitic Fluid↗
PubMed2001

Relationship between serum lipoprotein(a) level and thrombin generation to the circadian variation in onset of acute myocardial infarction.

A high incidence of acute myocardial infarction (AMI) has been reported between 06:00 and 12:00 h. This may be related to an abnormality in hemostasis. An association has been founded between the serum lipid level and coronary atherosclerosis, as well as the serum lipid level and a hemostatic abnormality. We investigated the association between the time of AMI, the level of serum lipid, and of hemostatic factor. Of the 42 subjects evaluated retrospectively, 20 had experienced an AMI between 06:00 and 12:00 h (group A), while 22 had developed an AMI during some other period (group B). All patients received emergency coronary angiography, which identified a total occlusion of coronary artery in the proximal portion of the left antecedent branch. The serum level of several lipid factors and of hemostatic factors were compared between the two groups. Characteristics of patients were similar in both groups. The serum levels of lipoprotein(a) (Lp(a)) and of thrombin-antithrombin III complex (TAT) were higher in group A than in group B, respectively. The level of other factors were similar in both groups. Group A showed a significant correlation between the level of Lp(a) and TAT, with a tendency (not statistically significant), toward a positive correlation between Lp(a) and PAI-1, and a negative correlation between Lp(a) and t-PA. In a subgroup that experienced AMI in the early morning, a higher level of Lp(a) was associated with an elevation of TAT, a marker for thrombin generation, and with the level of fibrinolytic factor. This suggests that Lp(a) is closely related to the increase in the early morning incidence of AMI via a change in the prothrombotic state.

Antithrombin III↗
PubMed2001

Effects of changes in stimulus level on phases of distortion product otoacoustic emissions.

Effect of changes in stimulus levels of both lower (f(1)) and higher (f(2)) stimulus tones on phases of 2f(1)-f(2) component of the distortion product otoacoustic emission (DPOAE) was examined in five normal hearing adults. The f(2) was fixed at 4004 Hz in all of the measurements, and the stimulus frequency ratio (f(2)/f(1)) was varied from 1.15 to 1.3. Change of the level of lower stimulus tone (L(1)) and the level of higher stimulus tone (L(2)) showed different effects on the DPOAE phases. The phase lags increased with increasing L(1), when f(2)/f(1) was above 1.22, whereas the phase gains increased with increasing L(1), when f(2)/f(1) was below 1.22. On the other hand, the difference in L(2) minimally affected DPOAE phase at most f(1)s. The previous studies about basilar membrane vibration revealed that phase lags increase with increasing stimulus level, when the stimulus frequency is below the best frequency, while phase gains increase with increasing stimulus level, when the stimulus frequency is above the best frequency, and the effect of phase change in stimulus level diminished, when the stimulus frequency was far above the best frequency. Based on the comparison between the results of the present study and the previous findings of others concerning basilar membrane vibration, the DPOAE generation site is assumed to be located at apical of the peak of the f(2) traveling wave.

Acoustic Stimulation↗
PubMed2001

Hearing impairment and quality of life for the elderly in nursing homes.

OBJECTIVE: The purpose of this study is to find out the effects of hearing impairment on the QOL of nursing home residents. METHODS: We constructed the self-assessment questionnaire designed for evaluating the QOL for the elderly in nursing homes. The questionnaire is constructed of physical, social, communicational and psychological states. It was administered to 60 subjects >65 years of age (mean age: 79 years) living in nursing homes, with hearing threshold levels in the better ear ranging from normal to severe and their response were analyzed. RESULTS: Chronbach's alpha-values of the questionnaire obtained ranged from 0.66 to 0.91 and was 0.84 overall. The reliability and validity of the questionnaire as well as its brevity, simplicity, ease of administration and interpretation, all satisfied its use in assessing the QOL of the elderly in nursing homes. It tended to decrease the points of communication scale, sociability scale and psychological scale (PGC Morale Scale) accordingly to elevate the threshold. As for subscales of communication, hearing disability was correlated statistically to the sociability and psychological. CONCLUSION: Our questionnaire is regarded as a useful tool for evaluating the QOL of the elderly. Hearing loss affects the communication, sociability and psychological aspect of the QOL for the elderly in the nursing homes.

