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Biomedical subjects

T Tabata

Publications and source records attributed to T Tabata.

At least 55 records · Page 3Linked to original sources
PubMed2000

Hedgehog creates a gradient of DPP activity in Drosophila wing imaginal discs.

Hedgehog (HH) and Decapentaplegic (DPP) direct anteroposterior patterning in the developing Drosophila wing by functioning as short- and long-range morphogens, respectively. Here, we show that the activity of DPP is graded and is directly regulated by a novel HH-dependent mechanism. DPP activity was monitored by visualizing the activated form of Mothers against dpp (MAD), a cytoplasmic transducer of DPP signaling. We found that activated MAD levels are highest near the source of DPP but are unexpectedly low in the cells that express dpp. HH induces dpp in these cells; it also attenuates their response to DPP by downregulating expression of the DPP receptor thick veins (tkv). We suggest that regulation of tkv by HH is a key part of the mechanism that controls the level and distribution of DPP.

Animals↗
PubMed2000

Formation of hippocampal synapses on patterned substrates of a laminin-derived synthetic peptide.

We created a new culture system which provides simple, stereotyped neuronal circuitries suitable for investigating synaptic events between mammalian central neurons. We used surface chemistry and laser-lithography to produce geometrical patterns of neuron-compatible substrate spaced by less neuron-compatible surfaces. The patterned substrates were composed of a laminin-derived synthetic peptide, PA22-2, and the spacing surfaces of either decyldimethylsilane (DDMS) or trimethylsilane (TMS). Dissociated rat hippocampal neurons survived on the patterned substrates for several days without the aid of glia and extended their neurites along the substrates. The TMS spacing surfaces appeared more favourable for the excitability development and axonal differentiation of the hippocampal neurons, but less favourable for the development of the resting conductance than the DDMS spacing surfaces. Furthermore, neurons grown on the patterned substrates frequently made synaptophysin-positive contacts with one another. Spontaneous post-synaptic currents recorded from such neurons suggest that these contacts were indeed functional synapses. When hippocampal neurons were plated at a very low density, they often formed circuitries consisting of only two neurons on the patterned substrate. Such a simple circuitry allowed us to analyse synaptic transmission in a single neuronal pair without the influence of the third neurons. With the clarity of analysis and the readiness of manipulation, our culture system would offer a powerful tool for studying development and functions of mammalian central synapses.

Animals↗
PubMed2000

Relationship between left atrial appendage function and plasma concentration of atrial natriuretic peptide.

BACKGROUND: It has been reported that the most intensely granuled cardiocytes secreting atrial natriuretic peptide (ANP) are located in the atrial appendages. AIMS: To evaluate the mechanisms of ANP release in congestive heart failure. METHODS AND RESULTS: The relationship between ANP and left atrial appendage (LAA) function was evaluated in 36 patients who underwent both transoesophageal echocardiography and cardiac catheterization. ANP level correlated positively with mean pulmonary capillary wedge pressure (mPCWP; r=0.75, P<0.0001), whereas it showed no significant correlation with the mean right atrial pressure. mPCWP correlated positively with the maximal LAA area (LAAa; r=0.79, P<0.0001) and negatively with the LAA ejection fraction during atrial contraction (LAA-EF; r=-0.61, P<0.0001) and peak late diastolic LAA emptying flow velocity (LAAF; r=-0.69, P<0.0001). ANP level correlated negatively with the LAA-EF (r=-0.56, P<0.001) and with LAAF (r=-0.61, P<0.0001). ANP level correlated more closely with the LAAa (r=0.79, P<0.0001) than with maximal LA volume (r=0.34, P<0.05). Multiple stepwise regression analysis selected LAAa as the only factor independently related to the plasma concentration of ANP (ANP=-22.4+28.6 LAAa, r=0.79, P<0.0001). CONCLUSIONS: We conclude that the factor most predictive for ANP in patients with left-sided cardiac dysfunction is distension of the LAA wall rather than elevation in the LA pressure or distension of the body of LA. This is consistent with the known distribution of ANP-secreting cardiocytes.

Adult↗
PubMed2000

Alcoholic fatty liver differentially induces a neutrophil-chemokine and hepatic necrosis after ischemia-reperfusion in rat.