Aged↗
PubMed2001

Identification of ephrin-A3 and novel genes specific to the midbrain-MHB in embryonic zebrafish by ordered differential display.

Development of the tectum and the cerebellum is induced by a reciprocal inductive signaling between their respective primordia, the midbrain and the midbrain/hindbrain boundary (MHB). We set out to identify molecules that function in and downstream of this reciprocal signaling. Overexpression of LIM domain of the transcription factor Islet-3 (LIM(Isl-3)) leads to inhibition of this reciprocal signaling and to resultant defects in tectal and cerebellar development. We therefore searched for genes that may be either up- or down-regulated by overexpression of LIM(Isl-3) by comparing the gene expression profiles in the midbrain and the MHB of normal embryos and embryos in which Islet-3 function was repressed, using a combination of ordered differential display and whole-mount in situ hybridization. Among genes identified in this search, two cDNA fragments encoded Wnt1 and FGF8, which are already known to be essential for the reciprocal signaling between the midbrain and the MHB, confirming the effectiveness of our strategy. We identified four other partial cDNA clones that were specifically expressed around the MHB, ten cDNAs specifically expressed in the tectum, and three cDNAs expressed in neural crest cells including those derived from the midbrain level. The ephrin-A3 gene was specifically expressed in posterior tectum in a gradient that decreased anteriorly. Although ephrin-A2 and ephrin-A5 have been reported to be expressed in the corresponding region in mouse embryos, the superior/inferior colliculi, mouse ephrin-A3 is not expressed prominently in this region, suggesting that the role of ephrin-A3 in brain development may have been altered in the process of brain evolution.

Amino Acid Sequence↗
PubMed2001

ERK induces p35, a neuron-specific activator of Cdk5, through induction of Egr1.

The classical mitogen-activated protein kinase (MAPK; also known as extracellular-signal-regulated kinase), ERK cascade has been shown to have a crucial role in cell proliferation and differentiation. In PC12 cells, sustained activation of ERK induced by nerve-growth factor (NGF) is essential for neuronal differentiation. However, downstream targets of ERK that are essential for neuronal differentiation have not been defined. Here we show that NGF induces strong, sustained expression of p35, the neuron-specific activator of cyclin-dependent kinase 5 (Cdk5), through activation of the ERK pathway. The induced kinase activity of Cdk5 is required for NGF-induced neurite outgrowth. Our results indicate that sustained activation of ERK is necessary and sufficient for strong induction of p35. Furthermore, the transcription factor Egr1, is induced by NGF through the ERK pathway and mediates induction of p35 by ERK. Our results thus define an essential signalling pathway, downstream of ERK/MAPK, that leads to neuronal differentiation.

Animals↗
PubMed2001

Light conditions during sleep period and sleep-related lifestyle in Japanese students.

The effects of light conditions during night sleep on sleep habits and morning-evening preference were studied in Japanese students (18-28 years old). Students who usually used fluorescent or non-fluorescent light on the room ceiling, wall or desk preferred to have a daytime nap significantly later (Mean: 14:50 h) than those who used no light (13:34 h). Students who used no curtain or a half-transparent lace-curtain showed shorter sleep latency (duration from going-to-bed to sleep-onset) than those who used a curtain which shuts off lights from outside. Light conditions during the middle of night and early in the morning may affect the timing of sleep in Japanese students based on the circadian system.

Adolescent↗
PubMed2001

Enhanced expression of complement C5a receptor mRNA in human diseased kidney assessed by in situ hybridization.