Primary graft nonfunction of steatotic liver allograft is one of the factors causing shortage of donor livers. Ischemia/reperfusion (I/R) injury is an important contributory factor to primary graft nonfunction. In this study, we investigated the complex chain of events from transcription factor activation to necrosis through cytokine induction and apoptosis in steatotic rat liver after warm I/R. Rats with alcoholic or nonalcoholic fatty liver were subjected to hepatic warm I/R and compared with control rats. Rats fed an ethanol diet for 6 to 8 weeks developed severe hepatic necrosis accompanied by increased neutrophil recruitment after I/R, compared with rats with nonalcoholic fatty liver or control. Hepatic apoptosis as assessed by DNA fragmentation at 4 hours after I/R, however, increased to a similar degree in each of the 2 fatty liver models compared with the control. Alcoholic fatty liver exposed to I/R showed a rapid increase in nuclear factor-kappaB (NF-kappaB) binding activity at 1 hour after I/R, which preceded an increased expression of tumor necrosis factor alpha (TNF-alpha) and cytokine-induced neutrophil chemoattractant-1 (CINC-1). In contrast, nonalcoholic fatty liver did not show such potentiation of either NF-kappaB activation or cytokine induction after I/R. Our results have indicated that alcoholic fatty liver may differentially induce CINC-1 production and hepatic necrosis after I/R. Furthermore, our results suggest that apoptosis per se does not always lead to necrosis in the liver following I/R.

Animals↗
PubMed2000

Use of angiotensin II stress pulsed tissue Doppler imaging to evaluate regional left ventricular contractility in patients with hypertrophic cardiomyopathy.

There is controversy concerning whether contract-ility in the nonhypertrophied region of the left ventricular (LV) wall is impaired or normal in patients with hypertrophic cardiomyopathy (HCM). Global LV systolic function decreases with increases in afterload in this disease. This study was performed to identify abnormalities in regional LV contractility along the long and short axes in the setting of HCM with the use of angiotensin II (AT-II) stress pulsed tissue Doppler imaging (PTDI). Angiotensin II was administered intravenously to patients with asymmetric septal hypertrophy (HCM group, n = 21) and age-matched normal volunteers (N group, n = 12). We then measured the percent LV fractional shortening (%FS) and end-systolic circumferential LV wall stress by M-mode echocardiography, LV ejection fraction (LVEF) by 2-dimensional echocardiography, and time-velocity integral (TVI) of LV outflow velocity by pulsed Doppler echocardiography. The peak first and second systolic LV wall motion velocities along the long (L-Sw(1) and L-Sw(2)) and short (S-Sw(1) and S-Sw(2)) axes were measured in the LV posterior wall and ventricular septum with the use of PTDI. The end-systolic circumferential LV wall stress at baseline was significantly lower in the HCM group. The L-Sw(1) and L-Sw(2) for the posterior wall were significantly lower in the HCM group, but the S-Sw(1) and S-Sw(2) for the posterior wall and ventricular septum were similar in the two groups. The %FS, LVEF, TVI, and systolic PTDI variables along both axes for the posterior wall decreased significantly, and end-systolic circumferential LV wall stress increased significantly at AT-II doses of 0.005 or 0.010 microg/kg per minute in the HCM group. No significant changes were found in either group in the systolic PTDI variables (except for L-Sw(1)) for the ventricular septum with AT-II infusion. Contractility along the long and short axes of the nonhypertrophied LV wall is easily impaired with increases in afterload in patients with HCM, resulting in a decrease in global LV systolic function. We found AT-II stress PTDI to be a safe and useful technique for evaluating the regional LV systolic function in this disease.

Analysis of Variance↗
PubMed2000

Reappraisal of biochemical hepatitis C activity in hemodialysis patients.

We reappraised biochemical hepatitis C activity in hemodialysis patients in comparison with normal controls. A total of 111 hemodialysis patients and 66 healthy volunteer blood donors with hepatitis C virus (HCV) infection were consecutively enrolled. Serum alanine aminotransferase (ALT) levels were normal (< or =45 U/L) in 103 (93%) hemodialysis patients and 34 (52%) donors (p < 0.001). HCV viremic levels were lower in the hemodialysis group (p = 0.044), with no difference in the HCV genotype prevalence. During two-year follow-up, 60 (67%) of 90 hemodialysis patients and 13 (26%) of 50 donors showed persistently normal ALT levels (p < 0.001). For hemodialysis patients, however, the upper normal limit of ALT activity was reset at 25 U/L corresponding to the mean + 2 x SD for the normalized ALT distribution in 400 control patients. The adjusted ALT levels were initially normal in 73 (66%) hemodialysis patients and persistently normal in 19 (21%). Thus, ALT levels were the same for the two groups. GB virus C (GBV-C)/hepatitis G virus (HGV) coinfection found only in the hemodialysis group (10/111) had no influence on the disease. A relationship was noted between low disease activity and female gender in both groups. These findings indicate that biochemical hepatitis C activity in hemodialysis patients is similar to that in normal controls and should be monitored based on adjusted ALT levels.

Alanine Transaminase↗
PubMed2000

Ultrasonographic evaluation of lansoprazole-induced improvement of submucosal injury in patients with gastroesophageal reflux.

OBJECTIVE: Endoscopic ultrasonographic (EUS) changes in gastroesophageal reflux disease (GERD) after treatment with proton pump inhibitor have been poorly evaluated. We conducted a randomized, double-blind 12-wk clinical trial to compare the EUS effects of lansoprazole to histamine H2-receptor antagonist therapy in GERD. METHODS: Seventeen patients with reflux-related symptoms received 40 mg of famotidine for 6 wk or 30 mg of lansoprazole for 6 wk followed by 40 mg of famotidine or 30 mg of lansoprazole for another 6 wk, respectively. Patients underwent EUS before and at 6 and 12 wk after treatment. RESULTS: Before treatment, a variable degree of wall thickening was noted on EUS in the lower esophagus, compared with 20 normal subjects. After 6 wk of therapy, esophageal wall was significantly thicker in the famotidine group compared with the lansoprazole group (p<0.01). Surprisingly, thickening of esophageal wall and abnormal architecture were also detected in endoscopically negative reflux disease. Lansoprazole was superior to famotidine in reducing the thickness of esophageal wall. CONCLUSIONS: EUS was very useful for evaluation of submucosal injury in patients with GERD. EUS showed that a 6-wk course of lansoprazole therapy reduced thickening of esophageal wall, which was resistant to histamine H2-receptor antagonist therapy. Our results also suggest that inflammatory damage to the submucosal and muscle layers of the lower esophagus is the underlying mechanism of heartburn and associated symptoms in patients with endoscopically negative reflux disease.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed2000

Rare somatic inactivation of the multiple endocrine neoplasia type 1 gene in secondary hyperparathyroidism of uremia.

The molecular pathway of autonomous growth of the parathyroid glands in uremic patients is poorly understood. Loss of heterozygosity at the recently identified multiple endocrine neoplasia type 1 (MEN1) gene locus on chromosome 11q13 has been found in a subset of parathyroid glands from patients with refractory hyperparathyroidism. To clarify the role of the MEN1 gene in parathyroid tumorigenesis, we analyzed 81 parathyroid glands from 22 Japanese uremic patients for allelic loss on chromosomal arm 11q13 DNA using 3 flanking markers (PYGM, D11S4946, and D11S449) and for mutations of the MEN1-coding exons by PCR-based single strand conformation polymorphism analysis and sequencing. Allelic loss on 11q13 was observed in 6 glands (7%), and 1 of 6 demonstrated a previously unrecognized somatic frameshift deletion (331delG) of the MEN1 gene. This mutation would probably result in a nonfunctional menin protein, consistent with a tumor suppressor mechanism. Clinical and pathological characteristics of hyperparathyroidism were unrelated to the presence or absence of loss of heterozygosity on 11q13 and MEN1 gene mutations. These observations indicate that somatic inactivation of the MEN1 gene contributes to the pathogenesis of uremia-associated parathyroid tumors, but its role in this disease appears to be very limited.

Chromosome Mapping↗
PubMed2000

Mirror reversal simply explained without recourse to psychological processes.

This paper proposes a simple and definitive solution to the mirror reversal problem, "Why does a mirror reverse left and right but not up and down?" The solution is given by combining the inversion caused by the optical process of mirroring and the definition of the left-right axis. Thus the left-right reversal of mirror images essentially does not involve psychological processes, in contrast to the multiprocess hypothesis recently proposed by Takano.

Humans↗
PubMed1999

A zinc-dependent Cl- current in neuronal somata.