BACKGROUND: Anaphylatoxin C5a mediates inflammatory responses through interaction with a specific C5a receptor (C5aR), the expression of which is thought to be restricted to peripheral blood leukocytes. Although the presence of C5aR on cultured mesangial cells and tubular epithelial cells has recently been documented, the tissue distribution of C5aR in diseased kidney has not yet been determined. METHODS: Immunohistochemistry and nonradioactive in situ hybridization for C5aR were performed in 34 tissue samples of kidneys from patients with various renal diseases, including 4 with minimal change nephrotic syndrome (MCNS), 5 with membranous nephropathy (MN), and 25 with mesangial proliferative glomerulonephritis (mesGN; 15 patients with IgA nephropathy, 5 with non-IgA mesGN, and 5 with lupus nephritis). Normal portions of surgically resected kidney served as the control. RESULTS: In normal kidneys, C5aR protein was detected in tubular epithelial cells, while C5aR mRNA was detected in a few glomerular cells, tubular epithelial cells, and vascular endothelial and smooth muscle cells. In MCNS, the distribution of C5aR protein and mRNA was similar to that in normal kidneys. In MN and mesGN, C5aR protein and mRNA were detected in mesangial cells, glomerular epithelial and endothelial cells, Bowman's capsule cells, tubular cells, infiltrating cells, and vascular endothelial and smooth muscle cells. The glomerular expression of C5aR mRNA and protein correlated positively with the degree of mesangial hypercellularity and mesangial matrix expansion in mesGN. In the tubulointerstitium, interstitial expression of C5aR mRNA correlated positively with the degree of tubular atrophy and interstitial broadening in mesGN. Furthermore, the interstitial expression of C5aR mRNA correlated positively with the level of serum creatinine. CONCLUSIONS: Our results indicate that renal cells produce C5aR and that activation of C5a/C5aR pathway on renal cells may be involved in tissue injury in mesGN.

Adolescent↗
PubMed2001

Investigation on diabetic autonomic neuropathy assessed by power spectral analysis of heart rate variability in WBN/Kob rats.

This article investigates the development of cardiovascular autonomic dysfunction caused by diabetes mellitus. We performed power spectral analysis of heart rate variability in WBN/Kob rats as a model of spontaneous diabetes. The heart rate of the rats was measured continuously for 24 hours with an implanted telemetric transmitter, and power spectral analysis of heart rate variability was performed on continuous electrocardiograms. At 4 to 5 months of age, the rats indicated a tendency toward a decrease in plasma insulin concentration without hyperglycemia. At 8 to 9 months of age, they showed remarkable hyperglycemia, loss of the circadian rhythm of the heart rate, and reversion or loss of the circadian rhythm of the blood pressure. By the power spectral analysis of heart rate variability, it became apparent that the circadian rhythm of the low frequency/high frequency ratio was absent even in prediabetic WBN/Kob rats. In addition, the circadian rhythms of the high-frequency power level and low frequency/high frequency ratio were absent in diabetic WBN/Kob rats. These findings indicate that the autonomic nervous system in WBN/Kob rats is progressively damaged from the prediabetic to diabetic state. In conclusion, diabetic autonomic neuropathy may be characterized by the appearance of sympathetic overactivity that precedes the impairment of parasympathetic activity.

Animals↗
PubMed2001

Proliferation in the posterior region of the lens of c-maf-/- mice.

PURPOSE: To examine the involvement of the c-maf gene in the proliferation of the lens cells. METHODS: Eyes of the E13 and E18 stages of the wild-type and c-maf-/- mice were analyzed by BrdU incorporation assay, TUNEL assay and immunocytochemistry using a anti-P27(KIP1) and a anti-P57(KIP2) antibody. RESULTS: In the E13 and E18 c-maf mutant lens, BrdU-positive cells were detected at the posterior region of the lens. Cell-cycle inhibitor P27(KIP1) and P57(KIP2) were expressed in the equatorial and posterior region of the lens of both wild-type and c-maf-/- lenses. CONCLUSION: These results suggest that the expression of c-maf is required for differentiation and cell cycle arrest of lens fiber cells. It is also suggested that P27(KIP1) and P57(KIP2) were not involved in the continued proliferation of posterior region of the c-maf-/- lens.