Extracellular Zn2+ modulates current passage through voltage- and neurotransmitter-gated ion channels, at concentrations less than, or near, those produced by release at certain synapses. Electrophysiological effects of cytoplasmic Zn2+ are less well understood, and effects have been observed at concentrations that are orders of magnitude greater than those found in resting and stimulated neurons. To examine whether and how neurons are affected by lower levels of cytoplasmic Zn2+, we tested the effect of Zn2+-selective chelators, Zn2+-preferring ionophores, and exogenous Zn2+ on neuronal somata during whole-cell patch-clamp recordings. We report here that cytoplasmic zinc facilitates the downward regulation of a background Cl- conductance by an endogenous protein kinase C (PKC) in fish retinal ganglion cell somata and that this regulation is maintained if nanomolar levels of free Zn2+ are available. This regulation has not been described previously in any tissue, as other Cl- currents have been described as reduced by PKC alone, reduced by Zn2+ alone, or reduced by both independently. Moreover, control of cation currents by a zinc-dependent PKC has not been reported previously. The regulation we have observed thus provides the first electrophysiological measurements consistent with biochemical measurements of zinc-dependent PKC activity in other systems. These results suggest that contributions of background Cl- conductances to electrical properties of neurons are susceptible to modulation.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗
PubMed1999

brinker is a target of Dpp in Drosophila that negatively regulates Dpp-dependent genes.

Growth and patterning of the Drosophila wing is controlled in part by the long-range organizing activities of the Decapentaplegic protein (Dpp). Dpp is synthesized by cells that line the anterior side of the anterior/posterior compartment border of the wing imaginal disc. From this source, Dpp is thought to generate a concentration gradient that patterns both anterior and posterior compartments. Among the gene targets that it regulates are optomotor blind (omb), spalt (sal), and daughters against dpp (dad). We report here the molecular cloning of brinker (brk), and show that brk expression is repressed by dpp. brk encodes, a protein that negatively regulates Dpp-dependent genes. Expression of brk in Xenopus embryos indicates that brk can also repress the targets of a vertebrate homologue of Dpp, bone morphogenetic protein 4 (BMP-4). The evolutionary conservation of Brk function underscores the importance of its negative role in proportioning Dpp activity.

Amino Acid Sequence↗
PubMed1999

Clinical implications of coinfection with a novel DNA virus (TTV) in hepatitis C virus carriers on maintenance hemodialysis.

A novel hepatitis-associated DNA virus, designated as transfusion-transmitted virus (TTV), was identified recently. We investigated the frequency of TTV viremia in hepatitis C virus (HCV) carriers on maintenance hemodialysis to determine whether TTV coinfection has any clinical relevance. The subjects were 50 hemodialysis patients who had been followed over 4 years after diagnosis of HCV infection. Stored serum samples derived from each patient every 12th month after enrollment were subjected to polymerase chain reaction to amplify TTV DNA and HCV RNA. At enrollment, TTV viremia was detected in 24 (48%) HCV-positive patients irrespective of the number of previous blood transfusions and the duration of hemodialysis. The presence of TTV viremia had no relation to serum alanine aminotransferase (ALT) levels, HCV viremic levels or HCV genotypes. After enrollment, HCV infection persisted in all patients over the 4-year follow-up period, whereas spontaneous resolution of TTV infection was observed in 7 (29%) of the 24 TTV viremic cases (annual rate 7.3%, 95% confidence interval [CI] 0.8-25.5%). Evidence for TTV infection was found in 4 (15%) of the 26 TTV nonviremic patients (annual incidence 3.9%, 95% CI 0.1-19. 6%). The relationship between the ALT profile and TTV infection during follow up was not evident. Active TTV coinfection occurs frequently in HCV carriers undergoing hemodialysis but exerts no biochemical or virological influence on the underlying hepatitis C. Lack of disease association and the frequent spontaneous resolution of infection suggest that the clinical significance of TTV infection remains unclear.

Adult↗
PubMed1999

Assessment of the revised International Federation of Gynecology and obstetrics staging for early invasive squamous cervical cancer.

OBJECTIVE: The aim of this study was to investigate the value of the International Federation of Obstetrics and Gynecology (FIGO) classification (1995) for early invasive cervical cancer. Methods. Clinico-pathological analysis was performed in 402 patients with invasive squamous cervical cancer in whom the depth of stromal invasion was 5 mm or less. RESULTS: The incidence of lymph node metastasis was 1.2% (1/82) in patients with 3 mm or less depth of invasion; the node-positive patient was in stage IA1. The incidence of lymph node metastasis was 6.8% (5/73) in patients with 3-5 mm depth of invasion; this increased with increasing horizontal spread from 3.4% for 7 mm or less to 9.1% for more than 7 mm. None of the patients in this series had metastasis to the parametrial tissues. Of 4 patients with recurrence, 3 had horizontal spread of more than 7 mm and the remaining patient was in stage IA2. CONCLUSION: The FIGO definition of early squamous cervical cancer is generally acceptable in its present form.