Animals↗
PubMed2001

Immunohistochemical study on hypoxia in spontaneous polycystic liver and kidney disease in rats.

Hypoxia-inducible factor (HIF) mediates homeostatic responses to hypoxia and activates transcription of hypoxia-inducible genes including vascular endothelial growth factor (VEGF). The aim of this study was to examine the expressions of VEGF, HIF-1alpha and HIF-3alpha in spontaneously occurring hepatorenal polycystic lesions in two Sprague-Dawley (Crj:CD) rats. Hepatic multiple cysts were derived from the interlobular and large bile ducts, while renal cysts were from the collecting ducts and distal tubuli. These findings were confirmed by a lectin peanut agglutinin (PNA) histochemistry. In the polycystic liver, VEGF immunoreaction was strongly evident in the cytoplasm of hepatocytes, whereas expression of HIF-3alpha, but not HIF-1alpha, was found in a few nuclei of hepatocytes. In the polycystic kidney, VEGF immunoreaction was increased in the cytoplasm of collecting ducts and distal tubuli, whereas nuclear expression of HIF-1alpha and HIF-3alpha was evident in the proximal tubuli and thin loop of Henle, respectively. The results suggest that hypoxia-related molecules may be induced by cystic alterations in a heterogeneous appearance.

Animals↗
PubMed2001

Recurrent septicemia caused by Streptococcus canis after a dog bite.

Human infection with Streptococcus canis is extremely rare. We describe herein a case of septicemia with cellulitis caused by S. canis in a 75-y-old woman, which developed 2 weeks after a dog bite. Macrorestriction analysis with pulsed-field gel electrophoresis demonstrated that the organism had been transmitted by means of a dog bite to her hand.

Aged↗
PubMed2001

Parental enforcement of bedtime during childhood modulates preference of Japanese junior high school students for eveningness chronotype.

We examined the effect of home bedtime discipline during childhood on morningness and eveningness (M-E) preference by Japanese junior high school students. M-E was assessed by the M-E Questionnaire (MEQ) of Torsvall and Akerstedt (the higher the score, the greater the preference for morningness), and parental determination of bedtime during childhood was ascertained using an original questionnaire. The average M-E score of adolescents living in urban Kochi City (mean +/- SD; 15.10 +/- 3.42) was significantly lower (P < .01) than the score of those in suburban districts (16.14 +/- 3.44). Overall, 43.1% of the junior high school students in Kochi City compared to 53.0% of the students living in suburban districts had their bedtime decided during childhood by parents (P < .01). In Kochi City, the M-E score for boys (14.62 +/- 3.51) was lower (P < .01) than girls (15.53 +/- 3.28). During childhood, parents decided the bedtime for 49% of the girls compared to 36.6% of the boys (P < .01). Boys whose bedtime was not decided by parents during childhood had a somewhat stronger preference for eveningness (14.20 +/- 3.53) (P < .05) compared to those whose bedtime was decided by parents (15.12 +/- 3.36). The results suggest bedtime discipline at home during childhood has an effect on adolescent chronotype, modulating the extent of shift to evening ness in Japanese junior high school boys in particular.

Adolescent↗
PubMed2001

Menstrual cycle-specific inhibition of endometrial stromal cell proliferation by oncostatin M.

We have investigated the possible roles of oncostatin M (OSM), which is a member of the interleukin-6 family of cytokines, in endometrial and endometriotic stromal cell growth. Endometrial and endometriotic stromal cells were collected from the uterus or ovarian chocolate cysts. We observed the expression of mRNA transcripts for OSM, OSM receptor subunit beta, leukaemia inhibitory factor receptor subunit (LIFR), and glycoprotein 130 in endometrial and endometriotic stromal cells. We also examined the effects of OSM (0-50 ng/ml) and LIF (0-10 ng/ml) on endometrial and endometriotic stromal cell proliferation and evaluated the effects of OSM on endometrial stromal cell differentiation. The presence of 10-50 ng/ml OSM significantly suppressed endometrial stromal cell growth in secretory phase tissue but not in proliferative phase tissue. In contrast, stromal cells in endometriotic tissues were resistant to the inhibitory effects of OSM. Addition of LIF did not influence the growth of endometrial stromal cells. We also showed that 10 ng/ml OSM stimulated markers of differentiation causing increased prolactin secretion and cyclooxygenase-2 gene expression in endometrial stromal cells from the secretory phase. These results suggest that OSM may play a pivotal role in regulating the growth and differentiation of endometrial cells. Endometriotic cells may behave differently from normal endometrial cells in terms of the inhibitory response to OSM.

Antigens, CD↗
PubMed2001

In vitro refolding of porcine pepsin immobilized on agarose beads.

Since in vitro refolding of pepsin has long been attempted without success, it has been suspected that pepsin has no intrinsic refolding ability. In the present study, in order to eliminate unfavorable intermolecular interactions bringing about aggregation and autoproteolysis, we immobilized pepsin onto agarose beads. This technique enabled us to search extensively for appropriate refolding conditions without limitation of the refolding period. Renaturation of immobilized pepsin was observed exclusively at pH 3-5. This process was extremely slow and reached equilibrium after 300 h. Sixty percent of the proteolytic activity was recovered at pH 5. Addition of salts raised the recovery to 80% but had no significant effect on the refolding rate, suggesting that the salts mainly stabilize the native state of pepsin. This is the first report on the successful in vitro refolding of pepsin.

Animals↗
PubMed2001

High sensitivity of Nrf2 knockout mice to acetaminophen hepatotoxicity associated with decreased expression of ARE-regulated drug metabolizing enzymes and antioxidant genes.

Nrf2, which belongs to the basic leucine zipper (bZip) transcription factor family, has been implicated as a key molecule involved in antioxidant-responsive element (ARE)-mediated gene expression. In order to examine the role of Nrf2 in protection against xenobiotic toxicity, the sensitivity of nrf2 knockout mice to acetaminophen (N-acetyl-4-aminophenol (APAP)) was analyzed. The saturation of detoxification pathways after high levels of exposure to APAP is known to induce hepatotoxicity. Two factors important in its detoxification are UDP-glucuronosyltransferase (UDP-GT), an ARE-regulated phase-II drug-metabolizing enzyme, and glutathione (GSH), an antioxidant molecule whose synthesis depends on ARE-regulated gamma-glutamylcysteine synthetase (gammaGCS). Two- to 4-month-old male mice were orally administered a single dose of APAP at 0, 150, 300, or 600 mg/kg. Doses of 300 mg/kg APAP or greater caused death in the homozygous knockout mice only, and those that survived showed a greater severity in hepatic damage than the wild-type mice, as demonstrated by increased plasma alanine aminotransferase activity, decreased hepatic non-protein sulfhydryl (NPSH) content, and centrilobular hepatocellular necrosis. The high sensitivity of Nrf2-deficient mice was confirmed from observations made at 0, 2, 8, and 24 h after dosing with 300 mg/kg APAP; increased anti-APAP immunoreactivity was also noted in their livers at 2 h. Untreated homozygous knockout mice showed both a lower UDP-GT activity and NPSH content, which corresponded to decreased mRNA levels of UDP-GT (Ugt1a6) and the heavy chain of gammaGCS, respectively. These results show that Nrf2 plays a protective role against APAP hepatotoxicity by regulating both drug metabolizing enzymes and antioxidant genes through the ARE.

Acetaminophen↗