Adult↗
PubMed1999

Low-grade endometrial stromal sarcoma with cardiovascular involvement--a report of three cases.

BACKGROUND: In low-grade endometrial stromal sarcoma, it has been reported that vascular space involvement in surgical specimens is found in over 50% of patients. However, in contrast to intravenous leiomyomatosis, it has been thought that further tumor extension to large vessels is rarely observed. CASES: We present three cases of low-grade endometrial stromal sarcoma with cardiovascular involvement by recurrent tumors observed on imaging studies. Two cases demonstrated tumor infiltration inside the inferior vena cava while the other case showed tumor growth in the left ventricle. CONCLUSION: This report suggests that attention should be paid to the possibility of cardiovascular invasion during the entire course of this disease.

Adult↗
PubMed1999

Functional evaluations for pulmonary resection for lung cancer in octogenarians. Investigation from postoperative complications.

We have reviewed the records of our twenty-four patients aged 80 years or older who underwent lung resections for bronchogenic carcinoma between 1983 and 1997 in our department. Eighteen patients were male and six were female. Adenocarcinoma was the histology in more than half of the cases (13 patients), along with 8 squamous cell carcinoma, 2 large cell carcinoma, and one small cell lung carcinoma. More than single lobectomy was performed in each patient. Unilateral pulmonary occlusion tests were employed in patients with impairment in pulmonary functions. Every patient, who underwent the unilateral pulmonary occlusion test, was certified that the total pulmonary vascular resistance index during unilateral pulmonary arterial occlusion test was less than 700 dyne.sec.cm-5.m2. Postoperative cardiovascular complications, such as paroxysmal atrial tachycardia, premature atrial contraction, premature ventricular contraction or atrial fibrillation, were seen in 10 patients. Postoperative respiratory complications, namely, sputa retention, retained secretions or atelectasis, were seen in 7 patients. The extent of dissection of mediastinal lymph node was not correlated to the postoperative pulmonary complications. However, the incidence of arrhythmias in the patients who received R2 mediastinal lymphnode dissection was much higher than in those who received R1 or R0 dissection. Complete blood counts and serum biochemical analysis performed at about three weeks after operations revealed leukocytosis and increases in levels of serum transaminase. These phenomena in leukocytosis and increases in the levels of serum transaminase in these patients were similar to those in younger patients. There was no operative death. We conclude that some patients over 80 years are candidates for lung resection after careful preoperative cardiopulmonary evaluation.

Adenocarcinoma↗
PubMed1999

Th2 subset dominance among peripheral blood T lymphocytes in patients with digestive cancers.

BACKGROUND: Two types of helper T cells (Th), which are categorized as Th1 and Th2 on the basis of cytokine production, have been reported. Th1 cells produce interleukin (IL)-2 and interferon (IFN)-gamma, while Th2 cells secrete IL-4, IL-6, and IL-10. We assessed the intracellular cytokine profiles of CD3/CD4 positive lymphocytes (CD4+ T-cells) in peripheral blood in patients with digestive cancers. METHODS: Peripheral blood samples were collected from 50 patients with digestive cancers and 35 healthy volunteers. The proportions of CD4+ T-cells producing intracellular cytokines were determined using flow cytometry. RESULTS: The percentages (mean +/- SD) of CD4+ T-cells producing IL-4, IL-6, and IL-10 in the cancer group (73.9% +/- 13.0%, 73.0% +/- 16.6%, and 58.0% +/- 21.0%, respectively) were significantly higher than in the healthy group (37.4% +/- 12.4%, 37.8% +/- 13.5%, and 34.0% +/- 14.1%, respectively; P <0.01). Proportions of CD4+ T-cells producing IL-4, IL-6, and IL-10 in 10 patients undergoing curative resection had decreased significantly 1 month after surgery (P <0.01). No significant difference was noted between groups in the percentages of CD4+ T-cells producing IFN-gamma. CONCLUSIONS: Th2-dominant status develops in cancer patients. Such lymphocyte evaluations could find applications in diagnosis and therapeutic monitoring of cancer patients.

Adult↗